Reproductive anatomy and physiology

• Venous drainage:
• -Left ovary/testis → left gonadal vein → left renal vein → IVC
• **Just as left adrenal vein drains to left renal vein
• **flow is less continuous on the left than on the right → L venous pressure > R venous pressure: Varicocele more common on the left
• -Right ovary/testis → right gonadal vein → IVC

• Lymphatic drainage:
• -Ovaries/testes → para-aortic lymph node
• -Distal 1/3 of vagina/vulva/scrotum → superficial inguinal nodes
• -Proximal 2/3 of vagina/uterus → obturator, external iliac and hypogastric nodes

• Connects: ovaries to lateral pelvic wall
• Contains: ovarian vessels
• Ureter at risk of injury during ligation of ovarian vessels in oophorectomy
• *Suspensory ligament suspends ovary to pelvic wall

• Connects: Cervix to side wall of pelvis
• Contains: uterine vessels
• Ureter at risk of injury during ligation of uterine vessels in hysterectomy

• Connects: Uterine fundus to labia majora
• Contains: Artery of Sampson
• Derivative of gubernaculum
• Travels through round inguinal canal

• Connects: Uterus, fallopian tubes, and ovaries to pelvic side wall
• Contains: Ovaries, fallopian tubes, round ligament of the uterus
• *Mesosalpinx, mesometrium, and mesovarium are the components of the broad ligament

• Connects: Medial pole of ovary to lateral uterus
• Contains: none
• Ligametn of the ovary Latches ovary to Lateral uterus
• Derivative of the gubernaculum

• Vagina: Stratified squamous epithelium, nonkeratinized
• Ectocervix: Stratified squamous epithelium
• Endocervix: Simple columnar epithelium
• Uterus: Simple columnar epithelium, pseudostratified tubular glands
• Fallopian tube: Simple columnar epithelium, ciliated
• Ovary: Simple cuboidal epithelium

• SEVEN UP:
• Seminiferous tubules
• Epididymis
• Vas deferens
• Ejaculatory ducts
• (Nothing)
• Urethra
• Penis

• Erection:
• Parasympathetic nervous system (pelvic nerve):
• -NO → ↑cGMP → smooth muscle relaxation → vasodilation → proerectile
• -NE → ↑ [Ca²⁺]_in → smooth muscle contraction → vasoconstriction → antierectile

Emission: Sympathetic nervous sytem (hypogastric nerve)

Ejaculation: visceral and somatic nerves (pudendal nerve)

Point and Shoot

Sildenafil and vardenafil inhibit cGMP breakdown

• Spermatogonia (germ cells)
• Sertoli cells (non-germ cells)
• Leydig cells (endocrine cells)

• Maintain germ pool
• Produce 1° spermatocytes
• Line seminiferous tubules
• 

• Function:
• -Secrete inhibin → inhibit FSH
• -Secrete androgen-binding protein (ABP) → maintain local levels of testosterone
• -Tight junctions between adjacent Sertoli cells form blood-testis barrier → isolate gametes from autoimmune attack
• -Support and nourish developing spermatozoa (Italian nurses)
• -Regulate spermatogenesis
• -Produce anti-müllerian hormone
• -Temperature sensitive: ↓ sperm production and ↓ inhibin with ↑ temperature
• **↑ temperature with varicocele, cryptorchidism

• Location:
• -Line seminiferous tubules

Sertoli cells Support Sperm Synthesis

• Secrete testosterone
• *Testosterone production unaffected by temperature
• Location: interstitium

• Begins at puberty with Spermatogonia
• Full development takes 2 months
• Occurs in seminiferous tubules
• Produces Spermatids → spermiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature Spermatozoon

**"Gonium" is going to be sperm; "Zoon" is "Zooming" to egg

• Impaired tail mobility can lead to infertility
• -Ciliary dyskinesia
• -Kartagener's syndrome

Spermatid haploid goes on to become mature spermatozoon haploid (N)

• Testis:
• -Testosterone
• -Dihydrotestosterone (DHT)

• ADrenal:
• -AnDrostenedione

Potency: DHT > testosterone > androstenedione

• -Differentiation of epididymis, vas deferens, seminal vesicles (internal genitalia, except prostate)
• -Growth spurt: Penis, seminal vesicles, sperm, muscle, RBCs
• -Deepening of voice
• -Closing of epiphysial plates (via estrogen converted from testosterone)
• -Libido

• -Early: differentiation of penis, scrotum, prostate
• -Late: prostate growth, balding, sebacious land activity

Testosterone → DHT by 5α-reductase, inhibited by finasteride

• Testosterone and androstenedione  → estrogen in adipose tissue and Leydig cells by the enzyme aromatase
• -(Aromatse is the key enzyme in the conversion of androgens to estrogen)

Exogenous testosterone → inhibition of hypothalamic-pituitary-gonadal axis → ↓ intratesticular testosterone  → ↓ testicular size  → azoospermia

• Ovary: 17β-estradiol
• Placenta: estriol
• Adipose tissue: estrone
• ---Potency: Estradiol > estrone > estriol
• ---Estrogen receptor expressed in cytoplasm; translocates to nucleus when bound by ligand

• -Development of genitalia and breast, female fat distribution
• -Growth of follicles, endometrial proliferation, ↑ myometrial excitability
• -Upregulation of estrogen, LH, and progesterone receptors; feeback inhibition of FSH and LH, then LH surge; stimulation of prolactin secretion (but blocks its action at breast)
• - ↑ transport proteins, SHBG; ↑ HDL; ↓ LDL

• 50-fold ↑ in estradiol and estrone
• 1000-fold ↑ in estriol (indicator of fetal well-being)

• Source:
• -corpus luteum
• -placenta
• -adrenal cortex
• -testes

• Function:
• -Stimulation of endometrial glandular secretions and spiral artery development
• -Maintenance of pregnancy
• - ↓ myometrial excitability
• -Production of thick cervical mucus, which inhibits sperm entry into the uterus
• - ↑ body temperature
• - Inhibition of gonadotropins (LH, FSH)
• - Uterine smooth muscle relaxation (preventing contractions)
• - ↓ estrogen receptor expressivity

• **Elevation of progesterone is indicative of ovulation
• **Progesterone is pro-gestation

• I. Childhood
• II. Pubic hair appears (pubarche); breast bud form (thelarche)
• III. Pubic hair darkens and becomes curly; penis size/length ↑; breasts enlarge
• IV. Penis width ↑, darker scrotal skin, development of glans; raised areolae
• V. Adult; areolae are no longer raised

• Follicular phase can vary in lenth
• Luteal phase is constant: 14 days
• Ovulation day + 14 days = menstruation
• Folicular growth: fastest during 2nd week of proliferative phase
• Estrogen: stimulates endometrial proliferation
• Progesterone: maintains endometrium (for implantation)
• **↓ Progesterone means ↓ fertility

• Oliogmenorrhea: >35 day cycle
• Polymenorrhea: <21 day cycle
• Metrorrhagia: frequent but irregular menstruation
• Menometrorrhagia: heavy, irregular menstruation at irregular intervals

• ↑ estrogen, ↑ GnRH receptors on anterior pituitary
• Estrogen surge then stimulates LH release, causing ovulation (rupture of follicle)
• ↑ temperature (progesterone induced)

Blood from ruptured follicle or follicular enlargement cause peritoneal irritation that can mimic appendicitis

• 1° oocyte begin in meiosis I during fetal life
• Complete meiosis I just prior to ovulation: arrested in prOphase I for years until Ovulation (1° oocyte)
• Meiosis II is arrested in metaphase II until fertilization (2° oocytes) **An egg met a sperm
• If fertilization does not occur within 1 day, the  2° oocyte degenerates

• Fertilization: most commonly occurs in upper end of fallopian tube (ampula)
• -Occurs within 1 day of ovulation

Implantation: day 6 post fertilization

• Detection: trophoblasts secrete hCG
• -detectable in blood 1 week after conception 
• -in urine: 2 weeks after conception

• After labor: ↓ in progesterone disinhibits lactation
• Suckling is required to maintain milk production
• ↑ nerve stimulation ↑ oxytocin and prolactin
• Prolactin: induces and maintains lactation and ↓ reproductive function
• Oxytocin: appears to help with milk let down; may be involved in uterine contractions

Source: Syncytiotrophoblast of placenta

• Function: Maintains the corpus luteum (and thus progesterone) for 1st trimester by acting like LH
• 2nd, 3rd trimetsers: placenta synthesizes its own estriol and progesterone; corpus luteum degenerates

• Elevated hCG: pathologic states
• -hydatidiform mole
• -Choriocarcinoma

• ↓ estrogen production
• Due to age-linked decline in number of ovarian follicles
• average age: 51 (earlier in smokers); <40 indicates premature ovarian failure
• Preceded by 4-5 years of abnormal cycles
• Estrone becomes main source; ↑ androgens cause hirsutism
• ↑↑ FSH is the best test to confirm menopause (loss of negative feedback for FSH due to ↓ estrogen)

• ↓ estrogen
• ↑↑ FSH
• ↑ LH (no surge)
• ↑ GnRH

• HHAVOC:
• Hirsutism
• Hot flashes
• Atrophy of the Vagina
• Ostoporosis
• Coronary artery disease