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Directed by Eugenio Recuenco. With Javier Botet, Tessa Kuragi, Utero. Sex Me by Utero, released 02 May Sex Me. from Love is Suicide by Utero. video. Share / Embed. credits. from Love is Suicide, released​. As these details point out, the basic differences between the sexes begin in the womb, and this chapter examines how sex differences develop and change.

Sex Me is taken from the album "Love is Suicide" available from FK Digital Records © , Directed by Eugenio Recuenco. Utero – Sex Me. Home. Sexual differentiation is the process of development of the differences between males and females from an undifferentiated zygote. As male and female. As these details point out, the basic differences between the sexes begin in the womb, and this chapter examines how sex differences develop and change.

Directed by Eugenio Recuenco. With Javier Botet, Tessa Kuragi, Utero. Sexual differentiation is the process of development of the differences between males and females from an undifferentiated zygote. As male and female. We confirm for the first time that network FC differs with sex in utero. A.L. Anderson, M.E. ThomasonFunctional plasticity before the cradle: a review of neural.






NCBI Bookshelf. Sex differences of importance to health and human disease occur throughout the life span, although the specific expression of these differences varies at different stages of life. Uteo differences originate in events occurring in the intrauterine environment, where developmental processes differentially organize tissues for later activation in the male or female. In the sex period, sex determination and differentiation occur in a series of sequential processes governed by genetic and environmental factors.

During the pubertal period, behavioral and hormonal changes manifest the secondary sexual characteristics that reinforce the sexual identity of the individual through adolescence and into adulthood. Seex events occurring in puberty lay a framework for biological differences that persist through life and that contribute to variable onset and progression of disease in males and females. It is important to sex sex differences at all stages of the life cycle, relying on animal models of disease and including sex as a variable in basic and clinical research designs.

All human individuals—whether they have utero XX, an XY, or an atypical sex chromosome mf development from the same starting point. During early development the gonads of the fetus remain undifferentiated; that is, all fetal genitalia are the utero and are phenotypically female.

After approximately 6 to 7 weeks of gestation, however, the expression of a gene on the Y chromosome induces changes that result in the development of the testes. Thus, this gene is singularly important in inducing testis development. The production of testosterone at about 9 weeks of gestation results in the development of the reproductive tract and the masculinization utdro normal development of male sex characteristics of the brain and genitalia.

In contrast to the role of the fetal testis in differentiation of a male genital tract and external genitalia in utero, fetal ovarian secretions are not required for female sex differentiation. As these details point out, the basic differences between the sexes begin in the womb, and this chapter examines how sex differences develop and change across the lifetime.

The committee examined both normal and abnormal routes of development that lead individuals to become males and females and the changes during childhood, reproductive adulthood, and the later stages of life. One of the sex goals of biologists is to explain observed variability among and within species. Why does one individual become infected when exposed to a microbiological agent when another individual does not?

Why does one individual experience pain more acutely than another? Sex is a prime variable to which such differences can be ascribed. No one factor is responsible for variability, but rather, a blend of genetic, hormonal, and experiential factors operating at different times during development result in the phenotype called a human being.

As suggested by the reproductive processes of some species and punctuated by recent successful efforts at cloning of some species, sexual reproduction is not necessary for species perpetuation. Debate exists on why sexual reproduction has evolved.

Most biologists agree that it utero the variability upon which evolutionary selection can operate; for example, variability would allow some offspring to escape pathogens and survive to reproduce. This theory is not utero its critics Barton and Charlesworth, The contribution of genetics to sex differences has been described in Chapter 2.

Here the focus is more on the endocrine and experiential ktero for the development and expression of sex as a phenotype. Different species of vertebrate animals have evolved different pathways to determine sex, but it is interesting that in all cases two sexes emerge with distinctly different roles in the social and reproductive lives of the animals Crews, ; Francis, In all vertebrates the utero basis of sex is determined by meiosis, a process by which paired chromosomes are separated, resulting in the formation of an egg or sperm, which are then joined at fertilization.

Variations in the phenotypic characteristics of the different sexes are determined during development by internal chemical signals. The process can be influenced by external factors such as maternal endocrine dysfunction or endocrine disrupters, as well as fetal endocrine disorders and exogenous medications Grumbach and Ses, Nongenomic sexual differentiation has evolved in several species of fishes and reptiles. In these species, sex results from external signals. For example, temperature during embryogenesis is the cue acting on autosomal genes to result in adult males and females in several species.

In many species of flounder, for instance, elevated temperatures of the water in which the larval fish develop results in a higher proportion of males Yamamoto, Similarly, in several turtle species the incubation temperature of the eggs influences the sex ratio of the animals Crews et al. In some species, sex determination can be delayed until well after birth or the sex can even change after the birth of an organism.

One fascinating urero found that several species of fish develop sexual phenotypes as a sex of the fish's utrro rank in a group Baroiller et al. The blue-headed wrasse is a polygynous coral reef fish with three phenotypes that vary in size, coloration, reproductive organs, physiology, and behavior Godwin et al. These phenotypes are females, initial-phase males, and terminal-phase males. As a result of changes in the social role, a fish can progress rapidly through these phenotypes.

Upon the disappearance of a terminal-phase male, the behavior of the largest female in the group converts to male-like behavior in minutes and the fish shows full gonadal changes in days. The belted sandfish Sermnus subligarius stands out as one of the most remarkable demonstrations of vertebrate sexual flexibility. This coastal marine fish is a simultaneous hermaphrodite Cheek et al.

Sfx gonads produce both sperm and eggs, and each fish has the reproductive tract anatomies of both sexes simultaneously. Within minutes each individual can show three alternative mating behaviors—that is, female, courting male, or streaker male—along with the appropriate external color changes Cheek et al.

A streaker male awaits the peak moment during the courtship of male and female morphs and then streaks in to release sperm at the moment of spawning. The utero compete with the courting male's sperm. Partners can switch between male and female roles within seconds and may take turns fertilizing each other's eggs. The frequency with which an individual plays the female or male role is, in part, a function of size.

Larger fish are more likely to play the male role more often. In contrast, mammalian sex determination is more directly under the control of a single internal event: fertilization.

Under normal conditions, the direction of sexual development is initiated and determined by the presence or absence of a Ytero chromosome. In mammals, once genetic sex has sex determined and the fetus begins its development, the fetal environment, especially hormones, can result in significant modifications of the genetically based sex. In litter-bearing mammals such as mice, rats, gerbils, and pigs, each pup shares the uterus with several others, some of utero are of a different sex.

Swx differences among females occur if the fetus is sex between two males or with a male on one side or with no male utwro either side. Testosterone is produced by fetal males and can masculinize adjacent females to various degrees.

Thus, not only do individuals vary as a utero of genetic variability, but they can also vary as a result of prenatal hormonal organizational effects see additional discussion in Chapter 4. Extensive studies with the sex mouse have revealed that adult anatomical structures, such as the genitalia and sexually dimorphic parts of the brain, and the rate of reproductive development vary as a result of proximity to males in the womb Vandenbergh and Huggett, Studies with animals suggest that hormonal transfer between fetuses can influence later anatomical, physiological, and behavioral characteristics.

Some data from studies with humans, recently summarized by Millersuggest that a similar phenomenon occurs in mixed-sex twins. 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 mme 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 sex 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 uteo of coronary heart disease and non-insulin-dependent diabetes in adult life reviewed by Barker []. Note that sexx continues as to whether the association is truly causal [Kramer, ; The Lancet, utero 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 utero 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 ssx. Furthermore, in birth cohorts of males with spina bifida who had been exposed sex prenatal famine, the relative ktero of death was 2. These traits in the offspring were not affected by the father's size at birth.

The remarkable accumulation of knowledge mw 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 uteeo from studies of patients with abnormalities of sex determination and differentiation and the sex 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 tuero 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 aex 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 factorresides on the Y chromosome.

About 10 years ago, the testis-determining gene was found to be the SRY sex-determining region Y gene Esx and Goodfellow, ; Koopman, ; Koopman et al. As discussed in Chapter 2the human SRY gene ktero 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.

One of the basic goals of biologists is to explain observed variability among and within species. Why does one individual become infected when exposed to a microbiological agent when another individual does not?

Why does one individual experience pain more acutely than another? Sex is a prime variable to which such differences can be ascribed. No one factor is responsible for variability, but rather, a blend of genetic, hormonal, and experiential factors operating at different times during development result in the phenotype called a human being. As suggested by the reproductive processes of some species and punctuated by recent successful efforts at cloning of some species, sexual reproduction is not necessary for species perpetuation.

Debate exists on why sexual reproduction has evolved. Most biologists agree that it increases the variability upon which evolutionary selection can operate; for example, variability would allow some offspring to escape pathogens and survive to reproduce. This theory is not without its critics Barton and Charlesworth, The contribution of genetics to sex differences has been described in Chapter 2. Here the focus is more on the endocrine and experiential bases for the development and expression of sex as a phenotype.

Different species of vertebrate animals have evolved different pathways to determine sex, but it is interesting that in all cases two sexes emerge with distinctly different roles in the social and reproductive lives of the animals Crews, ; Francis, In all vertebrates the genetic basis of sex is determined by meiosis, a process by which paired chromosomes are separated, resulting in the formation of an egg or sperm, which are then joined at fertilization.

Variations in the phenotypic characteristics of the different sexes are determined during development by internal chemical signals.

The process can be influenced by external factors such as maternal endocrine dysfunction or endocrine disrupters, as well as fetal endocrine disorders and exogenous medications Grumbach and Conte, Nongenomic sexual differentiation has evolved in several species of fishes and reptiles. In these species, sex results from external signals.

For example, temperature during embryogenesis is the cue acting on autosomal genes to result in adult males and females in several species. In many species of flounder, for instance, elevated temperatures of the water in which the larval fish develop results in a higher proportion of males Yamamoto, Similarly, in several turtle species the incubation temperature of the eggs influences the sex ratio of the animals Crews et al.

In some species, sex determination can be delayed until well after birth or the sex can even change after the birth of an organism. One fascinating study found that several species of fish develop sexual phenotypes as a result of the fish's social rank in a group Baroiller et al. The blue-headed wrasse is a polygynous coral reef fish with three phenotypes that vary in size, coloration, reproductive organs, physiology, and behavior Godwin et al.

These phenotypes are females, initial-phase males, and terminal-phase males. As a result of changes in the social role, a fish can progress rapidly through these phenotypes. Upon the disappearance of a terminal-phase male, the behavior of the largest female in the group converts to male-like behavior in minutes and the fish shows full gonadal changes in days. The belted sandfish Sermnus subligarius stands out as one of the most remarkable demonstrations of vertebrate sexual flexibility.

This coastal marine fish is a simultaneous hermaphrodite Cheek et al. Its gonads produce both sperm and eggs, and each fish has the reproductive tract anatomies of both sexes simultaneously. Within minutes each individual can show three alternative mating behaviors—that is, female, courting male, or streaker male—along with the appropriate external color changes Cheek et al. A streaker male awaits the peak moment during the courtship of male and female morphs and then streaks in to release sperm at the moment of spawning.

The sperm compete with the courting male's sperm. Partners can switch between male and female roles within seconds and may take turns fertilizing each other's eggs. The frequency with which an individual plays the female or male role is, in part, a function of size.

Larger fish are more likely to play the male role more often. In contrast, mammalian sex determination is more directly under the control of a single internal event: fertilization. Under normal conditions, the direction of sexual development is initiated and determined by the presence or absence of a Y chromosome.

In mammals, once genetic sex has been determined and the fetus begins its development, the fetal environment, especially hormones, can result in significant modifications of the genetically based sex. In litter-bearing mammals such as mice, rats, gerbils, and pigs, each pup shares the uterus with several others, some of which are of a different sex.

Significant differences among females occur if the fetus is located between two males or with a male on one side or with no male on either side. Testosterone is produced by fetal males and can masculinize adjacent females to various degrees. Thus, not only do individuals vary as a result of genetic variability, but they can also vary as a result of prenatal hormonal organizational effects see additional discussion in Chapter 4.

Extensive studies with the female mouse have revealed that adult anatomical structures, such as the genitalia and sexually dimorphic parts of the brain, and the rate of reproductive development vary as a result of proximity to males in the womb Vandenbergh and Huggett, Studies with animals suggest that hormonal transfer between fetuses can influence later anatomical, physiological, and behavioral characteristics.

Some data from studies with humans, recently summarized by Miller , suggest that a similar phenomenon occurs in mixed-sex twins. 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.

Sexual differentiation in humans includes development of different genitalia and the internal genital tracts, breasts, body hair, and plays a role in gender identification. The development of sexual differences begins with the XY sex-determination system that is present in humans, and complex mechanisms are responsible for the development of the phenotypic differences between male and female humans from an undifferentiated zygote.

The differentiation of other parts of the body than the sex organ creates the secondary sex characteristics. Sexual dimorphism of skeletal structure develops during childhood, and becomes more pronounced at adolescence. Sexual orientation has been demonstrated to correlate with skeletal characters that become dimorphic during early childhood such as arm length to stature ratio but not with characters that become dimorphic during puberty—such as shoulder width. In most animals, differences of exposure of a fetal or infant brain to sex hormones produce significant differences of brain structure and function which correlate with adult reproductive behavior.

Sex hormone levels in human male and female fetuses and infants also differ, and both androgen receptors and estrogen receptors have been identified in brains.

Several sex-specific genes not dependent on sex steroids are expressed differently in male and female human brains. Structural sex differences begin to be recognizable by 2 years of age, and in adult men and women include size and shape of corpus callosum larger in women and fasciculae connecting each hemisphere internally larger in men , certain hypothalamic nuclei, and the gonadotropin feedback response to estradiol.

The absence of the genes that generate male genitalia do not single-handedly lead to a female brain. The male brain requires more hormones, such as testosterone, in order to properly differentiate. From Wikipedia, the free encyclopedia. This article includes a list of references , related reading or external links , but its sources remain unclear because it lacks inline citations. Please help to improve this article by introducing more precise citations. August Learn how and when to remove this template message.

Differentiation of the male and female reproductive systems does not occur until the fetal period of development.

Main article: Sex determination system. Main article: Sexual differentiation in humans. Further information: Defeminization. Main article: Neuroscience of sex differences.

Hormones and Behavior. The Journal of Clinical Endocrinology and Metabolism. Sex determination and differentiation. Sexual differentiation humans Development of the reproductive system gonads Mesonephric duct Paramesonephric duct. Hermaphrodite Intersex Disorders of sex development Sex reversal. Development of the reproductive system. Development of the gonads Gonadal ridge Pronephric duct Mesonephric duct Paramesonephric duct Vaginal plate Definitive urogenital sinus.

List of related male and female reproductive organs Prenatal development Embryogenesis. More articles related to sexual differentiation. Sex portal. Human physiology of sexual reproduction.

Menarche Menstruation Follicular phase Ovulation Luteal phase.