Primary follicles

• FSH stimulates granulosa cell growth

Develop into secondary follicles.

• Appearance of vesicles containing fluid

graafian follicle

• Fusion of its vesicles to form the antrum
• first meiotic division completed (2^o oocyte)
• FSH stimulation--> granulosa cells produce estrogen and inhibin
• granulosa cells form a ring (corona radiata) around oocye and form mound *cumulus oophorus), together caled cumulus cells
• LH stimulates one graafian follicle> ovulation, others-->atresia

slight increase in FSH secretion from anterior pituitary

This FSH will circulate in blood, and combine with FSH receptor in granulosa cells. At this time, they are metabolically inactive, they are flat. There is only one layer surrounding granulosa. 

FSH binding to receptor stimulates more receptor to be expressed, so granulosa cells exhibit more FSH receptor, making granulosa cells more sensitive.

Pituitary FSH→↑in iFSH R' on granulosa cells→follicles more sensitive to FSH→↑# of granulosa cells→granulosa cells to produce estrogen (main form-estradiol E₂)→↑E₂ secretion to follicular fluid and blood

Towards the end of the phase:

FSH +E₂→↑LH R' on granulosa cells of graafian follicle

Rapid ↑in E₂ from granulosa cells →↑frequency of hypothalamic GnRH puleses →↑LH secretion

estrogen secr ↑ because of ↑ in # of gran cells. This stimulates # of LH receptors on gran cells. reach peak and start LH secretion from anterior pituitary (LH surge). Estrogen peak stimulates LH surge and LH surge stimulates ovulation.

What is cyclic change in ovary and how does that respond to ?
Negative feedback effect of steroid on pituitary.

Cyclic change of ovaries due to hypothalamus

• Risk of osteoporosis & CV diseases 
• Risk of endometrial and ovarian cancer 
• Prevent pregnancy at a higher success rate 
• Reduce cramping 
• May increase the risk for breast and cervical cancers

• Cessation of ovarian activity and menstruation 
• Ovaries are depleted of follicles 
• Menopause - ↑ FSH and ↑ LH, no E₂, P₄, inhibin secretion 
• E₂ and inhibin withdrawal ↑ hot flashes, and atrophy of the vaginal wall 

• ↑ risk of atherosclerotic cardiovascular diseases 
• ↑ risk of osteoporosis

• Excitation phase (arousal)
• Plateau phase
• Orgasm
• Resolution phase
• Refractory period

• Myotonia - increases muscle tone 
• Vasocongestion – engorgement of sexual organ 
• Nipples (esp. in female), clitoris, penis, labia minora 
• Vaginal secretion, producing lubrication

• A few seconds, men ejaculate & women have analogous contractions of uterus & vagina
• Equivalent to contraction that accompany ejaculation in male

• Occurs in male only, (+) erect, (-) ejaculate
• Females are capable of multiple orgasms

• Capacitation of sperm
• Fertilization
• Acrosomal reaction 
• Hardening of zona pellucida - avoid polyspermy 
• Completion of second meiosis in secondary oocyte

• First they bow (bended conformation)
• Then they take off their cap (called acrosome)
• They enter, causing a biochemical change in the outside of the egg called zona pellucida, making it harder. This prevents multiple sperms from fertilizing the egg (polyspermy)

• Inner cell mass - fetus 
• Surrounding chorion: 
• Trophoblasts form placenta

• D5~6 after fertilization - 10th wk of pregnancy 
• Secretion of hCG (LH-like), maintains corpus luteum, prevent menstruation 
• Implantation and fetal portion of placenta

• Has ability to create an entire organism, i.e. can differentiate into embryonic and extra-embryonic cell types 
• Fertilized egg cells & early cleavage cells only

• Stem cell that has the potential to differentiate into any of the three germ layers (endoderm, mesoderm, or ectoderm) 
• Alone cannot develop into an organism because they lack the potential to develop into extraembryonic tissue (trophoectoderm → placenta) 
• Embryonic stem cells (ESC) are pluripotent cells

• Fertilization occurs in fallopian tube 

•  Ejaculated sperms are infertile until in the female reproductive tract for > 7 hr 

• Genes from two individuals are combined in random ways to produce a new individual – variation and adaptability 
• Diploid vs. haploid chromosomes, mitosis and meiosis 
• Fertilization – germ cells (gametes) → zygote 
• zygote → embryo → fetus through growth and development

Determined by the fertilizing sperm cells

• XY: chromosomal sex is male
• XX: chromosomal sex is female

• X because it has 1,090 genes while Y has only 80 genes 
• The Y chromosome has many testis-specific genes 

• The inactive X chromosome in a female somatic cell 
• Can be seen on the nucleus of such as neutrophils

• Gonads remain indifferent until day 40 of conception in human fetus 
• Y chromosome contains sex-determining region in the Y chromosome (SRY) 
• SRY encodes testis-determining factor (TDF), which determines the gonadal sex of individual. 
• TDF is a transcription factor binding to DNA that enhances other transcription factors 
• TDF induces maleness through the formation of testes 
• TDF is essential to promote testis formation 
• Genetic (chromosomal) sex determines gonadal sex, which in turns uses hormones to determine phenotypic sex

• Development of testis 
• Seminiferous tubules (day 43-50) 
• Germinal cells – sperms 
• Sertoli cells (nongerminal cells) 
• Leydig cells – secrete testosterone (T) to: 
• Masculinizes embryonic structures 
• ↓ ↓ ↓ Secretion of T until puberty 
• Testes descend into scrotum shortly before birth 
• In the absence of SRY the bi-potential gonads develop into the default ovaries 
• This involves important factors that antagonize testis development 
• In female ovaries follicles don't appear until day 105

• Mullerian inhibition factor (MIF, MIH, AMH) 
• In male, MIF secreted from Sertoli cells of the seminiferous tubules → regression of the Mullerian ducts 
• In female, without MIF, Mullerian ducts developed into uterus & uterine tube 
• Testosterone and Wolffian ducts 
• In male, testosterone → growth and development of the Wolffian ducts into male sex accessory organs (epididymis, vas deferens, seminal vesicles, and ejaculatory duct) 
• Dihydrotestosterone (DHT) → penis, scrotum, prostate 
• In female, Wolffian ducts degenerate in the absence of testosterone

• Female accessory sex organs develop as a result of the absence of testes, rather than as a result of the presence of ovaries
• External genitalia
• External genitalia are same during 1st 6 wks
• External genitalia develops into male genotype due to testicular secretions
• In the absence of testis, female external genitalia is developed.
• Homologous structures
• Penis (♂) ↔ clitoris (♀)
• Scrotum (♂) ↔ labia majora (♀)

• True hermaphroditism 
• Presence of both ovary and testis in the body 
• Defects in Y  TDF production in some cells 
• Female pseudohermaphroditism 
• Congenital adrenal hyperplasia  ↑ androgen production  male genitalia 
• No MIF  maintains female internal genitalia (uterus and oviduct) 
• Male pseudohermaphroditism 
• Testicular feminization syndrome 
• No androgen R’  (+) female external genitalia, vagina ends blindly 
• Lack of 5a-reductase to convert T into DHT  (+) internal, ambiguous external ♂ genitalia

• Functions of sex steroids after puberty: 
• Stimulation of spermatogenesis or oogenesis 
• Secondary sexual characteristics 
• In girls – growth spurt, breast development, menarche (first menstrual flow) 
• In boys – occurs later; body, muscle, penis, and testis growth 
• In both sexes – body hair is stimulated by androgens from adrenal gland at puberty

• Structure of testis 
• Seminiferous tubules 
• Germinal epithelium – for spermatogeneisis 
• Sertoli cells – secrete inhibin, contain FSH receptors 
• Leydig cells - secrete T, contain LH receptors

Production of testosterone (endocrine) 

• Anabolic effects 
• Initiation and maintenance of body changes in puberty 
• Stimulates growth of muscles, larynx, and bone (until sealing of the epiphyseal discs) 
• Erythropoiesis – promote hemoglobin synthesis 
• Behavior effects – sexual behavior & others 

Production of sperms (spermatogenesis) 

• Regulated by testosterone & FSH 
• Testosterone for meiosis and early stage of sperm maturation; FSH for later stage of spermatid maturation 
• FSH-FSH R’ on Sertoli cells → ↑ LH R’ on Leydig cells → ↑ responsiveness to LH → ↑ T production 
• Paracrine regulators – TGF, IGF-1, inhibin

• Spermatogonia – replicate initially by mitosis 
• Each primary spermatocytes undergoes meiosis: 
• 1st meiotic division → 2 secondary spermatocytes 
• 2nd meiotic division → 4 spermatids 
• Spermiogenesis 
• Maturation of spermatozoa from spermatids 
• Phagocytosis of cytoplasm by the Sertoli cells – cytoplasm is eliminated

• Form blood-testes barrier: 
• Gap junctions 
• Prevents autoimmune destruction of sperm 
• Produce FAS ligand → binds to the FAS R’ on T cells → apoptosis of T cells → prevents immune attack 
• FSH + FSH R’ on Sertoli cells → secrete inhibin 
• Phagocytize residual bodies for maturation of spermatozoa 
• Secrete androgen-binding protein (ABP): 
• Binds to testosterone and concentrates testosterone in the tubules

• Epididymis (plural – epididymides) 
• A site for maturation and storage of sperm 
• Gains motility and resistance to pH and temperature changes 
• Ductus (vas) deferens 
• Carries sperm from epididymis into pelvic cavity 
• Seminal vesicles 
• Secrete fluid (45-80% of semen) containing fructose 
• Secrete prostaglandins 
• Prostate gland 
• Secretes alkaline fluid (15-30% of semen) rich in acid phosphatase, citric acid, Ca2+ 
• Semen – spermatozoa with fluids from seminal vesicles and prostate gland

• Controlled by cerebrum, hypothalamus and sacral region of spinal cord 
• Parasympathetic stimulation of erectile tissues 
• Vasodilation of arterioles, blood flow into the erectile tissues of the penis 
• Partial occlusion of venous outflow 
• NO as the neurotransmitter activates guanlyate cyclase → ↑ cGMP → closure of Ca2+ channels → vascular smooth m. relaxation → vasodilation → erection 
• Viagra etc. inhibit phosphodiesterase → ↓ breakdown of cGMP → promote erection 

• Movement of semen into urethra 
• Sympathetic stimulation → peristaltic contraction of the tubular system 

• Forcible expulsion of semen from the urethra out of penis 
• Sympathetic stimulation → contraction of testes, seminal vesicles, prostate & tubular smooth muscles 
• Normal volume - 1.5 ~ 5 ml, 60-150 x 106 sperm/ml ejaculate 
• < 20 x 106 sperm/ml is oligospermia

• Ovaries – follicles contain ova, corpus luteum (CL) 
• Uterus – horn, body and cervix, endometrium 
• Oviduct (uterine tube, fallopian tube) 
• Vagina and external genitalia 
• Labia majora, labia minora, clitoris, hymen 

• 5 months gestation – 6 - 7 x10⁶ oogonia 
• At late gestation – first meiosis (not complete) → primary oocytes (diploid) 
• At birth – 2 x 10⁶ primary oocytes 
• At puberty – 300,000 - 400,000 primary oocytes