Lecture 3: Male Reproductive System

Study Notes

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.

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.

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:
- < 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:
- 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.

↑ 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.

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.

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.

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.

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:
- 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.