Male and Female Reproductive Physiology

Male Reproductive Anatomy and the "SEVEN UP" Pathway

• SEVEN UP Mnemonic: A mnemonic used to describe the pathway of sperm through the male reproductive system.
      - S: Seminiferous tubules (located inside the testes where sperm is produced).
      - E: Epididymis (where sperm matures).
      - V: Vas deferens (a muscular tube carrying sperm).
      - E: Ejaculatory duct (formed by the union of the vas deferens and the seminal vesicle duct).
      - N: Nothing (placeholder).
      - U: Urethra (consisting of the prostatic urethra and the penile urethra).
      - P: Penis (the male copulatory organ).
• Testes (Testicles):
      - Paired Gonads: Suspended in an outpouching of the peritoneal cavity known as the tunica vaginalis.
      - Testicular Lobules: The testes are divided into lobules, each containing $1-4$ blindly-ending seminiferous tubules.
      - Scrotum: A musculocutaneous pouch composed of skin and dartos muscle that encases the testes.
      - Vasculature: Perfused by the testicular artery and drained by the pampiniform plexus of veins.
      - Temperature Regulation: Testes sit outside the body in the scrotum because they must be at a lower temperature ($~35^\circ \text{C}$) than the core body temperature ($37^\circ \text{C}$) for successful spermatogenesis.
• Prostate Gland and Clinical Context:
      - The male urethra passes through the prostate gland.
      - If the prostate becomes inflamed or cancerous, it restricts urine flow, leading to inability to urinate or improper flow.
      - Surgery on the prostate can lead to urinary incontinence.
      - The prostate is considered analogous to mammary tissue; while females are prone to breast cancer, males are prone to prostate cancer.

Thermoregulation of the Testes

• Regulating Muscles:
      - Dartos Muscle: Smooth muscle located in the scrotum. When it contracts, the scrotum shrivels, decreasing surface area for heat loss to retain heat.
      - Cremaster Muscle: Consists of smooth and skeletal muscle. When it contracts, it raises the testes toward the body for heat retention.
• Mechanism for Cooling:
      - Countercurrent Heat Exchange: The pampiniform plexus of veins absorbs heat from the testicular artery before blood reaches the testes, ensuring the blood is cooled to the necessary $~35^\circ \text{C}$.
• Anatomical Structures of the Scrotal Core:
      - Tunica Albuginea: The dense fibrous capsule of the testis.
      - Mediastinum Testis: The thickened part of the tunica albuginea that contains the rete testis.
      - Septa: Divide the testis into lobules.

Histology and Spermatogenesis

• Seminiferous Tubules:
      - Highly convoluted tubules, total length approximately $400\,m$.
      - Lined by seminiferous epithelium containing Sertoli cells and spermatogenic cells.
      - Surrounded by loose connective tissue containing Interstitial cells of Leydig.
• Sertoli Cells: Also known as "nurse cells," they support and protect developng sperm.
• Leydig Cells: Located in the interstitial space; they produce testosterone in response to LH.
• The Spermatogenesis Process:
      - Spermatogonium: Diploid ($2n$) germ/stem cell.
      - Primary Spermatocyte: Diploid ($2n$) cell undergoing Meiosis I.
      - Secondary Spermatocytes: Haploid ($1n$) cells resulting from Meiosis I; these undergo Meiosis II.
      - Spermatids: Haploid ($1n$) cells resulting from Meiosis II.
      - Spermiogenesis: The developmental process where spermatids transform into mature Spermatozoa.

Genital Ducts and Accessory Glands

• Intratesticular Ducts:
      - Tubuli recti: Straight tubules that transport sperm to the rete testis.
      - Rete testis: A network of tubules that collects and transports sperm.
      - Efferent ducts: Reabsorb Sertoli cell secretions to concentrate and compact sperm.
• Extratesticular Ducts:
      - Epididymis: Site where sperm reach motility, though they are incapacitated by the acidic pH found here.
      - Vas deferens: A muscular tube that propels sperm during ejaculation.
      - Ejaculatory duct: A short tubule that enters the prostate and opens into the prostatic urethra.
• Accessory Glands:
      - Seminal Vesicles ($~70\%$ of semen volume): Glands located above the prostate; they produce fructose-rich fluid ("sperm food") and semenogelins that coagulate semen upon ejaculation.
      - Prostate Gland ($~30\%$ of semen volume): Almond-sized gland producing fluid rich in $Zn^{2+}$ and $HCO_3^-$. It also secretes Prostate Specific Antigen (PSA), a protease that liquefies semen in the vagina. $Zn^{2+}$ initially inhibits PSA and aids in crosslinking semenogelins.
      - Bulbourethral (Cowper's) Glands: Secrete a thick, viscous pre-ejaculatory fluid that cleanses, lubricates, and neutralizes the acidity of the urethra.

Physiology of Erection and Ejaculation

• Penis Anatomy: Contains three columns of spongy erectile tissue: two dorsal columns (corpora cavernosa) and one ventral column (corpus spongiosum) which contains the penile urethra.
• Erection Mechanism:
      - Flaccid State: Increased Sympathetic Nervous System (SNS) activity causes blood to be shunted away from the erectile tissue via an arteriovenous (AV) shunt.
      - Erect State: Increased Parasympathetic Nervous System (PNS) activity and decreased SNS activity cause arterial dilation.
      - Molecular Pathway: PNS release of Nitric Oxide (NO) activates Guanylyl Cyclase (GC), which converts GTP to cGMP. High levels of cGMP lead to smooth muscle relaxation and blood filling the corpora cavernosa.
      - Phosphodiesterase (PDE): The enzyme that breaks down cGMP to end the erection. Drugs like Viagra (sildenafil) and Cialis (tadalafil) inhibit PDE to maintain cGMP levels.
• Ejaculation Phases:
      - Emission: Movement of semen into the urethra via rhythmic smooth muscle contractions of the epididymis, vas deferens, seminal vesicles, and prostate.
      - Expulsion: Discharge of semen from the penis; a spinal reflex causing rhythmic contractions of the bulbospongiosus, pelvic muscles, and urethral smooth muscle.

Male Reproductive Endocrinology

• Hypothalamic Maturation: Puberty (roughly age $9-14$) is driven by the maturation of the hypothalamus and the increased output of GnRH (Gonadotropin-Releasing Hormone).
• Gonadotropic Hormones:
      - FSH (Follicle-Stimulating Hormone): Stimulates Sertoli cells to drive sperm development (spermatogenesis) and produce Inhibin (which provides negative feedback to FSH).
      - LH (Luteinizing Hormone): Stimulates Leydig cells to produce Testosterone.
• Testosterone and Conversions:
      - Dihydrotestosterone (DHT): A more potent form converted in the prostate via $5\alpha$-reductase. Deficiency in this enzyme results in normal internal tract development but ambiguous external genitalia.
      - Estradiol: Converted from testosterone in Sertoli cells via aromatase, possibly to enhance spermatogenesis.
      - Plasma Levels: Testosterone levels peak at birth, drop during childhood, surge at puberty, and gradually decline during adult senescence.

Female Reproductive Anatomy and the Ovarian Cycle

• Ovaries: Paired gonads in the pelvic cavity, surrounded by germinal epithelium. The cortex contains developing eggs (oogenic cells), and the medulla contains loose connective tissue and vasculature.
• Ovarian Follicle Development:
      - Primordial Follicles: Primary oocyte arrested in Meiosis I surrounded by squamous follicular cells; developed in the absence of FSH.
      - Primary Follicles: Oocyte hypertrophies; follicular cells become cuboidal granulosa cells. Stromal cells form the theca interna (produces androstenedione) and theca externa.
      - Secondary Follicles: FSH-dependent. Granulosa cells stratify and secrete liquor folliculi (containing growth factors, estrogen, progesterone, and inhibin B).
      - Tertiary (Antral) Follicles: Characterized by the formation of a fluid-filled antrum. Granulosa cells differentiate into cumulus oophorous and mural granulosa.
      - Mature (Graafian) Follicles: Large antrum; secondary oocyte and cumulus cells float freely.
• Oogenesis:
      - Oogonia ($7$ million in utero) mitotically divide; only $~1$ million remain at birth; $~300,000$ remain at menarche.
      - Primary oocytes are arrested in Prophase I until puberty.
      - Secondary oocytes are arrested in Metaphase II until fertilization.

Ovulation and the Corpus Luteum

• Ovulation: Occurs on the $14^{th}$ day before menstruation. High estrogen triggers an LH surge.
• LH Surge Effects:
      - Resumption of meiosis (Meiosis I completes, Meiosis II begins and arrests).
      - Formation of a stigma (rupture point) on the ovarian surface.
      - Release of the secondary oocyte.
• Corpus Luteum: Formed from the collapsed Graafian follicle.
      - Granulosa-lutein cells: Produce progesterone and convert androgens to estrogens.
      - Theca-lutein cells: Produce progesterone and androgens.
      - Degeneration: Progesterone eventually inhibits LH, causing the corpus luteum to degenerate into a corpus albicans unless maintained by hCG from a pregnancy.

The Uterus, Fallopian Tubes, and Vagina

• Vagina: Copulatory organ lined with nonkeratinized stratified squamous epithelium. Semen coagulates here ($Zn^{2+}$) then liquefies as PSA activates to permit sperm entry into the cervix.
• Uterus: Pear-shaped organ with three layers: perimetrium, myometrium (muscle), and endometrium (glands/vasculature).
• Fallopian Tubes (Oviducts): Contain ciliated cells to move the ovum and peg cells to secrete nutrients and capacitation inducers like $HCO_3^-$.
• Fertilization and Implantation:
      - Fertilization: Typically occurs in the ampulla within $1-2$ days of ovulation.
      - Implantation: The embryo implants in the endometrium within $5-7$ days of fertilization.
      - Fertility Window: Peak fertility occurs approximately $2$ days prior to and on the day of ovulation.

The Menstrual Cycle and Clinical Conditions

• Phases:
      - Follicular Phase: Days $1-14$, dominated by FSH and increasing Estrogen.
      - Luteal Phase: Days $14-28$, dominated by Progesterone from the corpus luteum.
      - Uterine Cycle: Includes the Menstrual phase (shedding), Proliferative phase (regrowth), and Secretory phase (secretion for potential embryo).
• Contraception and Interruption:
      - The Pill: Uses hormones to suppress ovulation.
      - Plan B: Emergency contraception.
      - RU-486: Medication used for medical abortion.
• Clinical Pathologies:
      - Endometriosis: Growth of endometrial tissue outside the uterus, often due to retrograde menstruation.
      - Polycystic Ovarian Syndrome (PCOS): Characterized by multiple ($\ge 20$) antral follicles seen on ultrasound, rather than one dominant follicle.