Lecture 3: Male Reproductive System

Male Reproductive System

• The conversion of testosterone to dihydrotestosterone via 5α-reductase is necessary for the formation of the prostate gland and male external genitalia.
• During fetal development:
  • Genital folds fuse to form the penis.
  • Labioscrotal swellings form the scrotum.
  • Descent of the fetal testes into the scrotum requires the secretion of fetal gonadotropins and occurs during the last trimester of pregnancy.
• Puberty begins with the activation of the GnRH pulse generator within the hypothalamus, stimulated by kisspeptin, which stimulates GnRH neurons.
• In complete androgen insensitivity syndrome (CAIS), a lack of functional androgen receptors leads to:
  • 46,XY DSD (disorder of sexual development).
  • Testes remaining undescended.
  • Müllerian-inhibiting substance continues to be secreted from Sertoli cells, resulting in the absence of female internal genitalia.
  • Dihydrotestosterone is made but cannot direct the Wolffian duct to develop into male genitalia due to the lack of androgen receptors; individuals have female external genitalia.

Testes and Spermatogenesis

• Spermatogonia, precursors of male gametes, give rise to spermatocytes, which undergo meiosis to form sperm.
• Leydig cells secrete testosterone, stimulated by LH from the anterior pituitary gland.
• FSH from the anterior pituitary gland stimulates Sertoli cells, which support spermatogenesis.
• Inhibin, produced by Sertoli cells, inhibits FSH production to regulate spermatogenesis.

Kallmann Syndrome and Kleinfelter Syndrome

• Kallman syndrome:
  • Gene defect leading to a lack of GnRH neurons.
  • X-linked inheritance.
  • Hypogonadotropic hypogonadism, with decreased or absent sense of smell (anosmia).
• Klinefelter syndrome (47, XXY):
  • Most common chromosomal disorder associated with infertility.
  • Small testes and low testosterone levels.
  • Puberty is often delayed or incomplete.

Epididymitis, Orchitis, and Testicular Torsion

• Epididymitis:
  • < 35 yo: Chlamydia/Gonorrhea.
  • > 35 yo: E. coli.
  • Associated with UTI and BPH.
• Orchitis:
  • Mumps infection.
• Testicular Torsion:
  • Absent cremasteric reflex.
  • Bell clapper deformity: a tender, enlarged, high-riding testis, with its long axis oriented transversely due to the shortening of the spermatic cord.

Varicocele and Cryptorchidism

• Varicocele:
  • Most common cause of subfertility in men.
  • Possible pathogenic mechanisms: anatomical configuration of the left internal spermatic vein, incompetent or absent valves, and potential compression of the left renal vein.
• Cryptorchidism:
  • Associated with testicular malignancy, infertility, inguinal hernia, and torsion.
  • Unilateral: risk of impaired sperm production or becoming malignant.

Benign Prostatic Hyperplasia (BPH)

• ↑ 5α-reductase and DHT levels with age.
• ↑ PSA.
• Pathophysiology: DHT binds to and activates androgen receptors in both stromal and epithelial prostate cells.
• Symptoms: chronic lower UT symptoms, symmetrically enlarged, smooth, firm, non-tender prostate with a rubbery texture.

Female Reproductive System

• Development of female genitalia:
  • Labia minora forms from genital folds.
  • Clitoris forms anterior to the urethral opening.
  • Labia majora formed from labioscrotal swellings.
• Ovarian steroid secretion occurs in response to FSH and LH.
• LH surge initiates ovulation.
• Damage to uterine ligaments (e.g., during childbirth) may result in prolapse of the uterus downward into the vagina.

Menstrual Cycle

• Follicular phase (days 1-14):
  • Estrogen secretion by granulosa cells.
  • Inhibin secretion under the influence of FSH.
  • Androgens from thecal cells are used as a substrate for estrogen production.
• Luteal phase (days 15-28):
  • Progesterone secretion by the corpus luteum.
  • Estrogen and progesterone levels peak around ovulation.

Placenta and Hormones

• Placental peptides:
  • hCG (rescues the corpus luteum from degeneration and allows continued progesterone secretion to support the early pregnancy).
  • hCS (supports the early pregnancy).
• Decidualization: the entire endometrium undergoes biochemical and morphologic change, forming the "membranes of pregnancy" called the decidua.

Lactation

• Proteins make up about 1% of milk; casein and lactalbumin are only found in milk.
• Colostrum:
  • Produced within the first few days after parturition.
  • Contains more protein than milk, including antibodies and immune cells, and provides the neonate with some immunologic protection.
• Prolactin and oxytocin are the two key hormones involved in the control of lactation.

Infertility and Turner Syndrome

• Infertility:
  • Most common factor: anovulatory menstrual cycles.
  • Common causes: polycystic ovarian syndrome, thyroid dysfunction, and stress.
• Turner syndrome (45, XO):
  • Lack one of the X chromosomes.
  • Rudimentary "streak" ovaries.
  • Inability to undergo puberty without hormone therapy.