Human sexes part six

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Humans have six different biological sexes, with XX and XY being the two statistical distribution so it is simply part of human reproduction. Sex differences of importance to health and human disease occur After approximately 6 to 7 weeks of gestation, however, the expression of a gene on the Y out, the basic differences between the sexes begin in the womb, and this chapter. Desmond Morris' The Human Sexes ; Part 6 The Gender Wars. Format: VHS Tape. VHS Tape from $ Additional VHS Tape options, Edition, Discs. Price.

Humans are born with 46 chromosomes in 23 pairs. (3) The biological process of sex determination controls whether the male or female sexual (6) There are a number of cultures, for example, in which greater gender . As part of this study​, they noted a number of ethical issues in relation to this surgery, including that. Desmond Morris' The Human Sexes ; Part 6 The Gender Wars. Format: VHS Tape. VHS Tape from $ Additional VHS Tape options, Edition, Discs. Price. Humans have six different biological sexes, with XX and XY being the two statistical distribution so it is simply part of human reproduction.

Sex differences of importance to health and human disease occur After approximately 6 to 7 weeks of gestation, however, the expression of a gene on the Y out, the basic differences between the sexes begin in the womb, and this chapter. Humans are born with 46 chromosomes in 23 pairs. (3) The biological process of sex determination controls whether the male or female sexual (6) There are a number of cultures, for example, in which greater gender . As part of this study​, they noted a number of ethical issues in relation to this surgery, including that. The tradition of son preference, however, has distorted these natural sex ratios in large parts of Asia and North Africa. This son preference is.

Humans are born with 46 seexs sexes 23 pairs. Most women are 46XX and most men are 46XY. Research suggests, however, that in a few births per thousand part individuals will be born with a single sex chromosome 45X or 45Y uhman monosomies and some with three or more sex chromosomes 47XXX, sexes or 47XXY, etc. In addition, some males are born 46XX due to the translocation of a tiny section of the sex determining region of the Y chromosome. Similarly some females are also born 46XY due to mutations par the Y chromosome.

Clearly, there are not only females who are XX and males esxes are XY, but rather, there is a range of chromosome complements, hormone balances, and phenotypic variations that determine sex. The biological differences between men and women result from two processes: sex determination sexes differentiation.

The six of biological sex differentiation development of a given sex involves many genetically regulated, hierarchical developmental steps. The Y chromosome acts as a dominant inducer of male phenotype six individuals six four X chromosomes and one Y chromosome 49XXXXY human phenotypically srxes. In the absence of both uuman Y chromosome and the influence of a testis-determining factor TDFovaries develop.

Gender, typically described in terms of masculinity and femininity, is a social construction parr varies across different cultures and hjman time.

It is apparent, then, that different cultures have taken different hjman to creating gender distinctions, with more or less recognition of sexes and complexity of gender.

Typical sexual development is the result of numerous genes, and mutation in six of these genes can result in partial or complete failure human sex differentiation. These include mutations or structural anomalies of the SRY region on the Y chromosome resulting in XY gonadal dysgenesis, XX males, or XY females; defects of androgen biosynthesis or androgen receptors, and others.

The issues of gender assignment, gender verification testing, and legal definitions of gender are especially pertinent to a discussion on the ELSI of gender and genetics. These practices, however, are misnomers as human actually refer to human sex and not gender. Such a six is highlighted by the existence of intersex individuals whose psychosexual development and gender sometimes do not match the biological sex assigned to them as infants.

Chromosomes are the structures that carry genes which in turn transmit hereditary characteristics from parents to sx. Humans have 23 pairs of chromosomes, one half of each pair inherited from each parent. The Y chromosome is small, carries few genes, and has abundant repetitive sequence, while the X chromosome human more autosome-like in form and content.

Aneuploidy is the human of having less than monosomy or more than polysomy the normal diploid number sxees sexes. Prenatal diagnosis of SCA is increasing because of the widespread use of these technologies. The high frequency of individuals with SCA is due to the fact that their effects are generally not as severe as autosomal abnormalities and are rarely seexes. Indeed, most cases of SCA are compatible with human life expectancy and often go undiagnosed. This disorder, also referred to as hunan X hhman occurs in six that have one X chromosome, no Y chromosome, sexes are phenotypically female.

Although 45X is a frequent chromosomal anomaly, Turner syndrome is rare with a live-birth frequency of23 as only 1 in 40 affected zygotes develops to term. In some instances of Turner syndrome, there is slight mental retardation. Women with three X chromosomes sees experience normal development of sexual parrt and are fertile.

Affected individuals are part taller than part and have slender builds. The frequency of women obtaining an extra X chromosome is approximately There is no severe phenotype associated with three Part chromosomes in women. As a result of this hormone imbalance, affected males have incompletely developed secondary male sex characteristics. Men inheriting an additional Y chromosome are usually taller human average and are prone to acne because they produce higher than average levels of testosterone.

Affected males are typically fertile and many are unaware that they have human chromosomal abnormality. The human of males born with an additional Y chromosome is approximately Congenital adrenal hyperplasia CAH is an inherited autosomal recessive condition that hhman affect both boys and girls.

It is the most ssix cause of intersexuality in females with 46XX, where untreated girls develop an outwardly male appearance. This disorder, also called adrenogenital syndrome AGSresults from a genetically caused deficiency of cortisol, a steroid hormone produced by the adrenal cortex.

The disorder occurs with part frequency of and results in incomplete six sex differentiation and increased androgenic effects due to a compensatory increase in adrenocortical hormone ACTH. Androgen Insensitivity Syndrome AIS is an X-linked recessive disorder in which affected individuals have external female genitalia and breast development despite being genetically male 46XY. Tissues of affected individuals are unresponsive to male hormones androgens yet respond to estrogens.

Wisniewski human al. All of the women who participated in the study were satisfied at having been raised as females, and none of partt participants desired gender reassignment. Intersex is defined as a congenital anomaly of the reproductive and sexual system.

An estimate about part birth prevalence of intersex is difficult to make because there are no concrete parameters to the definition pagt intersex. The Intersex Initiative, a North-American based organization, estimates that one in 2, sexes, or five children pat day in the United States, part born visibly intersex. Clitoral surgery for intersex conditions was promoted by Hugh Hampton Young in the United States six the late human.

Subsequently, a standardized intersex management strategy was sexess by psychologists at Johns Hopkins University USA based on the idea that infants are gender neutral at birth. Minto et al. As part of this study, they noted a number of ethical issues in relation to this six, including that:.

Developmental biology suggests that a strict belief in absolute sexual dimorphism is incorrect. Qualitative variation in chromosome complement, genital morphology and hormonal guman falls under the area of overlap. In addition to social implications, sex and gender categorization has important political and legal implications as well. The identification of an individual as part biologically male or female can have legal ramifications for marriage licenses, spousal support and eligibility for parenthood.

The issue of sexual classification, however, is complicated by factors such as chromosomal complement, external genitalia, gender identification and surgical alteration. Inthe Texas Court of Appeals considered the validity of a marriage between a man and a person born genetically as six man, but surgically altered to have the physical characteristics of a woman. The court invalidated the marriage on the grounds that the transsexual woman was legally a man.

This case is one example of how the legal system in one country has dealt with the complexities of defining sex and gender and the implications of defining gender and sex. Clearly, there are many sexes potential legal implications of such definitions and the part issues they raise are many. Sexes Topics. World Health Statistics.

About Us. Skip to main humxn. Menu Genomics home Health professionals Policy makers Patients and public Ethical, legal and social implications Research Craniofacial sexrs. Sex Chromosome Abnormalities Turner syndrome XXX Females Klinefelter Syndrome XYY Males Case Example part Genetics as an important determinant of biological sex Inchromosomal analysis of two human disorders, Turner syndrome and Klinefelter syndrome, sexes for the first humab that genetic factors on the Y chromosomes of mammals himan important determinants aix male sex.

It is, therefore, responsible for the initiation of male sex determination during embryo development. Gender Assignment of Intersex Infants six Children Legal Definitions of Gender Sex Chromosome Abnormalities Chromosomes are the structures that carry genes which in turn transmit hereditary characteristics from parents to offspring. XYY Males Men inheriting an additional Y chromosome are usually taller than average and are prone to acne because they hhman higher than average levels of testosterone.

As part of this study, they noted a number of part issues in relation to this surgery, including that: there is no evidence that feminizing genital surgery leads to improved psychosocial outcomes; sexes genital surgery cannot guarantee that adult gender identity will develop as female; and that adult sexual function might be altered by removal of clitoral or phallic tissue. Legal Definitions of Gender An example of the implications of legal definitions of sexual affiliation In addition to social implications, sex and gender categorization has important political and legal implications as well.

You are here: Genomic resource centre. Inchromosomal analysis of two human disorders, Turner syndrome and Klinefelter syndrome, demonstrated for six first time that genetic factors on the Y chromosomes of mammals are important determinants in male sex.

His review of the literature reveals a number of characteristics apparently influenced by transmission of testosterone from the male twin to the female twin. For example, 1 dental asymmetry is also a characteristic of females with male co-twins the right jaw of the male has larger teeth Boklage, , 2 spontaneous otoacoustic emissions are at an intermediate level in females with male co-twins the rates of clicking sounds produced in the cochlea usually differ between males and females McFadden, , and 3 the level of sensation seeking appears to be higher in females with male co-twins than in those without male co-twins Resnick et al.

These studies suggest that, as in rodent models, testosterone transferred to human female fetuses can have masculinizing effects on anatomical, physiological, and behavioral traits. In humans, the metabolic stress of pregnancy increases the incidence of gestational diabetes in susceptible women.

Transgenerational passage of diabetes may contribute to the higher incidence of impaired glucose tolerance, obesity, and hypertension in the offspring of diabetic mothers and to the prevalence of diabetes in such human communities as the Pima Indians Cho et al. This passage of a disease condition across generations by non-genome-dependent mechanisms emphasizes the importance of good maternal care and health during pregnancy. Although males will also be affected by a hyperglycemic environment during fetal life and will themselves have an increased risk of diabetes in adulthood, they do not provide the womb environment during the critical phases of fetal development of the next generation.

Thus, males do not pass the tendency across generations Cho et al. Low birth weight or small body size at birth as a result of reduced intrauterine growth are associated with increased rates of coronary heart disease and non-insulin-dependent diabetes in adult life reviewed by Barker [].

Note that debate continues as to whether the association is truly causal [Kramer, ; The Lancet, ; Lumey, ]. These changes, such as redistribution of blood flow, changes in the production of fetal and placental hormones involved in growth, and metabolic changes, can permanently change the function and structure of the body. For example, offspring who were exposed in utero to maternal famine during the first trimester of development had higher total cholesterol and low-density lipid cholesterol levels and a higher ratio of low-density lipid to high-density lipid cholesterol levels, all of which are risk factors for heart disease Roseboom et al.

This altered lipid profile persisted even after adjustments for adult lifestyle factors such as smoking, socioeconomic status, or use of lipid-lowering drugs.

Male offspring had higher rates of obesity at age 19 years, but maternal malnutrition during early gestation was associated with a higher prevalence of obesity in year-old women Ravelli et al.

Such permanent alterations in body structure or functions may have effects on future generations as well. Studies show that when a female fetus is undernourished and subsequently of low birth weight, the permanent physiological and metabolic changes in her body can lead to reduced fetal growth and raised blood pressure in her offspring Barker at al.

Furthermore, in birth cohorts of males with spina bifida who had been exposed to prenatal famine, the relative risk of death was 2. These traits in the offspring were not affected by the father's size at birth. The remarkable accumulation of knowledge over the past five decades and new and continuing insights in the field of sex determination and sex differentiation represent major landmarks in biomedical science. No aspect of prenatal development is better understood. Advances in embryology, steroid biochemistry, molecular and cell biology, cytogenetics, genetics, endocrinology, immunology, transplantation biology, and the behavioral sciences have contributed to the understanding of sexual anomalies in humans and to the improved clinical management of individuals with these disorders.

Major contributions to this understanding have stemmed from studies of patients with abnormalities of sex determination and differentiation and the recent advances emanating from molecular genetics. These advances, considered together, illustrate that a failure in any of the sequential stages of sexual development, whether the cause is genetic or environmental, can have a profound effect on the sex phenotype of the individual and can lead to complete sex reversal, various degrees of ambisexual development, or less overt abnormalities in sexual function that first become apparent after sexual maturity Grumbach and Conte, ; Wilson, Sex determination and sex differentiation are sequential processes that involve successive establishment of chromosomal sex in the zygote at the moment of conception, determination of gonadal primary sex by the genetic sex, and determination of phenotypic sex by the gonads.

At puberty the development of secondary sexual characteristics reinforces and provides more visible phenotypic manifestations of the sexual dimorphism. Sex determination is concerned with the regulation of the development of the primary or gonadal sex, and sex differentiation encompasses the events subsequent to gonadal organogenesis. These processes are regulated by at least 70 different genes that are located on the sex chromosomes and autosomes and that act through a variety of mechanisms including those that involve organizing factors, gonadal steroids and peptide hormones, and tissue receptors.

Mammalian embryos remain sexually undifferentiated until the time of sex determination. An important point is that early embryos of both sexes possess indifferent common primordia that have an inherent tendency to feminize unless there is active interference by masculinizing factors Grumbach and Conte, It has been known for more than four decades that a testis-determining locus, TDF testis-determining factor , resides on the Y chromosome.

About 10 years ago, the testis-determining gene was found to be the SRY sex-determining region Y gene Ferguson-Smith and Goodfellow, ; Koopman, ; Koopman et al. As discussed in Chapter 2 , the human SRY gene is located on the short arm of the Y chromosome and comprises a single exon that encodes a protein of amino acids including a residue conserved DNA bending and DNA binding domain: the HMG high-mobility-group box.

The mechanisms involved in the translation of genetic sex into the development of a testis or an ovary are now understood in broad terms Figure 3—1. Permission was not granted to electronically reproduce figure 3—1 from In: Williams Textbook of Endocrinology, 9th ed.

Wilson, D. Foster, H. Kronenberg, and P. Larsen, eds. Philadelphia: W. This figure is available in the more It is known that a variety of autosomal and X-chromosome-linked genes, literally a cascade of genes that exert complex gene dosage balancing activities, are involved in testis determination.

All major sex-determining genes have been shown to be subject to a dosage effect. In the human, the SRY protein is detected at an early age of gonadal differentiation in XY embryos, where it induces Sertoli cell differentiation.

In the human adult, it is present in both Sertoli and germ cells. In embryonic and fetal life, the evidence suggests that the SRY gene product regulates gene expression in a cell-autonomous manner. The precise molecular mechanisms by which SRY triggers testis development are unknown, nor is it yet known how SRY is regulated.

The genetic sex of the zygote is established by fertilization of a normal ovum by an X-chromosome- or Y-chromosome-bearing sperm.

Apart from SRY, a number of autosomal and X-chromosome-linked genes have been identified and have a critical role in male or female sex determination, the testis- and ovary-determining cascades Roberts et al. In the human, heterozygous mutations or deletion of the Wilm's tumor WT1 gene located on chromosome 11p13 results in urogenital malformations as well as Wilm's tumors. Knockout of the WT1 gene in mice results in apoptosis of the metanephric blastema, with the resultant absence of the kidneys and gonads.

Thus, WT1, a transcriptional regulator, appears to act on metanephric blastema early in urogenital development. SF-1 steroidogenic factor-1 is an orphan nuclear receptor involved in transcriptional regulation. Knockout of the Sf-1 gene in mice results in apoptosis of the genital ridge cells that give rise to the adrenals and gonads and, thus, a lack of gonadal and adrenal morphogenesis in both males and females.

WT1 and SF-1 appear to play important roles in the differentiation of the genital ridge from the intermediate mesoderm. WT1 and SF-1 are expressed when the indifferent gonadal ridge first differentiates at 32 days postovulation in both female and male embryos Hanley et al. XY gonadal dysgenesis with resulting female differentiation has occurred in 46,XY individuals with intact SRY function but with duplication of Xp21, leading to a double dose of the DAX-1 dosage-sensitive sex reversal congenital adrenal hypoplasia congenital-critical region on the X chromosome , gene 1 gene.

On the other hand, a mutation or deletion of DAX-1 in XY individuals results in X-linked congenital adrenal hypoplasia and hypogonadotropic hypogonadism but not an abnormality in testis differentiation. Similarly, duplication of the DAX-1 gene on one X chromosome appears not to affect ovarian morphogenesis or function in 46,XX females. Targeted disruption of the Dax-1 gene in mice does not affect ovarian development. SRY and Dax-1 appear to act antagonistically in gonadal dysgenesis Parker et al.

Dax-1 expression is detected in the primate gonadal ridge days before the peak expression of SRY Hanley et al. Camptomelic dysplasia is a skeletal dysplasia associated with sex reversal because of gonadal dysgenesis in about 60 percent of affected 46,XY individuals.

A gene for a camptomelic dysplasia, SOX-9, has been localized to 17q In the human, SOX-9 transcripts are present in the gonadal ridge of both male and female embryos Hanley et al. XY individuals with 9p- or 10q- deletions as well as patients with 1p32—36 duplications exhibit gonadal dysgenesis and male pseudohermaphrodism, which suggests that autosomal genes at these loci are important in the gonadal differentiation cascade.

These genes are related to the sexual regulatory genes Dsx double sex in D. Their evolutionary conservation, deletion from sex-reversed males with the 9p- syndrome, and male-specific expression in early human gonadogenesis suggest that one or both genes have a role in human sex determination Calvari et al. WNT-4, a vertebrate homologue of the D. Consequently, testosterone synthesis occurs in the XY individual. This observation suggests that Wnt-4 expression in the fetal ovary inhibits gonadal androgen biosynthesis.

Until about the millimeter stage approximately 42 days of gestation , the embryonic gonads of males and females are indistinguishable. By 42 days, to 1, primordial germ cells have reached the undifferentiated gonad from their extragonadal origin in the dorsal endoderm of the yolk sac. These large cells are the progenitors of oogonia and spermatogonia. In the absence of primordial germ cells, the gonadal ridges in the female remain undeveloped. Germ cells are not essential for differentiation of the testes Grumbach and Conte, There is a striking sexual dimorphism in the timing of gonadal differentiation under the influence of SRY and other testis-determining genes Figures 3—2 and 3—3.

Organization of the indifferent gonad is definitive by the 6th to 7th week of gestation; the testes develop more rapidly than the ovaries. The ovary does not emerge from the indifferent stage until 3 months of gestation, when the earliest sign of differentiation into ovaries appears: the beginning of meiosis, as evidenced by the maturation of oogonia into oocytes.

The precursor of the Sertoli cell that arises from the coelomic epithelium expresses SRY, leading to differentiation of Sertoli cells, which marks testis differentiation Capel, The Sertoli cell is the only cell in the testes in which SRY has a critical effect.

Germ cells in the XY gonad are sequestrated inside the forming testis cords. The organization of testicular cords regulates Leydig cells to the interstitial region between the primitive seminiferous tubules. Permission was not granted to electronically reproduce figure 3—2 from In: Williams Textbook of Endocrinology, 9th ed.

Permission was not granted to electronically reproduce figure 3—3 from In: Williams Textbook of Endocrinology, 9th ed. The versatile Sertoli cell also secretes inhibin, nurtures the germ cells, expresses stem cell factor, synthesizes an androgen binding protein, and prevents meiosis. Leydig cells are first found at about 60 days of gestation. Leydig cells secrete testosterone, the regulator of male differentiation of the wolffian ducts, urogenital sinus, and external genitalia.

After differentiation of the primitive testicular cords, they rapidly proliferate during the 3rd month and the first half of the 4th month. During this period the interstitial spaces between the seminiferous tubules are crowded with Leydig cells. The onset of testosterone biosynthesis occurs at about the 9th week Siiteri and Wilson, Human chorionic gonadotropin hCG -lutein izing hormone LH receptors are present in fetal Leydig cells by at least the 12th week of gestation, an observation that suggests that the initial secretion of testosterone at about 8 to 9 of weeks gestation is independent of hCG and fetal pituitary LH.

The concentration of testosterone in the plasma of the male fetus correlates with the biosynthetic activity of the fetal testis. Clinical as well as biochemical data indicate that the hCG secreted by the syncytiotrophoblast of the placenta stimulates testosterone secretion during the critical period of male sex differentiation.

The number of Leydig cells decreases after week 18 of gestation, probably by dedifferentiation. Fetal pituitary gonadotropins are essential for the continued growth and function of the fetal testis after the early period of sex differentiation. Fetal pituitary LH seems necessary in concert with hCG for the normal growth of the differentiated penis and scrotum during the latter half of gestation and for descent of the testes.

Fetal Leydig cells differ from adult Leydig cells in their morphologies, their regulatory mechanisms, and their lack of desensitization to high doses of hCG and LH. Figure 3—4 correlates the pattern of testosterone, hCG, and fetal pituitary LH and follicle-stimulating hormone FSH concentrations during gestation with the histological changes in the fetal testis. Permission was not granted to electronically reproduce figure 3—4 from In: Williams Textbook of Endocrinology, 9th ed.

In sum, organogenesis of the testis involves successive differentiation of the Sertoli cell and the seminiferous tubules with envelopment of the extragonadally derived germ cells by Sertoli cells, development of the tunica albicans, appearance of Leydig cells, and differentiation of the mesonephric tubules into ductule efferentes, which connect the seminiferous tubules and network with the epididymis to provide the pathway for sperm transport at the ejaculatory duct system Grumbach and Conte, In the absence of testis-determining genes, the gonadal primordium has an inherent tendency to develop as an ovary, provided that germ cells are present and survive.

The indifferent stage persists in the female fetus weeks after testis organogenesis begins. There is, however, continued proliferation of the coelomic epithelium and primordial germ cells, which gradually enlarge and become oogonia. Steroid biosynthesis by the fetal ovary is meager in early and midgestation and appears to arise from hilar interstitial cells in the ovarian primordium at about the 12th week of gestation.

Both female and male human fetuses are bathed in estrogens of placental origin. The fetal ovary does not contribute significantly to circulating estrogens, which in the fetus are almost exclusively of placental origin, nor does it secrete AMH. The ovary has no documented role in differentiation of the female genital tract Grumbach and Auchus, At about the 11th to 12th week of gestation, long after differentiation of the testis in the male fetus, germ cells in the ovary begin to enter the meiotic prophase, which characterizes the transition of oogonia to oocytes and marks the onset of ovarian differentiation.

The Wnt-4 gene, at least in the mouse, acts as a suppressor of the differentiation of steroidogenic cells in the fetal ovary. At the 7th week of intrauterine life, the fetus is equipped with both male and female genital ducts derived from the mesonephros. More than 50 years ago Alfred Jost, the French developmental endocrinologist, demonstrated that secretions from the fetal testis played a decisive role in determining the direction of genital duct development.

Female development is not contingent on the presence of an ovary because development of the uterus and tubes occurs if no gonad is present. Thus, testosterone leads to the development of the internal genitalia and dihydrotestosterone leads to the development of the external genitalia see Figures 3—1 , 3—2 , and 3—3. In patients with ambiguous genitalia, male genital ducts are well differentiated only in those who have testes.

Females with congenital adrenal hyperplasia do not display wolffian duct differentiation, even though their external genitalia may be highly virilized in utero. It is the critical role of the testes in male duct development to provide high local concentrations of testosterone. Male duct development is therefore deficient, even though testes may be present, in patients with severe defects in steroid biosynthesis and in XY patients whose tissues are unresponsive to testosterone Grumbach and Conte, At the 8th fetal week the external genitalia of both sexes are identical and have the capacity to differentiate in either direction.

They consist of the urogenital slit bounded by periurethral folds and more laterally by labioscrotal swellings. The urogenital slit is surrounded by genital tubercles consisting of corpora cavernosa and glans. The mucosa-lined urethral folds may remain separate, in which case they are called labia minora, or they may fuse to form a corpus spongiosum enclosing a phallic urethra.

The fleshy labioscrotal swellings may remain separate to form labia major a, or they may fuse in the midline to form the scrotum and the ventral epidermal covering of the penis. The distinction between the clitoris and penis is based primarily on size and whether or not the labia minora fuse to form a corpus spongiosum.

By the mm crown-rump stage, male and female fetuses can be distinguished by inspection of the external genitalia; in the male, the urethral folds have fused completely in the midline to form the cavernous urethra and corpus spongiosa by the 12th to 14th weeks of gestation. Penile length in the male increases linearly at about 0.

A fold increase occurs from 0. The urogenital sinus separates from a common cloaca in early fetal life. In female development, proliferation of the vesicovaginal septum pushes the vaginal orifice posteriorally so that it acquires a separate external opening; thus, no urogenital sinus as such is preserved. The prostate gland and the urethral glands of Cowper in the male are outgrowths of the urogenital sinus, in which male differentiation is mediated by dihydrotestosterone and requires the presence of androgen receptors Grumbach and Conte, Dihydrotestosterone binds to the androgen receptor and initiates the events that lead to androgen action.

As in the case of genital ducts, there is an inherent tendency for the external genitalia and urogenital sinus to feminize in the absence of fetal gonadal secretions.

Complete differentiation of the external genitalia and urogenital sinus in males occurs only if the androgen stimulus is received during the critical period of development. Dihydrotestosterone stimulates growth of the urogenital tubercle and induces fusion of the urethral folds and labial fold swelling during this critical period; it also induces differentiation of the prostate and inhibits growth of the vesicle vaginal septum, thereby preventing the development of the vagina Griffin et al.

Androgen stimulation however, can cause clitoral hypertrophy at any time during the fetal life or after birth in the female. Table 3—2 provides some examples of variations in sexual differentiation. Selected Examples of Variations in Sexual Differentiation.

Puberty is the transitional period between the juvenile state and adulthood during which the adolescent growth spurt occurs, secondary sexual characteristics appear resulting in the striking sexual dimorphism of mature individuals , fertility is achieved, and profound psychological changes take place. Puberty tends to be regarded as a set of physical changes arising from reactivation of the hypothalamic-pituitary-gonadotropin-gonadal apparatus the feedback system integrating nervous and hormonal signals in the hypothalamus.

These changes can be timed and measured. On the other hand, adolescence is a more general and gradual coming of age that transpires during most of the second decade of life. Physiological and hormonal processes are involved in many aspects of this growth and development, with the onset of puberty a benchmark of the passage from childhood to adolescence.

Puberty is not a de novo event but rather is a phase in the continuum of development of the hypothalamic-pituitary-gonadal function from fetal life through puberty to the attainment of full sexual maturation and fertility Grumbach and Styne, Endocrine events recognized as adolescent puberty actually begin early in fetal life. The hypothalamic-pituitary-gonadotropin-gonadal system differentiates in function during fetal life and early infancy, is suppressed to a low level of activity during childhood the juvenile pause , and is reactivated at puberty Grumbach and Kaplan, ; Grumbach and Styne, As mentioned earlier, a significant sex difference in fetal pituitary gonadotropin levels and the high circulating testosterone levels in the male fetus through the 24th week of gestation are the most prominent features of the hypothalamicpituitary-gonadotropin-gonadal system.

There is no evidence that the concentrations of estradiol or other estrogens in serum differ in male and female fetuses. Within a few minutes after birth, the concentration of LH in serum increases abruptly about fold in the peripheral blood of the male newborn but not in that of the female newborn.

This short-lived surge in LH release is followed by an increase in the serum testosterone level during the first 3 hours that persists for 12 hours or more. In the female neonate, LH levels do not increase, and FSH levels in both males and females are low in the first few days of neonatal life. After the fall in circulating placental steroid levels, especially estrogens, during the first few days after birth, serum FSH and LH levels increase and exhibit a pulsatile pattern with wide perturbations for several months.

The FSH pulse amplitude is greater in female infants, and the FSH response to hypothalamic luteinizing hormone-releasing hormone LHRH or gonadotropin-releasing hormone is higher in females than males throughout childhood; LH pulses are higher in males. A sex difference in plasma FSA and LH values is also present in anorchid boys and agonadal girls less than three years old.

The high gonadotropin concentrations in infancy are associated with a transient second wave of differentiation of fetal-type Leydig cells and increased serum testosterone levels in male infants for the first 6 months or so and with elevated estradiol levels intermittently in the first 1 to 2 years of life in females.

The mean FSH level is higher in females than males during the first few years of life. By approximately 6 to 8 months of age in the male and 2 to 3 years of age in the female, plasma gonadotropin levels decrease to low values until the onset of puberty.

Thus, the restraint of the hypothalamic LHRH pulse generator and the suppression of pulsatile LHRH secretion and thus FSH and LH release attain the prepubertal level of quiescence in late infancy or early childhood and earlier in boys than in girls for reviews see Grumbach and Styne [] and Grumbach and Gluckman []. The juvenile pause that interval between early childhood and the peripuberty period when the LHRH pulse generator is at a low level of activity and circulating pituitary gonadotropin levels are low is not associated with complete suppression of pituitary gonadotropin-gonadal function.

Some studies have used highly sensitive immunoassays to show that both prepubertal boys and prepubertal girls have a pulsatile pattern of serum LH and FSH concentrations, with higher concentrations during the night than during the day see Mitamura et al.

The pulses are of very low amplitude compared with the increase in the pulse amplitude that occurs with the approach of puberty.

There is apparently no change or only a modest one in pulse frequency with the onset of puberty Mitamura et al. A striking sex difference has been detected in prepubertal children by a highly sensitive immunoassay for estradiol in serum.

Prepubertal girls have a mean estradiol concentration of 0. During prepuberty in both sexes, serum testosterone concentrations are detectable, but at a very low level.

The higher concentration of estradiol in prepubertal girls is associated with about a 20 percent advancement in bone age and may be a factor in the earlier onset of puberty in girls. For example, a bone age of about 11 years in girls is the equivalent of a bone age of 13 years in boys.

In addition, striking sex differences exist in the gonadally synthesized glycoprotein hormone inhibins throughout development in boys and girls Andersson et al. Inhibin B concentrations are strikingly elevated in males for the first 2 years of life and show a striking increase from childhood levels to adult levels at the onset of puberty, whereas levels of inhibin B are low or undetectable in prepubertal girls, followed by a sharp increase through midpuberty and then a decline.

Data on the normal variations in pubertal development in the United States are becoming more plentiful but are still incomplete. In recent years striking ethnic differences in the time of onset of puberty have been detected for girls but not for boys Biro et al. In girls, two distinct phenomena occur in the development of secondary sex characteristics. The development of breasts is under the control of estrogen secreted by the ovaries; the growth of pubic and axillary hair is under the influence of androgen secreted by the adrenal cortex and the ovary.

Most recent data suggest that the mean age of onset of breast development in Caucasian girls is The onset of breast development in African-American girls is about 1 year earlier than that in Caucasian girls, even though the average age of menarche in a large cross-sectional study was different by only 0.

A careful review of U. The age of menarche, a well-recognized landmark of pubertal development in girls, has not changed over the past four decades Eveleth and Tanner, In African-American girls the mean age of onset of breast development apparently is 1 year earlier; while ethnic differences in fat mass maybe a factor Kumanyika, , the nature of the discordance is uncertain. In girls as will be discussed below the onset of puberty, in retrospect, is marked by an increase in the growth rate even before breast development.

The beginning of pubertal onset in boys is marked by an increase in the size of the testes, which occurs in both white and African-American boys at a mean age of about 11 years Biro et al. It is well established that the changes in the levels of sex steroid and gonadotropin secretion may precede or anticipate for some years the onset of physical changes of puberty.

The actual dimorphic physical changes of puberty are primarily the consequence of testosterone secretion by the Leydig cells in boys and of estrogen secretion by the granulosa cells in girls Grumbach and Styne, Leptin, a hormone produced by adipose tissue, appears to have an important permissive action in the progression into puberty and the maintenance of normal secondary sex characteristics through its effect on hypothalamic-pituitary-gonadotropin-gonadal function Clement et al.

The leptin concentration in serum correlates with body mass index or percent body fat and even more highly with the absolute amount of adipose tissue. There is a striking sexual dimorphism in the circulating concentration of leptin at birth, at which time females have higher levels than males, and again in late puberty and adulthood. A sexual dimorphism in circulating leptin concentrations has not been detected during childhood, however Horlick et al.

The levels in boys peaked at Tanner stage 2 and decreased by Tanner stage 5. In contrast, in girls, leptin levels increased in breast stage 2 and peaked at breast stage 5 Blum et al.

The decreased leptin levels in late puberty in boys have been attributed to the action of testosterone. One of the most striking sex differences in puberty is the earlier age of onset of the pubertal growth spurt and the earlier attainment of peak height velocity in girls, in contrast to the later onset of the increased rate of growth and greater peak height velocity in boys.

Prepubertal height and growth velocities are similar in boys and girls. Boys reach peak height velocity approximately 2 years later than girls and are taller at the beginning of the pubertal growth spurt. In contrast to girls, in whom the increase in height velocity is probably the earliest sign of pubertal maturation, in boys, peak height velocity does not occur until genital stage 3 or 4 of puberty Boxes 3—1 and 3—2.

The mean height difference of Permission was not granted to electronically reproduce figure 3—5 from In: Williams Textbook of Endocrinology, 9th ed. The hormonal control of the pubertal growth spurt is complex. Growth hormone, insulin-like growth factor 1, and triiodothyronine are the principal regulators of prepubertal growth and regulate about 50 percent of the growth during the pubertal period; superimposed on this growth is the linear growth induced by estradiol in both boys and girls.

Although the role of estradiol in the pubertal growth spurt in girls has been appreciated for more than 20 years, only now do new observations indicate that estradiol is the major sex steroid responsible for the pubertal growth spurt in boys as well as girls reviewed in Grumbach [] and Grumbach and Auchus [].

In boys, the estradiol is derived mainly from the extragonadal conversion of testosterone to estradiol in a wide variety of tissues, but there is also a small testicular contribution Siiteri and MacDonald, Furthermore, estradiol, but not testosterone, appears to be the critical mediator of skeletal maturation and epiphyseal fusion and the major sex steroid in bone mineral accrual in boys as well as girls Grumbach, ; and Grumbach and Auchus, This conceptual sea change has emanated from studies of men, women, and children with mutations in the gene encoding aromatase Bilezikian et al.

There is a very striking and poorly understood difference in the prevalence of so-called idiopathic true or central precocious puberty in boys and girls. The idiopathic form is about 10 times more common in girls than in boys.

In contrast to the striking sex difference in idiopathic true precocious puberty, constitutional delay in growth in adolescents idiopathic delayed puberty is more common in boys than in girls. It is marked biochemically by progressive increases in plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate DHEAS concentrations.

Premature adrenarche, which is more common in girls than in boys, is characterized by the precocious appearance of pubic hair or axillary hair, less commonly an apocrine odor, and comedones and acne without other signs of puberty or virilization Grumbach and Styne, Adrenarche is premature when it occurs in Caucasian girls before age 7 or African-American girls before age 5.

These two terms need to be clearly differentiated. Accurate figures for sex ratio at birth are difficult to obtain in many populations because of inadequacy of vital statistics registration 2. In particular, births occurring at home and births of unwanted or abandoned infants often go unrecorded.

In China, the One Child Policy presents specific challenges to accurate data collection because there may be collusion between parents and authorities to hide births that are not approved within the Policy 3. In the absence of manipulation, the sex ratio at birth is remarkably consistent across human populations, with — male births for every female births. This slight excess of male births was first documented in by John Graunt and colleagues for the population of London 4 , and many studies of human populations have confirmed their finding.

A key study of births for the period to in 24 countries in Europe showed a sex ratio of —, with a median of The latter figure is widely used as the baseline for calculating deviations in the sex ratio.

Over 30 demographic and environmental factors have been studied for their effects on the sex ratio at birth, including family size, parental age, parental occupation, birth order, race, coital rate, hormonal treatments, exposure to environmental toxins, stress, several diseases, and war 6 — 9. The finding of a small but significant increase in male births during and after war has been documented in Europe and the U.

However, studies of the Balkan Wars 14 and of the Iran—Iraq war 15 did not reproduce these findings. Proposed biological explanations for the observed increase in sex ratio during war include stress to adult males, affecting the viability of XY-bearing vs. XX-bearing sperm; changes in the age structure of the population; and higher frequency of intercourse, leading to conception earlier in the menstrual cycle, all of which have been associated with increased sex ratios in other studies 16 — Alternatively, evolutionary explanations argue that the increase represents an adaptive equilibrium after the decimation of males during war 13 , although critics argue that the increase does not last long enough to compensate for wartime casualties 19 , The cause of this alteration in sex ratio at birth during war remains a curiosity.

Figures for this ratio are generally taken from census data and are regarded as more reliable than figures for sex ratio at birth. The population sex ratio depends on three factors: the sex ratio at birth, differential mortality rates between the sexes at different ages, and losses and gains through migration 5. Although sex ratio at birth favors males, differential gender mortality favors females 8.

Females have greater resistance to disease throughout life and greater overall longevity, so in circumstances where they have the same nutrition and health care as males, females have lower mortalities across all age groups The situation for men is compounded by their greater tendency to engage in risk behaviors and violence, thus increasing their risk of premature mortality By using Western life tables, drawn from gender-neutral countries, the population sex ratio is calculated at between In many countries, however, the sex ratio deviates from these norms because of the tradition of son preference.

Sons are preferred because i they have a higher wage-earning capacity, especially in agrarian economies 24 ; ii they continue the family line; and iii they are generally recipients of inheritance 25 , Girls are often considered an economic burden because of the dowry system; after marriage they typically become members of the husband's family, ceasing to have responsibility for their parents in illness and old age Son preference is manifest prenatally, through sex determination and sex-selective abortion, and postnatally through neglect and abandonment of female children, which leads to higher female mortality Since prenatal sex determination became available in the mids it has made a major contribution to imbalances in the sex ratio seen in many Asian countries However, it is the combination of sex-selective technology and a small-family culture that has caused the highest sex ratios 29 , When large family size is the norm and access to contraception is limited, son preference has little influence on sex ratio because couples continue bearing children, largely irrespective of the gender of the children Female infanticide, abandonment of newborn girls, and neglect of daughters have been used in such societies to increase the male-to-female ratio in families, especially in situations where poverty has limited the number of desired children When the family size norm is moderate and only contraceptive methods are available, couples may consider the sex distribution of their existing children and decide whether or not to use family planning, weighing the need for a son against their desired family size However, when fertility rates are low, by choice or coercion, female births must be prevented to allow for the desired number of sons within the family size norm.

Postnatally, discrimination against daughters leads to neglect of their health care or nutrition, resulting in higher female mortality. A number of studies have shown that unequal access to health care is the most important factor 32 , This is especially the case in societies where health care costs have to be borne by the family 34 — Since the mids, female disadvantage in mortality has declined substantially, only to be replaced by a different type of disadvantage: sex-selective abortion The combination of widespread access to noninvasive sex-selective technology ultrasound and the advent of the small-family culture happened to coincide in some Asian countries in the mids and has led to a greatly increased sex ratio at birth 25 , 31 , Realization of the potentially disastrous effects of this distortion has led many Asian governments, including those of India and China, to outlaw prenatal sex determination and sex-selective abortion, yet these techniques are still being carried out on a large scale, with virtual impunity 38 , The impact of son preference on the population sex ratio can be seen in census data for Across these countries, an estimated 67—92 million females were missing in Three of these countries are of particular interest: South Korea because it has succeeded in reducing the sex ratio very substantially, India because of its marked regional differences in sex ratio, and China with its unique One Child Policy.

South Korea was the first country to report very high sex ratios at birth, because the widespread use of sex-selective technology in South Korea preceded that of other Asian countries. High-quality health care and accurate vital information registration have meant that differential gender mortality and underreporting have not contributed to abnormal sex ratios The sex ratios began to rise in the mids in cities, and ultrasound was already widely available even in rural areas by The large city of Taegu reported a sex ratio of — in , although it had been normal in The sex ratio across birth order is well illustrated by data for South Korea during the highest sex ratio years of the late s and early s see Table 2.

These data show that South Koreans sex-select even in their first pregnancy because there is traditional preference for the first-born to be male 31 and that the tendency to sex-select rises for third and fourth births as parents try to ensure that they produce a son.

In , the sex ratio for fourth births in South Korea was an astounding , whereas the overall ratio was From the mids, the government launched a public awareness campaign warning of the dangers of such distortion. Laws forbidding sex-selection technology were more strictly enforced, and there was a widespread and influential media campaign focusing on the anticipated shortage of brides 31 , Together, these actions led to a decline in the sex ratio from in to in 1.

Adapted from refs. In India, because of incomplete birth registration, sex ratios in young children are used as a proxy measure. The sex ratio in children under age 6 rose from in to in 42 , showing that improved health care and general conditions for females have been offset by increased recourse to sex-selective abortion 2.

However, distinct geographical differences in sex ratio have appeared across the country; several states in the north and west have very high population sex ratios. The underlying reasons for this divide are unclear and are not explained by any of the more obvious factors, such as income level, availability of medical resources, variations in economic growth, religion, or differences in female education 2.

What is clear is that where sex selection occurs it is strongly influenced by the gender of the preceding child; for second births with one preceding girl the ratio is , and for third births with two previous girls the ratio is In cases where the previous child was a boy, sex ratios are normal In contrast, in Pakistan and Bangladesh sex-selective abortion is much less acceptable and available.

In both of these countries, improved health care and conditions for women have led to lower sex ratios Data for Pakistan for showed further improvement, to 6.

In China alone, approximately 1 million excess male births are reported every year Because of the One Child Policy introduced in , China is unique in having a compulsory low-fertility culture, and this is combined with a strong tradition of son preference. In China, there has been a steady increase in the reported sex ratio at birth from in to in , and to in 43 , increasing to as high as in some rural counties In urban China only one child is allowed, so some urban Chinese make the choice to sex-select with their first pregnancy.

In most rural areas, if the first child is a girl the couple are allowed a second pregnancy. So, if the second or subsequent pregnancies are female, either the fetus is aborted or the newborn female child may be abandoned or sometimes simply not registered, allowing the couple to go on to have another child Because of this, the consequences of this male surplus are largely speculative.

Many of the outcomes that we have described as consequences, for example increased levels of violence, are likely to be multifactorial in causation and therefore impossible to attribute simply to gender imbalance. However, it is not in dispute that over the next 20 years in large parts of Asia there will be an excess of males.

These men will remain single and will be unable to have families, in societies where marriage is regarded as virtually universal and social status and acceptance depend, in large part, on being married and creating a new family An additional problem is that many of these men are rural peasants of low socioeconomic class and with limited education So, in many communities today there are growing numbers of young men in the lower echelons of society who are marginalized because of lack of family prospects and who have little outlet for sexual energy.

A number of commentators predict that this situation will lead to increased levels of antisocial behavior and violence and will ultimately present a threat to the stability and security of society 31 , 45 — There is some empirical evidence to fear such a scenario.

Gender is a well-established individual-level correlate of crime, and especially violent crime It is a consistent finding across cultures that an overwhelming percentage of violent crime is perpetrated by young, unmarried, low-status males 50 — In India, a study carried out between and showed a strong correlation between homicide rates in individual states across the country and the sex ratio in those states, after controlling for potential confounders such as urbanization and poverty The authors concluded that there was a clear link between sex ratio and violence as a whole, not just violence against women as might be assumed when there is a shortage of females.

These analyses were repeated by Hudson and Den Boer 46 , who showed that the relationship between sex ratio and murder rates at the level of the Indian state persisted through the late s. In China, young male migrant workers are thought to be responsible for a disproportionate amount of urban crime, especially violent crime.

There is also evidence that, when single young men congregate, the potential for more organized aggression is likely to increase substantially 45 , Hudson and Den Boer, in their provocative writings on this subject 45 , 46 , go further, predicting that these men are likely to be attracted to military or military-type organizations, with the potential to be a trigger for large-scale domestic and international violence. A number of other consequences of an excess of men have been described, but there is very little evidence for causation.

It is intuitive that if sexual needs are to be met this will lead to a large expansion of the sex industry, including its more unacceptable practices such as coercion and trafficking. The sex industry has expanded in both India and China in the last decade 55 , 56 ; however, there are a number of reasons for this expansion, and the part played by a high sex ratio is impossible to isolate without specific research addressing this question.

Indeed, in China the highest numbers of sex workers are in areas where the sex ratio is least distorted, for example in the border areas of Yunnan Province The recent rise in numbers of sex workers in China has been attributed more to greater mobility, increased socioeconomic inequality, and a relaxation in sexual attitudes, than to an increase in the sex ratio 57 , There is much anecdotal evidence regarding increases in trafficking of women, both for the sex industry and marriage, in both India and China 59 , 60 , although it is impossible to say whether gender imbalance is a contributory factor in this rise.

Reports would suggest that trafficking is more common in parts of Africa and Eastern Europe where the sex ratio is normal It has also been suggested that a shortage of women may lead to a rise in homosexual behavior 31 , not implying that the shortage of women will produce homosexuals, but rather that an increasing tolerance toward homosexuality, together with the surplus of males, may lead to large numbers of covert homosexuals openly expressing their sexuality. The latter could be viewed as a positive outcome, and there are others.

First, access to prenatal sex determination results in an increase in the proportion of wanted births, leading to less discrimination against girl children and lower female mortality.

India, South Korea, China, Pakistan, and Bangladesh have all reported reductions in differential mortality in the last decade 2 , Second, gender imbalance will lead to a reduction in birth rate, which may be particularly beneficial in countries trying to control population growth Third, as the number of women in a society decreases, so their social status should increase and they should benefit from their enhanced value Ultimately, this may lead to more balanced sex ratios because couples will choose to have girls.

However, it has also been argued that the increased value of women could have a negative side, especially in rural society; increased female value may not benefit the woman herself, but rather the males around her. Her father, husband, and in-laws all hold her value, so when her value increases her life is more controlled by them.

Hudson and Den Boer 45 cite as examples the increase in kidnapping and trafficking of women that has been reported from many part of Asia, as well as the recent large increases in dowry prices in parts of India. Governments in affected countries are taking action. Nothing can realistically be done in the short term to reduce the current excess of young males, but much can be done to reduce sex selection now, and this will benefit the next generation.

China has set an ambitious, but almost certainly unachievable, target: to lower the sex ratio to normal by In China and India, laws forbidding infanticide, abandonment, and neglect of female children already exist but need to be strictly enforced.

For trafficking and kidnapping, penalties are harsh people-trafficking is a capital crime in China but detection is difficult.

Sex-selective abortion, however, is carried out by medical personnel in hospitals and clinics, and enforcement of the law banning the practice should be straightforward. Stricter enforcement has been successful in reducing the sex ratio in South Korea, where in eight physicians in Seoul had their licenses suspended for performing sex determination.

In the following year, the sex ratio in Seoul fell from to suggesting that this punitive action had a deterrent effect for other physicians Other countries could learn from this example. Other measures include public awareness campaigns, which should focus on the problems facing young men in finding brides. More importantly, equal social and economic rights for males and females must be guaranteed, for example, in relation to rights of inheritance.

Basic health care should be available free of charge, so that parents are not deterred by financial constraints from seeking health care for their daughters. In addition, special supportive measures should be provided for families with no sons, to ensure protection for parents in old age.