NOTES NOTES SEXUAL DEVELOPMENT DEVELOPMENT OF THE REPRODUCTIVE SYSTEM osms.it/reproductive-system-dev SEXUAL DIFFERENTIATION ▪ Series of events begins at conception, ends with sexual characteristics acquisition (designated biologically male/female) ▪ During ﬁrst ﬁve gestational weeks ▫ Gonadal ridge develops, later becomes differentiated gonads ▪ Week 6 ▫ Primordial germ cells start migrating from yolk sac towards gonadal ridge ▪ Week 7 ▫ Primordial germ cells promote gene expression contained in sex chromosomes ▪ Wolfﬁan, Müllerian ducts: structures that will develop into rest of reproductive tract; remain undifferentiated until week 8 MALE DEVELOPMENT Male gonadal development ▪ Embryo genetically male → gene expression in Sex-determining Region in Y chromosome (SRY) promoted ▫ SRY-region genes promote testisdetermining factor production → testis-determining factor acts on undifferentiated gonads → gonadal transformation into testes ▫ Gonadal ridge becomes seminiferous tubules, rete testis, straight tubules ▪ Testes contain three functional cell types ▫ Germ cells: produce spermatogonia → produce male gametes in puberty ▫ Sertoli cells: synthesize anti-Müllerian hormone ▫ Leydig cells: synthesize testosterone Figure 66.1 Illustration of the migration of primordial germ cells to the gonadal ridge in week 6. At this point, the gonad is undifferentiated, meaning that it can develop into ovaries or testes. OSMOSIS.ORG 581
Male internal reproductive organ development ▪ Wolfﬁan ducts give rise to male internal genitalia ▫ AKA mesonephric duct/mesonephros ▫ Meso = middle, in between; nephros = kidney ▫ Two functions: connects primitive kidney to cloaca; develops into male genitalia ▫ Growth, differentiation stimulated by testosterone ▪ Male internal reproductive organ development depends on Sertoli cells, Leydig cells, urogenital sinus ▪ Sertoli cells: synthesize, secrete antiMüllerian hormone; AKA Müllerian inhibiting substance ▫ Promotes Müllerian/paramesonephricduct atrophy ▪ Leydig cells: synthesize, secrete testosterone → become internal male genitalia ▫ Promotes Wolfﬁan/mesonephric-duct growth, differentiation ▪ Urogenital sinus: develops into external reproductive organs; undifferentiated until gestational week 9 ▫ Urethral folds → urethra (both) ▫ Labioscrotal swellings → scrotum ▫ Primordial phallus → penis Male external reproductive organ development ▪ Male external genitalia differentiation from urogenital sinus depends on testosterone presence ▫ 5 alpha reductase in target tissues converts testosterone → more potent dihydrotestosterone ▫ Dihydrotestosterone: responsible for masculinizing external genitalia Figure 66.2 Biologically male sexual differentiation, week 7: genes in Sex-determining Region of Y chromosome (SRY) code for testis-determining factor (which initiates development of testes). Primitive sex cords → medullary cords that carry primitive germ cells deeper into mesoderm. The surface epithelial layer of each gonad thins out → tunica albuginea. Later, medullary cords → seminiferous tubules, straight tubules, rete testis. The primordial germ cells settle in seminiferous tubules mature into dormant spermatogonia. During puberty, spermatogonia start dividing → sperm (male gametes). During week 8, some cells in the seminiferous tubule walls differentiate into Sertoli cells, and cells between the seminiferous tubules differentiate into Leydig cells. 582 OSMOSIS.ORG
Chapter 66 Reproductive Physiology: Sexual Development FEMALE DEVELOPMENT Female gonadal development ▪ Without functional SRY gene ▫ Week 9: ovaries begin developing ▫ Week 10: ovarian cortex, inner medulla distinguishable ▪ Ovaries contain three functional cell types ▫ Germ cells: produce oogonia; located in ovarian cortex (oogonia—haploid cells that remain arrested in prophase 1 of meiosis until ovulation) ▫ Granulosa cells: synthesize estradiol ▫ Theca cells: synthesize progesterone ▪ Ovarian follicle: oogonium surrounded by granulosa cells, connective tissue Female internal reproductive organ development ▪ Müllerian duct → female genitalia ▫ AKA paramesonephric duct/ paramesonephros ▫ Para = on the side of; meso = middle, in between; nephros = kidney ▪ Female internal reproductive organ development primarily depends on testes absence ▫ Lack of testosterone induces Wolfﬁan duct degeneration ▫ Lack of anti-Müllerian hormone promotes Müllerian ducts persistence → develop into fallopian tubes, uterus, upper ⅓ of vaginal canal ▫ Rest of female reproductive organs arise from urogenital sinus Female external reproductive organ development ▪ Urogenital sinus develops into external reproductive organs; undifferentiated until gestational week 9 ▫ Urethral folds → urethra (both ⚥), labia minora ▫ Labioscrotal swellings → labia majora, mons pubis ▫ Primordial phallus → clitoris ▪ Female external genitalia differentiation ▫ Androgen absence-dependent (testosterone, dihydrotestosterone) ▪ Phenotypic differentiation complete at week 12 → earliest ultrasound-based sexdetermination date Figure 66.3 Biologically-female sexual differentiation. Since there is no Y chromosome to secrete Testis-determining factor, the undifferentiated gonads develop into ovaries. The rest of the reproductive tract acquires female characteristics in the absence of testosterone. OSMOSIS.ORG 583
Figure 66.4 The genital ducts are initially undifferentiated, tubular structures that run down the embryo’s back inside the two nephrogenic cords on either side of the embryo. The Wolfﬁan and Müllerian ducts start in the thoracic and upper lumbar region and continue down the embryo’s back until they open into the part of the cloaca called the urogenital sinus. Figure 66.5 Male internal reproductive organ differentiation and descent of gonads. Figure 66.6 Female internal reproductive organ differentiation and descent of gonads. 584 OSMOSIS.ORG
Chapter 66 Reproductive Physiology: Sexual Development SEX VS. GENDER ▪ Gender ▫ Socially-constructed characteristics/ behaviors associated with biologically male/female people ▫ E.g. norms, roles, relationships between individuals ▪ Genetic sex ▫ Individual’s chromosomal composition ▫ XY: males ▫ XX: females ▫ Established by oocyte, sperm cell fusion ▪ Gonadal sex ▫ Individual’s reproductive organs ▫ Male: testes ▫ Female: ovaries ▪ Phenotypic sex Internal, external reproductive organ structure ▪ Male genitalia ▫ Internal: prostate, seminal vesicles, vas deferens, epididymis ▫ External: penis, scrotum ▪ Female genitalia ▫ Internal: fallopian tubes, uterus, upper ⅓ vaginal canal ▫ External: clitoris, labia majora, labia minora, lower ⅔ vaginal canal Figure 66.7 Male and female external sex organs. Phenotypical differentiation is complete at week 12. OSMOSIS.ORG 585
PUBERTY & TANNER STAGING osms.it/puberty-tanner-staging PUBERTY ▪ Sexual maturation process involving endocrine, physical changes; controlled by hypothalamic-pituitary-gonadal axis ▪ Begins between ages 10–14 in females; between age 12–16 in males GnRH secretion ▪ Pulses from hypothalamus regulate luteinizing hormone (LH), folliclestimulating hormone (FSH) secretion from anterior pituitary → development of sexual characteristics ▫ Primary sex characteristics: genitals (organs directly involved in sexual reproduction) ▫ Secondary sex characteristics: sex-speciﬁc physical characteristic not necessary involved in sexual reproduction (e.g. pubic hair—both sexes, voice changes—males, breast development—females) Gamete production ▪ Oocytes (females); sperm (males) ▪ Males: LH acts on Leydig cells → produces testosterone; FSH acts on Sertoli cells → produces sperm ▪ Females: LH acts on ovarian follicles → produces progesterone, androstenedione (converted into estrogen) ▫ Estrogen, progesterone levels vary according to menstrual cycle phases Gonadal steroid production ▪ Testosterone (males), estradiol (females) secretion → ↑ circulating sex hormones ▪ Secondary sexual characteristics develop ▪ Stimulate bone growth, ossiﬁcation ▪ Involved in growth hormone production → growth spurt EVENTS OF PUBERTY Gonadarche ▪ Gonadal activation by FSH, LH 586 OSMOSIS.ORG Adrenarche ▪ ↑ adrenal androgen production by adrenal cortex Thelarche ▪ Breast tissue appears ▫ Ovarian estradiol-guided Menarche ▪ First menstruation occurs ▫ Ovarian estradiol-guided ▫ First menstrual cycles tend to be anovulatory Spermarche ▪ First sperm production occurs ▫ FSH, LH, testosterone-guided ▫ Nocturnal sperm emissions, sperm appears in urine Pubarche ▪ Pubic hair appears ▫ Adrenal androgens-guided ▫ Association: body hair; acne; apocrine sweat glands activation Figure 66.8 Puberty begins when pulse generator in hyothalamus begins secreting GnRH in pulses → pulsatile secretion of FSH and LH. In puberty, GnRH receptors in anterior pituitary become more sensitive to GnRH stimulation: small ↑ GnRH = large ↑ FSH, LH levels.
Chapter 66 Reproductive Physiology: Sexual Development TANNER STAGING ▪ System for describing predictable steps during sexual maturation ▪ Centers on two, independent criteria ▫ Appearance: pubic hair in males, females ▫ Genital development: ↑ testicular volume, penile growth (males); breast development (females) FIVE CATEGORIES OF TANNER STAGING Stage 1: pre-pubertal ▪ ⚥ No pubic hair present in either sex ▪ ♂ Small penis, testes ▪ ♀ Have ﬂat-chest Stage 3 ▪ ⚥ Pubic hair becomes coarser ▪ ♂ Penis begins to enlarge in size, length ▪ ♀ Breast mounds form Stage 4 ▪ ⚥ Pubic hair begins to cover pubic area ▪ ♂ Penis begins to widen ▪ ♀ Breast enlargement forms “mound-onmound” breast contour Stage 5: adult ▪ ⚥ Pubic hair extends to inner thigh ▪ ♂ Penis, testes enlarged to adult size ▪ ♀ Breast takes on adult contour Stage 2 ▪ ⚥ Soft pubic hair appears ▪ ♂ Measurable testes enlargement ▪ ♀ Breast buds appear Figure 66.9 Illustration of the ﬁve stages of the Tanner scale in males and females. OSMOSIS.ORG 587