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Reproduction. Introduction sexual determination, differentiation and development Hormones and male reproduction Hormones and female reproduction Hormones of pregnancy, parturition and lactation. Parents with diploid somatic cells. Male. Female. Meiotic division of germ cells.
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Reproduction • Introduction • sexual determination, differentiation and development • Hormones and male reproduction • Hormones and female reproduction • Hormones of pregnancy, parturition and lactation
Parents with diploid somatic cells Male Female Meiotic division of germ cells Meiotic division of germ cells Haploid ovum Haploid sperm Fertilization Diploid zygote Mitosis Offspring with diploid somatic cells Fig. 16-1, p.707
Sexual determination, differentiation and development • Sex determination • Genetic sex • established at the time of conception • governs the development of gonadal sex • two most common chromosomal sex-determining systems: • Mammalian sex determination means testis determination—TDF (SRY)
Sex DeterminationChromosomal Sex Determination • XO/XX systems • (Grasshoppers) • XX/XY systems • (Some Plants, Insects, Reptiles, all Mammals) • ZZ/ZW systems • (Birds, Moths, Some Amphibians and Fish)
Simple molecular pathway for sex determination in the mammalian gonads Nature Medicine 14, 1197 - 1213 (2008)
Independent origins of sex chromosomes in birds, snakes, and mammals. Vallender E J , Lahn B T PNAS 2006;103:18031-18032 ©2006 by National Academy of Sciences
Sexual determination, differentiation and development • Sexual differentiation • begins with the establishment of chromosomal sex at fertilization, followed by the development of gonadal sex and culminating in the formation of sexual phenotypes • Differentiation of Gonads • differentiation of testis requires TDF • Differentiation of accessory sex organs and external genitalia • mullerian-inhibiting hormone • testosterone
Sexual determination, differentiation and development • Differentiation of the brain • male vs female • preoptic area • gonadotropins secretion pattern • sexual behavior • induced by testosterone • female patterns are predetermined and male patterns are induced by androgen during critical period
Sexual determination, differentiation and development • Puberty • acquisition of reproductive capability and is manifested by appearance of secondary sexual characteristics • hormones of the brain-pituitary-gonadal axis • appearance of secondary sexual characteristics • rapid body growth • Hormonal control of puberty • Brain is likely the site of activation during puberty • pulsatile GnRH secretion • sensitivity to negative feedback of gonadal steroids • melatonin may control the timing of puberty
Male reproduction • Contains seminiferous tubules • 3 major types of cells: germ cells, Sertoli cells and Leydig cells • Leydig cells: produce androgens • Sertoli cells: support germ cells development and differentiation
Male reproduction • Androgen production • mainly produced in Leydig cells • cholesterol serves as the substrate • main androgen is testosterone • function of androgens: act in one of 3 forms, DHT, T and E2 • sex determination and differentiation • male reproductive organs and secondary sexual characteristics • spermatogenesis • feedback on gonadotropin
Male Reproduction • Spermatogenesis • differentiation of spermatogonia to spermatozoa • involves three steps • proliferation of spermatogonia • meiosis of spermatocytes to form spermatids • differentiation of spermatids to form spermatozoa (spermiogenesis): morphological remodeling
Stages Spermatogonium Spermatogonia Mitotic Proliferation 2n (diploid number; doubled strands) Primary Spermatocytes Meiosis Second meiotic division Spermatids Packaging Chromosomes in each cell 2n (diploid number; single strands) One daughter cell remains at the outer edge of the seminiferous tubule to maintain the germ cell line One daughter cell moves toward the lumen to produce Spermatozoa 2n (diploid number; single strands) First meiotic division Secondary Spermatocytes n (haploid number; single strands) n (haploid number; doubled strands) Spermatozoa n (haploid number; single strands) Fig. 16-9, p.721
+ + Anterior pituitary LH-secreting cells FSH-secreting cells FSH LH + + Testes Sertoli cell Leydig cell Spermatogenesis Hypothalamus Gonadotropin-releasing hormone — — Inhibin Testosterone Fig. 16-11, p.723
Male reproduction • Regulation of steroidogenesis • FSH is a major regulator, especially in the initiation of spermatogenesis • increases the size of testis • stimulates the replication of spermatogonia • increases LH-R #, contribute to T production • Testosterone is essential for maintenance of spermatogenesis • Activin: replication of spermatogonia • Inhibin: inhibits differentiation of spermatogonia
Male reproduction • Regulation of androgen production • LH: major regulator • Increases cholesterol transport into inner mitochondrial membrane • increases enzyme activity (SCC, 3b-HSD) • FSH: enhance LH-R#, protentiates LH effect • Activin: increases basal T but inhibits LH-induced T production, inhibin blocks activin effects
Female reproduction • Anatomy of female reproductive system (human)
Stages Chromosomes in each cell Oogonium 2n (diploid number; double strands) (arrested in first meiotic division) Primary oocytes Secondary oocyte First polar body Second polar body Mature ovum 2n (diploid number; single strands) Mitotic proliferation prior to birth 2n (diploid number; doubled strands) Enlarged primary oocyte (first meiotic division completed just prior to ovulation) n diploid number; doubled strands) Meiosis (second meiotic division completed after fertilization) n (haploid number; single strands) from ovum plus n (haploid number; single strands) from sperm for diploid fertilized ovum with 2n chromosomes Polar bodies degenerate Fig. 16-15, p.733
Female reproduction • Ovary • produces hormones • produces eggs • functional units: ovarian follicles • fallopain tubes • transport of eggs • fertilization occurs here • uterus • site for fetal development
Female reproduction • Ovary contains follicles at different stages of development
Female reproduction • Functions of ovary • folliculogenesis
Female reproduction • Ovarian hormonogenesis • Steroids: estradiol and progesterone
Female reproduction • Estradiol: • synthesized mainly by granulosa cells • stimulated by FSH and LH • act on CNS to maintain libido and sexual behavior • feedback regulation of GnRH, LH and FSH (+ve or -ve) • function of female reproductive organs • oocyte maturation • parturition and lactation • metabolic functions • anabolic: weight gain • bone mineral deposition
Female reproduction • Progesterone • synthesized mainly by corpus luteum • stimulated by LH (primed by FSH) • act on CNS to increase sexual receptivity • feedback regulation of GnRH, LH and FSH (-ve) • effects on reproductive tract • pregnancy • metabolic functions • increases basal metabolic rate and thus thermogenic action
Female reproduction • Others • ovary also produces many nonsteroidal hormones • inhibin and activin • regulate FSH secretion and ovarian function • prostaglandins • PGF2a induces CL regression • PGF2a and PGE2 required for ovulation • insulin-like growth factor • stimulates granulosa cell proliferation; inhibits apoptosis; induces steroidogenesis; induces maturation
Female reproduction • Reproductive cycle • cyclic change of reproductive activity • seasonal reproductive cycle • related to environmental changes, e.g. photoperiod, temperature, food availability, etc. • estrous cycle (menstrual cycle in primates) • visible sign of ovulation • a behavior strategy to ensure that the female is mated at the time of ovulation
Female reproduction • human menstrual cycle • cycle of ovarian activity that repeat at approximately one-month interval (menstru=monthly) • menstruation is used to indicate the periodic shedding of endometrium, which become thickened prior to menstruation under stimulation by ovarian steroids • shedding of endometrium is accompanied by bleeding
Female reproductive physiology • Ovarian events during menstrual cycle
Female reproduction • Regulation of ovarian functions • Follicular phase: • FSH level is elevated at the beginning of the cycles • FSH stimulates follicular development and production of E2 and inhibin • E2 and inhibin feedback to inhibit FSH and thus FSH level decreases • the follicle that has the highest sensitivity to FSH will be selected and develops into a mature follicle • growth of mature follicle is accompanied by rapid increase in E2 • E2 triggers LH surge (positive feedback)
Female reproduction • ovulation: rupture of follicular wall and release of oocyte • triggered by LH surge • other hormones: prostaglandin: histamine • Luteal phase • CL formed • progesterone produced by CL • together with E2 feedback to suppress FSH and LH : prevent new follicular development • if pregnancy occurs, hCG stimulates progesterone production and CL function maintained • if no implantation, CL regresses and progesterone level declines (about day 22)
Female reproductive physiology • Regulation of uterine events during menstrual cycle • menstrual phase • starts at the first day of bleeding (last 3-5 days) • endometrium degenerates • resulted from decrease in progesterone • proliferative phase • between the cessation of menstruation and ovulation (about 10 days) • endometrium regenerates and thickens • estradiol induces endometrium and myometrium growth, as well as progesterone receptors
Female reproduction • secretory phase • between ovulation and the onset of next menstruation • occurs when the ovary is at luteal phase • under the action of progesterone and estradiol, endometrium is prepared to accept and nourish an embryo • thick, vascular and “spongy” in appearance • accumulation of glycogen and various enzymes • Progesterone also inhibits myometrium activity