Sex Determination and Development of Reproductive Organs

Sex Determination and Development of Reproductive Organs Sex determination The SRY + gene is necessary and probably sufficient for testis development The earliest sexual difference appears in the gonad Genital duct development External genitalia development Synthesis of mammalian sex hormones Hormonal control of fetal sexual development Hormonal control of postnatal sexual development

Sexual dimorphism In many species, adult males and females differ not only in their reproductive organs but also in secondary sex characteristics, such as size, weaponry, and ornaments. In deer, males are considerably larger and seasonally produce large antlers, which they use for fighting.

A male is an individual with testes. A female is an individual with ovaries. A true hermaphrodite is an individual with both testicular and ovarian tissues. Sex Determination is the natural event by which an organism is set to become either a male or a female.

Sex Determination in mammals depends on Y Chromosome In the presence of a Y chromosome, a male develops. In the absence of a Y chromosome, a female develops.

Genotypic sex determination in mammals. Males have two sexually dimorphic chromosomes, designated X and Y, while females have two X chromosomes. A stands for one complete set of non-sex chromosomes, or autosomes. Thus, males produce two types of sperm, designated AX and AY. This system generates a sex ratio (proportion of male offspring ) of 0.5, as long as XA and YA sperm fertilize equally well, and provided that AAXX and AAXY embryos are equally viable.

Primary sex differentiation in the human embryo All diagrams show transverse sections. (a) Indifferent gonad during 6th week of gestation. (b) Ovary during 7th week. Cortical (outer) portions of primitive sex cords form follicles. (c) Testis during 8th week. Medullary (inner) portions of primitive sex cords form testis cords.

After the indifferent stage, the activity of Sry +, a Y-linked gene, is critical: It controls the production, in the developing testis, the differentiation of cells producing two key hormones: testosterone and anti-műllerian hormone

Seminiferous tubules in mammalian testis (a) schematic drawing of testis (b) photograph showing tubules in cross section (c) drawing of segment outlined in part (b)

Indifferent stage of human sexual development shown in transverse section. The immigrating primordial germ cells are surrounded by proliferating gonadal epithelial cells to form primitive sex cords. The mesonephric (Wolffian) and paramesonephric (Müllerian) ducts are both in place. The former functions at this stage as part of the embryonic kidney.

Genital duct development in the human female (a) Fourth month of gestation. Both Müllerian and Wolffian ducts are in place. (b) At birth, the proximal portion of each Müllerian duct has formed an oviduct. The distal portions of both Müllerian ducts have fused to form uterus and upper vagina. The Wolffian duct has degenerated.

Genital duct development in the human male (a) Fourth month of gestation. The proximal portion of the Wolffian duct is embedded in the embryonic kidney. (b) After descent of the testis, the mesonephric tubules have become efferent tubules. The Wolffian duct has formed epididymis, ductus deferens, and seminal vesicle. The Müllerian duct has almost completely degenerated.

Development of the external genitalia in the human The genital tubercle forms either the corpora cavernosa of the penis or all of the clitoris. The urogenital groove becomes either the urethra or the vestibule of the vagina. The urethral folds form either the corpus spongiosum of the penis or the labia minora. The genital swellings give rise to either the scrotum or the labia majora.

Synthetic pathways for vertebrate sex steroid hormones Testosterone is synthesized via progesterone from cholesterol. In the presence of the enzyme aromatase, testosterone is converted into estrogen. In the presence of 5αreductase, testosterone is converted to 5αdihydrotestosterone.

Gene Activation by Steroid Hormones Steroid hormones (including progesterone and testosterone) have receptor proteins. The hormone binds to the receptor while displacing an inhibitory protein. Two hormonereceptor complexes typically form a dimer that binds to specific DNA sequences (steroid response elements). In concert with other transcription factors, the bound dimer controls the transcription of several target genes.

Somatic sexual development in mammals. Primary (gonadal) sex differentiation depends on the Sry + gene, whereas secondary sex differentiation is controlled by sex hormones produced in the gonads.

Genetic Disorders Interfering with Secondary Sex Differentiation Congenital adrenal hyperplasia (CAH) based on loss-of-function alleles for enzymes converting progesterone to metabolic steroids. Leads to elevated testosterone and masculinisation in females. Androgen insensitivity loss of function in X- linked gene for androgen receptor. Allows development of female external genitalia and secondary sex characteristics in males with normal SRY + and (non-descended) testes. Guevedoces (penis at 12 years of age) - based on autosomal recessive alleles for 5-α-reductase, which metabolizes testosterone to DHT. Affects only males.

How Male and Female Brains Become Different Sex differences in brain development and activity Distribution of sex hormone receptors in the brain Seasonal hormone levels control bird singing Perinatal exposure to sex hormones affects adult reproductive behavior and brain anatomy The organizational hypothesis Congenital adrenal hyperplasia Progestin-induced pseudohermaphroditism Gender has biological underpinnings

Sex hormone receptors have distinct distributions in the brain. Photographs show frontal sections of lizard brains hybridized in situ with probes for mrnas encoding specific hormone receptors. Androgen receptor mrna (top) accumulates in brain areas involved in aggression and copulation, such as AME and NSL. Progesterone receptor mrna (bottom) accumulates in areas involved in ovulation and sexual receptivity. Other brain areas (including MPA) show mrnas for both receptors.

Hormones Cause Sex-Specific Brain Activity The receptors for androgens (AR), estrogen (ER), and progesterone (PR) have distinct distributions, which are alike in men and women. Nevertheless, the prevalence of different hormones leads to sex-specific brain activity patterns.

Sexually dimorphic nucleus of the preoptic area (SDN-POA) in the rat hypothalamus The SDN-POA is located on both sides of the third ventricle (V) of the rat brain and is larger in normal males (a) than in normal females (b). Perinatal treatment of rats with either testosterone (c) or its estrogen metabolite (d) enlarges (masculinizes) the SDN-POA. (a) (b) (c) (d)

Third interstitial nucleus of the anterior hypothalamus (INAH3) in the human

Congenital Adrenal Hyperplasia or Progestin-Induced Pseudohermaphroditism Female infants with this genetic or maternal medicationinduced disorder show enlargement of the clitoris and fused urogenital folds.

From E.O. Wilson (1975)

Five male archers advance in single file, led by a man in a head dress. They seem confident, almost cocky. Archers are typically found in cave paintings of Cro-Magnons dating 12-4 kya.

Cro-Magnon woman strolling with a child whose hair is pulled up in twin puffs. The hand-holding and the woman s attentive posture suggest the child is her daughter, and that children were raised primarily by their mothers.

How Male and Female Brains Become Different Sex differences in brain development and activity Distribution of sex hormone receptors in the brain Seasonal hormone levels control bird singing Prenatal exposure to sex hormones affects adult reproductive behavior and brain anatomy The organizational hypothesis Congenital adrenal hyperplasia Progestin-induced pseudohermaphroditism Gender has biological underpinnings