27. Male Reproductive Physiology Flashcards
Describe the Hypothalamic-pituitary-testicular axis in terms of hormones released
Hypothalamus = GnRH
Anterior pituitary = FSH, LH
Testes = testosterone, inhibin
Describe negative feedback via HPT axis
Testosterone from testes inhibits GnRH and LH from H and AP
Inhibin and estradiol inhibit FSH and GnRH
What 4 physiological processes are controlled by the hypothalamic-pituitary-testicular axis?
Phenotypic gender (embryogenesis)
Sexual maturation (puberty)
Testosterone production
Sperm production
What is the difference between genetic sex, gonadal sex, and phenotypic sex?
Genetic sex = XY vs. XX
Gonadal sex = testes vs. ovaries
Phenotypic sex = internal and external genitalia
What hormones determine phenotypic sex?
Antimullerian hormone and testosterone (presence = male, absence = female)
80% of the testes composition is _____ ______, which produce sperm
Seminiferous tubules
What cell types are found in the seminiferous tubules?
Sertoli cells (supportive)
Spermatogonia (stem cells)
Spermatocytes (developing sperm)
If seminiferous tubules make up 80% of the testes, what makes up the other 20%?
Connective tissue/interstitium
What cell types are found in the CT/interstitium of the testes?
Leydig cells — produce testosterone
Also mast cells, macrophages, nerves, blood vessels, lymph vessels
In terms of hormonal control, Leydig cells are stimulated by _____, and sertoli cells are stimulated by ____
LH; FSH
2 Exocrine functions of the sertoli cells
Secrete aqueous fluid into lumen of seminiferous tubules —> sperm transport from tubules to epididymis
Produce androgen-binding protein —> binds testosterone and concentrates it in seminiferous tubules
In terms of endocrine function of the sertoli cells, what 3 hormones do they produce?
Antimullerian hormone
Inhibin
Aromatase
Action of antimullerian hormone produced by sertoli cells
Regression of internal femal genital ducts
Action of inhibin produced by sertoli cells of testes
Inhibits FSH
Action of aromatase produced by sertoli cells of the testes
Converts testosterone to estradiol-17B
What are the supportive functions of sertoli cells of the testes?
Provide nutrients to differentiating sperm (transferrin, Fe, lactate)
Form tight junctions (blood testes barrier)
Leydig cells synthesize and secrete testosterone. They can make their own ______ de novo, or acquire it from circulation
Cholesterol
How does GnRH secretion change at puberty? What effects does this have on the rest of the HPT axis?
GnRH from hypothalamus becomes pulsatile —> pulsatile FSH and LH secretion from AP —> sex steroid hormon secretion (e.g., testosterone)
What are the 3 primary androgens?
Testosterone
Dihydrotestosterone (DHT)
Androstenedione
Androgens bind androgen receptors in reproductive and non-reproductive tissues with varying affinity. Which androgen has the highest affinity in males?
DHT has the highest, followed by testosterone, then androstenedione
______ is an active androgen in MOST androgenic target tissues?
Testosterone
Testosterone is made in Leydig cells. Where does it go from there?
To seminiferous tubules —> peritubular capillaries —> peripheral circulation
Testosterone binds _____ _____ _____in the seminiferous tubules, which leads to its concentration
Androgen-binding protein (ABP)
Testosterone binds various proteins in peripheral circulation — what proteins does it primarily bind to and which of these allow it to be biologically active?
60% binds sex hormone binding globulin (SHBG) = inactive
38% binds albumin = weakly active
2% is free T = biologically active!
Testosterone production begins at 7-8 weeks gestation. What are its initial roles in development?
Stimulates formation of internal male genitalia (epididymis, vas deferens, seminal vesicles), penis, scrotum
Also stimulates testicular descent
Testosterone leads to the development of what secondary sex characteristics at puberty?
Growth spurt Closure of epiphyseal plates Acne Increased muscle mass Deepening of voice Body hair Baldness Libido Growth of penis and seminal vesicles Increased BMR Increased RBCs
What aspect of sperm development is stimulated by testosterone?
Spermatogenesis
What enzyme is responsible for the conversion of testosterone to DHT in target tissues?
5-alpha-reductase
T/F: testosterone is an active androgen in most androgenic target tissues, while DHT is only active in some
True
What role does DHT play during development?
Stimulates development of external male genitalia (penis, scrotum, prostate)
What role does DHT play during puberty?
Sebaceous gland activity
Prostate growth
What hormone is often considered responsible for male pattern baldness?
DHT
The pathogenesis of BPH is poorly understood, but requires androgens, especially ____
DHT
BPH causes enlargement of periurethral prostate lobes, which compress the urethra. This leads to what type of storage and voiding symptoms?
Urinary frequency and urgency, slow stream, dribbling after urination
T/F: BPH often represents a malignant process
False - it is NOT premalignant!
What are 1st and 2nd line tx for BPH?
1st line = alpha-1 antagonists which relax smooth muscle in bladder neck and urethra
2nd line = 5-alpha reductase inhibitors which block conversion of testosterone to DHT (less DHT = less hyperplasia)
Testosterone can be aromatized to estrogens like estradiol in peripheral tissues and sertoli cells. What actions does this have in males?
Bone maturation
Growth acceleration
Breast growth
Role in spermatogenesis
In general, male hypogonadism refers to a decrease in ____ and/or _____ production
Sperm/testosterone
In ______ hypogonadism, or Klinefelter syndrome, the pt is born with ______ chromosome profile, meaning that they have a ____ phenotype
Primary; 47 XXY; male (bc they have Y chromosome)
What effect does primary hypogonadism have on testis function?
Abnormal Leydig cell function — low testosterone production —> high LH —> high estrogen
Seminiferous tubule dysgenesis —> infertility, decreased inhibin leads to high levels of FSH
Causes of secondary hypogonadism
Nonfunctioning pituitary tumors
Kallmann syndrome
Symptoms of secondary hypogonadism d/t nonfunctioning pituitary tumors
Pituitary compression leads to low LH and FSH production —> low testosterone —> hypogonadism
Mass effect = visual symptoms, headache
Pathogenesis of Kallmann syndrome leading to secondary hypogonadism
GnRH neurons fail to migrate into hypothalamus during embryonic development —> low GnRH secretion —> low LH, FSH —> low testosterone
Symptoms of secondary hypogonadism due to Kallmann syndrome
Delayed/absent puberty
Infertility
Impaired sense of smell (anosmia)
Spermatogenesis occurs in the __________, beginning at _____ and continuing throughout life
______ are the immature germ cells present at birth that will undergo this process
Seminiferous tubules; puberty
Spermatogonia
What are the 3 phases of spermatogenesis?
Mitotic division
Meiotic division
Spermiogenesis
Phase 1 of spermatogenesis = mitotic division
This phase starts with _______, the immature germ cells which will undergo mitosis to produce ________
Spermatogonia
2 primary spermatocytes
Phase 2 of spermatogenesis = meiotic divisions
This phase starts with ___________ which undergo 2 meiotic divisions. The first division produces ________, each with a _____ number of duplicated chromosomes
The second division produces ________, each with a _____ number of unduplicated chromosomes
Primary spermatocytes; 2 secondary spermatocytes; haploid
2 spermatids; haploid
Phase 3 of spermatogenesis = spermiogenesis
This phase starts with ________ which undergo nuclear and cytoplasmic changes to produce mature ______
Spermatids; spermatozoa
T/F: the entire process of spermatogenesis takes about 25 days
False; it takes ~74
What are the functional parts of the sperm?
Head = fertilization
Tail = motility
What are the components of the head of the sperm
Nucleus
Acrosome = thick cap, contains enzymes (hyaluronidase, proteolytic enzymes)
What are the components of the tail/flagellum of the sperm?
Axoneme = central skeleton of microtubules
Mitochondria
Dynein = ATPase
Sperm live best in a slightly _____ environment
Increased temperature _______ the lifespan of sperm, hence the role of the scrotum
Alkaline
Decreases
Lifespan of sperm in testes vs. in female genital tract
In testes = 1 month or greater
In female genital tract = 1-2 days
What is the role of testosterone in spermatogenesis? What hormone is required for stimulating adequate testosterone secretion?
Growth and division of spermatogonia; LH stimuates testosterone
What role does FSH play in spermatogenesis?
FSH stimulates sertoli cells
What role does growth hormone play in spermatogenesis?
Early division of spermatogonia
What route do sperm take prior to ejaculation?
Seminiferous tubules in testes —> epididymis —> vas deferens —> seminal vesicles and ejaculatory duct of prostate —> urethra via bulbourethral glands
Where are sperm stored in order to mature and gain coordinated motility, as well as undergo decapacitation?
Epididymis
________ = addition of molecules to the membranes to prevent premature acrosomal reaction; occurs in epidydimis
Decapacitation
The vas deferens functions to store sperm in the ______, as well as secretes fluid rich in ____ and _____ to nourish sperm prior to ejaculation
Ampulla; citrate; fructose
The ________ secrete fluid containing fructose, citrate, prostaglandins, and fibrinogen to nourish sperm.
What role do these prostaglandins play in fertilization?
Seminal vesicles
Prostaglandins thin out cervical mucous as well as cause reverse peristalsis in uterus so that sperm can make it to ovaries
The 2 ejaculatory ducts empty sperm into the ______, where they are stored as ____ until ejaculation
Prostatic urethra; semen
The prostate gland secretes slightly _____ fluid containing citrate, phosphate, calcium, and enzymes. This neutralizes the acidity of other seminal fluids, improves ______ of sperm, and aids in fertilization
Alkaline; motility
The ______ glands secrete clear fluid for lubrication of the urethra prior to ejaculation
Bulbourethral
What characteristics of semen are examined during lab testing?
Morphology Motility Total sperm count Vitality Volume
During arousal, sensory nerve signals at the glans penis are transmitted via _____ nerve to the sacral spinal cord
Pudendal
There are 3 total erectile bodis in the penis: 2 ______ and 1 _______
Corpora cavernosa; corpus spongiosum
During an erection, ________ tone predominates, with _____, _____, and/or _____ NTs participating
Parasympathetic; ACh; nitric oxide (NO); VIP
What role does nitric oxide play during an erection?
NO activates cGMP —> smooth muscle relaxation
Arterial dilation for increased blood flow; increased intercavernosal pressure for cavernosal expansion; veins compressed by engorged tissue leading to reduced venous drainage overall
What are some causes of erectile dysfunction?
Vascular disease (HTN, DM, atherosclerosis)
Neurogenic
Psychogenic
Endocrinologic
Medication-induced
Tx for erectile dysfunction
Phosphodiesterase-5 (PDE-5) inhibitors like viagra, which increase cGMP levels in erectile tissue
_______ = movement of semen toward ejaculatory ducts, which is under _____ nervous control
Emission; sympathetic
Emission consists of sequential peristaltic contractions of ________ smooth muscle, causing semen to move into internal urethra, and the ______ sphincter of the bladder closes
Vas deferens; internal
Ejaculation occurs when there is rhythmic contraction of the _____ and _____ muscles around the base of the penis, increasing the pressure in genital ducts and urethra
Bulbospongiosus; ischiocavernosus
________ occurs when mature sperm come in contact with fluids in the female tract
Capacitation
Capacitation involves loss of ________ factors in seminal fluid, loss of _______ on acrosome, which weakens the head of the sperm. There is also increased _____ permeability which leads to improved motility and changes in the cellular membrane allowing for acrosome to release enzymes. The ______ ______ receptors are exposed.
Inhibitory; cholesterol; calcium; zona pellucida
When the sperm and oocyte meet, the ______ membrane dissolves and enzymes escape. Among these enzymes:
______ breaks down the granuloma cell layer surrounding the ovum
Proteolytic enzymes breakdown tissue cells adhering to ovum, creating a pathway for sperm to pass through _______ and enter ovum so that the cell membranes can fuse and genetic material combines
Acrosomal
Hyaluronidase
Zona pellucida
