Wagner-Male Reproductive Physiology

Front 1

Describe anatomical considerations of the male reproductive system

Back 1

1. Primary reproductive organs (gonads)-testes (contain 800 feet seminiferous tubules)
2. Reproductive tract-continuous system of ducts includes epididymis, vas deferens, ejaculatory duct and urethra
3. Accessory sex glands-include seminal vesicles, prostate gland and bulbourethral (Cowper’s) glands that produce secretions comprising bulk of semen
4. External genitalia-scrotum and penis
5. Secondary sexual characteristics-inherent external features in men (i.e., body configuration, hair distribution) not directly tied to reproduction but distinguishes males from females

Front 2

describe the role of the Leydig cell and the biodistribution of testosterone as they relate to testicular function

Back 2

Secretion of testosterone-C19 (19-carbon) 17-hydroxysteroid
a. Leydig cell-expresses full complement of enzymes necessary for testosterone synthesis (most notably 17α-hydroxylases)
b. biodistribution of testosterone-vast majority (98%) circulates in plasma bound to protein, 2/3 bound to gonadal steroid-binding globulin (GBG, aka sex steroid-binding globulin), w/ remaining 1/3 bound to albumin
Most free testosterone is converted to 17-ketosteroids such as androsterone and etiocholanolone, while small amounts are aromatically converted to estradiol

Front 3

describe the functions of testosterone

Back 3

i. in utero-masculinization of reproductive tract and external genitalia (latter is DHT-dependent); promotion of testicular descent through inguinal canal into scrotum; prolonged testicular retention w/in pelvic cavity known as cryptorchidism; descent induced by administration of steroid
ii. reproductive effects-promotes growth, maturation and maintenance of reproductive system at all developmental stages; essential for spermatogenesis, sexual libido, and control of gonadotropin secretion
iii. effects on secondary sexual characteristics-induces DHT-dependent male pattern of hair growth (i.e., beard growth, temporal hairline recession), and deepens voice enlarging larnyx and thickening vocal cords; exerts anabolic effect resultsing in increase in protein synthesis and muscle growth responsible for male body configuration
iv. other effects-stimulates pubertal bone growth, and DHT-dependent oil production from sebaceous glands

Front 4

describe the mechanism of androgen action

Back 4

testosterone binds to intracellular androgen receptor, and exerts physiological effects by regulating gene transcription and protein synthesis; in tissues that express 5α-reductase, DHT binds androgen receptor to ultimately influence gene transcription and cell function

Front 5

describe the mitotic proliferation and meiosis and how they relate to spermatogenesis

Back 5

Spermatogenesis-continuous process by which diploid germ cells are converted into highly specialized motile, haploid spermatozoa (process occurs over 3 stages)
a. mitotic proliferation-spermatogonia reside inside basal lamina of seminiferous tubule, and undergo continuous mitotic division; spermatogonium may give rise to 4 primary spermatocytes; once primary spermatocytes are formed, chromosomal duplication and tetrad formation takes place in preparation for 1st meiotic division
b. meiosis-1st meiotic division results in 2 secondary spermatocytes, each containing 23 duplicated chromosomes; 2nd meiotic division yields 2 spermatids, each w/ 23 chromatids; no further cell division takes place beyond this point

Front 6

describe packaging as it relates to spermatogenesis

Back 6

process by which spermatids are transformed into spermatozoa (aka spermiogenesis)
Gap jnxs that link secondary spermatocytes and spermatids together allows diffusion of gene products encoded by X chromosome essential for final sperm development to diffuse into spermatids bearing only Y chromosomes; ensures synchronous differentiation in each clone of germ cells
During spermiogenic remodeling, spermatids lose much of their cytoplasm and intracellular organelles; results in spermatozoa consisting of 4 parts: head, acrosome, midpiece and tail
head contains nucleus; acrosome surrounds head and is filled w/ enzymes for penetration of ovum during fertilization; midpiece contains mitochondria that supply energy required for microtubule displacement w/in tail, which gives spermatozoon its inherent motility

Front 7

describe the role of Sertoli cells in spermatogenesis

Back 7

large, glycogen-filled cells that stretch from basal lamina to lumen of seminiferous tubule; bound together by tight jnxs, allow maturing germ cells to migrate toward lumen in b/t them
i. help to form “blood-testis” barrier-tight jxns b/t adjacent Sertoli cells limit passage of plasma constituents into lumen of seminiferous tubule, and protect highly specialized spermatozoa from autoimmune attack
ii. provide nutritional assistance-developing germ cells don’t have full access to plasma nutrients
iii. perform phagocytic function-process intracellular contents cast aside during spermiogenesis, and also destroy defective germ cells
iv. secrete seminiferous tubule fluid, androgen-binding protein and inhibin
seminiferous tubule fluid helps flush spermatozoa from tubular lumen into epididymis; androgen-binding protein sequesters testosterone w/in tubular lumen; inhibin decreases gonadotropin secretion

Front 8

describe the effect of temperature on spermatogenesis

Back 8

testes maintained at temperature of 32C; essential for spermatogenesis, due to closer exposure to ambient environment, as well as countercurrent heat exchange mechanism b/t spermatic A & V; explains why cryptorchid is unable to produce viable sperm
Sterility clinically defined as having sperm count lower than 20 million/ml semen; average sperm count of 70-100 million/ml semen
Testicular position can be modified through spinal reflexes; exposure to cold causes a reflexive contraction of scrotal musculature, whereas warmer temperatures cause reflexive relaxation

Front 9

describe the male reproductive tract

Back 9

Reproductive tract-stores and concentrates maturing spermatozoa; delivers sperm to female reproductive tract
a. epididymis-maturing sperm moved through epididymis via rhythmic smooth muscle contractions; epididymis concentrates sperm 100-fold by absorbing majority of luminal fluid
b. vas deferens-duct runs back through inguinal canal and into pelvic cavity, where it empties into ejaculatory duct; serves an important sperm storage site; sperm are highly concentrated, relatively inactive, and can survive for days on simple sugars secreted into tubular lumen
c. ejaculatory duct-short segment of duct that joins urethra
d. urethra-final conduit of reproductive tract that carries sperm out penis during ejaculation

Front 10

describe the male accessory sex glands

Back 10

exocrine glands contribute secretions that promote sperm viability; collectively make up majority of semen
a. seminal vesicles-secrete fructose, prostaglandins and fibrinogen
b. prostrate gland-secretes alkaline fluid that serves to neutralize acidic vaginal secretions and enhance sperm viability
secretes enzymes that convert fibrinogen secreted from seminal vesicles into fibrin; this clotting action serves to keep sperm w/in female reproductive tract during withdrawal of penis
also secretes fibrinolysin, which dissolves fibrin clot, thereby releasing motile sperm w/in female reproductive tract
c. bulbourethral (Cowper’s) glands-secrete mucus that provides lubrication during sexual intercourse

Front 11

describe how the hypothalamus controls testicular function

Back 11

gonadotropin-releasing hormone (GnRH)-hypothalamic neurons synthesize and secrete GnRH release peptide hormone into hypophysial portal vasculature, where it's carried to anterior pituitary gland and stimulates secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH); GnRH is secreted in bursts that occur every 2-3 hours; these pulses of GnRH release lead to similar episodic bursts of FSH and LH secretion

Front 12

describe how the pituitary controls testicular function

Back 12

a. FSH-glycoprotein hormone acts on seminiferous tubule to promote spermatogenesis
Sertoli cells express serpentine receptor on plasma membrane that's coupled to Gs that increases activity of adenylyl cyclase; facilitates spermatid remodeling during spermiogenesis
b. LH-similar in structure to FSH, but exhibits shorter half-life in plasma and more pronounced pulsatility; stimulates synthesis and secretion of testosterone from Leydig cells
activates Gs-coupled plasma membrane receptor that stimulates adenylyl cyclase activity and increases intracellular cAMP levels; subsequent activation of protein kinase A stimulates formation of cholesterol from cholesterol esters via cholesterol ester hydrolase

Front 13

describe how gonads control testicular function

Back 13

a. inhibin-glycoprotein secreted by Sertoli cell in response to FSH that inhibits release of FSH from anterior pituitary gland
b. testosterone-acts in concert w/ FSH to promote spermatogenesis; acts on Sertoli cell, involved in spermatid maturation, and may also aid mitotic proliferation and meiotic divisions
provides negative feedback by inhibiting hypothalamic GnRH release and LH secretion from anterior pituitary
c. estrogenin males, estrogen produced in small quantities via aromatization of testosterone and androstenedione synthesized w/in testes and adrenal cortex; some testosterone w/in seminiferous tubule is converted to estradiol by Sertoli cells that express aromatase enzyme
estrogen receptors in testes, prostate and male central nervous system

Front 14

describe disruption of the reproductive axis

Back 14

a. hypergonadotropic hypogonadism-primary testicular deficiency characterized by reduced levels of testosterone (and inhibin), and elevated levels of GnRH and gonadotropins (due to loss of negative feedback)
b. hypogonadotropic hypogonadism-testicular deficiency arises from either reduced sensitivity of anterior pituitary to stimulatory effect of GnRH, or reduced hypothalamic output of GnRH itself; resulting in significant reduction in circulating gonadotropin levels (example is Kallmann’s syndrome-GnRH neurons fail to migrate into hypothalamus during embryonic development)

Front 15

describe the onset of puberty

Back 15

Puberty-period of arousal and maturation of reproductive system, culminating in sexual maturity and ability to reproduce
control of onset-from neonatal period until puberty, essentially no testosterone secretion (attributed to exquisite sensitivity of hypothalamic GnRH neurons to both hormonal and neural inhibition)
onset of puberty triggered by nocturnal increase in GnRH pulse generator occurring b/t ages of 9-14; as testosterone levels rise, inherent secondary sexual characteristics and reproductive maturation become evident
most important determinant is reduced sensitivity to negative feedback actions of testosterone; hypothalami of prepubertal children are 6-15 times more sensitive to steroidal negative feedback

Front 16

describe precocious and delayed/absent puberties

Back 16

precocious puberty-early development of secondary sexual characteristics and spermatogenesis; most frequent symptom of hypothalamic disease (lesions of ventral hypothalamus); tumors of pineal gland associated and mutations in Gs protein that facilitate coupling of LH receptors to adenylyl cyclase are also causes
c. delayed or absent puberty-pathological delay in onset of puberty (failure of testicular development by age of 20)
hypopituitarism can cause maturation failure, as can Kallmann’s syndrome and childhood onset Leydig cell deficiency (eunuchoidism)
Eunuchoids have body configuration resembling adult female; external genitalia are small and voice high-pitched; pubic and axillary hair are present in sparse amounts, due primarily to adrenocortical androgen secretion

Front 17

describe andropause

Back 17

gradual decline in male reproductive function that occurs b/t ages 50-70; as andropause progresses, testosterone production and libido decrease; shrinkage of penis, scrotum and seminal vesicles, and decline in facial hair growth, muscle mass and strength; voice pitch increased, increased incidence of osteoporosis Andropause due to decreased responsiveness of testes to stimulatory effects of FSH and LH; related to decrease in testicular blood flow, and consequent damage to the seminiferous tubules
Gonadotropin levels increase over course of andropause due to loss of negative feedback by testosterone; androgen replacement therapy can restore libido, external genitalia, accessory sex glands, secondary sex characteristics, and protect against osteoporosis