Chapter 10 - Reproductive Physiology Flashcards
Things that can define sex
Chromosomal Sex, Gonadal Sex, Phenotypic Sex, and Gender Identity
Chromosomal Sex - presence of Y chromosome is considered male, absence of Y chromosome is considered female
Gonadal Sex - presence of ovaries is designated female, presence of testes is designated male
Phenotypic Sex - appearance of external genitalia (most commonly used for definition of sex), newborn with penis is considered boy newborn with vagina is considered girl (this is typically consistent with gonadal sex in normal sexual differentiation AKA vagina + ovaries and penis + testes)
Gender identity - basic sense of being male or female, independent of any other definition of sex, regulated by brain development
Complete Androgen Insensitivity Syndrome (CAIS)
CAIS patients do not have androgen receptors for cells to respond to the male reproductive hormone (testosterone) released by the testes - exhibit male gonadal sex (have testes) but female phenotypic sex (have a vagina)
General Principle of Fetal Sexual Differentiation
Sex-determining region of the Y chromosome (SRY) gene directs the differentiation of fetal undifferentiated gonads into testes (it encodes the transcription factor that is necessary for development of testes)
In absence of SRY gene, the default for fetal sexual differentiation is female
In addition to SRY gene, sex hormones and receptors are necessary for the profession of male sexual differentiation from testes to male genitalia (genetic deficiencies in sex hormone-regulating enzymes (such as 5-alpha-reductase) and sex hormone receptors (such as androgen receptors) can result in abnormal male phenotypic sex despite normal male chromosomal sex)
Klinefelter and Turner Syndromes
Klinefelter - XXY individuals, develop as males because of presence of SRY gene
Turner - XO individuals, develop as female because no SRY gene
Male Fetal Sexual Differentiation
In fetuses with XY chromosomes, SRY gene enables undifferentiated gonads to develop into testes
Two hormones produced by fetal testes (anti-Mullerian hormone, AMH, and testosterone) are essential for development of male genitalia - AMH causes the regression of the Mullerian ducts in the male fetus and testosterone (produced by Leydig cells in the testes) enables development of Wolffian ducts into vas deferens, epididymis, and seminal vesicles
Female Exposure to Testosterone
Exposure of females to testosterone in utero can lead to abnormal differentiation toward the male phenotype
Female Fetal Sexual Differentiation
Absence of Y chromosome (and SRY gene) leads to female differentiation - undifferentiated gonads become ovaries
In the absence of testosterone, the Wolffian duct system regresses and Mullein duct system develops into the oviduct (fallopian tubule) and uterus and in the absence of DHT the external genitalia develop into a vagina
Meiosis
The basic cellular process for production of sperms in males and ova in females - begins with DNA replication (forming two sister chromatids per chromosome), during interphase prior to meiosis I, crossover between homologous chromosomes can lead to formation of recombinant chromatids from the two parent chromosomes (this is important for creating genetic diversity of sperms and eggs)
During human meiosis I, homologous chromosomes segregate from each other to form two daughter cells having 23 chromosomes, with two chromatids per chromosome
During human meiosis II, the two chromatids of each chromosome separate from each other to form two daughter cells each having 23 chromosomes with one chromatid per chromosome
Spermatogenesis by Meiosis
Start with a primary spermatocyte that has 23 pairs of homologous chromosomes with two chromatids per chromosome (before meiosis I is interphase and there is crossover between homologous chromosomes)
Then form two secondary spermatocytes after Meiosis I, each contains 23 chromosomes with two chromatids per chromosome
Then form four spermatids after Meiosis II, each contains 23 chromosomes with one chromatid per chromosome
Then differentiate into fully differentiated spermatozoa
Primary Spermatocyte (46 Chromosomes, 2 chromatids) –> Secondary Spermatocyte (23 chromosomes, 2 chromatids) –> Spermatid (23 chromosomes, 1 chromatid) –> Spermatozoa
Male Reproductive System Anatomy
Consists of penis, accessory glands (seminal vesicles, prostate gland), a pair of vas deferens, and two testes (organs of spermatogenesis)
The descent of testes out of the abdominal cavity through the inguinal canal during fetal development is essential for male fertility because spermatogenesis requires a temperature that is 2-4 degrees below core body temperature
Seminiferous tubules produce sperm, epididymus stores sperm, and vas deferens transports sperm to the penis
Spermatogenesis
Undifferentiated spermatogonium are nurtured to the differentiated spermatozoa by Sertoli cells in the seminiferous tubules of testes
The blood-testes barrier separates the Sertoli cell-formed seminiferous epithelium into the outer basal and inner adluminal compartments - the outer basal compartment is the location of spermatogonial renewal and differentiation and the inner adluminal compartment is the location of the production of secondary spermatocytes from primary spermatocytes by meiosis I and II and differentiation of spermatocytes into spermatid
The blood-testis berries is dynamic and allows for crossing of spermatocytes from the basal compartment to the adluminal compartment
A fully differentiated sperm has a head, mid-piece, tail and end piece:
The head holds the nucleus and acrosome, nucleus holds genetic material and acrosome contains enzymes that facilitate that entry of a sperm into the ovum during fertilization
Mid piece contains mitochondria for energy metabolism
Tail contains motor proteins for sperm motility
Semen ejaculated during intercourse is usually 10% sperm and 90% seminal plasma (secretions from seminal vesicles and prostate glands)
Male Reproductive Hormonal System
2 distinct branches: regulation of spermatogenesis and secretion of testosterone
Hypothalamus secretes GnRH which stimulates anterior pituitary to release FSH and LH
FSH stimulates spermatogenesis as nurtured by Sertoli cells in the testes and by negative feedback to the anterior pituitary, Sertoli cells secreting an inhibitory peptide inhibin which inhibits FSH secretion from anterior pituitary (negative feedback)
LH stimulates the secretion of testosterone by Leydig cells in the testis and testosterone inhibits the secretion of GnRH (at the hypothalamus) and LH (at the anterior pituitary) via negative feedback
Effects of Testosterone
- Maintenance of accessory reproductive organs
- Maintenance of secondary sex characteristics (growth of testes and penis)
- Increase sex drive
- Increase protein synthesis is skeletal muscle
- Bone growth in adolescence
5-alpha-reductase
5-alpha-reductase catalyzes the conversion of testosterone to DHT, a hormone necessary for the development of the penis
If males are exposed to 5-alpha-reductase inhibitors in utero it can lead to underdevelopment of the penis
Testosterone –> DHT happens in many organs (prostate, testis, hair follicles, liver, skin, brain) and in adults it is the major androgen in the prostate gland, excessive amounts can cause prostate enlargement and obstruction of urinary tract, treated with pharmacological inhibitors of 5-alpha-reductase
Erectile Function Basics
Penile erection is a complex spinal reflect that can be initiated by mechanical, visual and mental stimuli - erectile tissue is the vascular tissue (known as corpora cavernosa) that consists of vascular sinusoids lined with endothelial and vascular smooth muscle cells, when the corpora cavernosa is filled with blood, the penis becomes erect
Synthesis of NO in Penis
Nitric Oxide (NO) released by neurons (nonadrenergic and noncholenergic) and endothelial cells and prostaglandin E1 released by cells within the penis are the major mediators of cavernosal smooth muscle relaxation during penile erection, NO is synthesized from L-arginine by neuronal nitric oxide synthase in neurons and endothelial NO synthase in endothelial cells - both syntheses are stimulated by intracellular calcium concentration
Increase in intracellular [Ca2+] –> Activation of nNOS or eNOS –> Synthesis of NO from L-arginine
Vascular Steps for Penile Erection
- Dilation of cavernosal arterioles and arteries increases inflow of blood to corpora cavernosa
- Relaxation of cavernosal smooth muscle cells increases compliance of corporal cavernosa for filling of blood (corporal tissue swells with blood, erecting penis)
- Compression of cavernosal veins by the erectile tissue reduces the outflow of blood from corpora cavernosa and maintains the rigidity of the penis
Cascade to Penile Erection
- Electrical stimulation leads to increase in intracellular [Ca2+] in nonadrenergic, noncholinergic neurons and parasympathetic stimulation via muscarinic ACh receptors lead to increase in intracellular [Ca2+] in endothelial cells
- lipid soluble NO diffuses into cavernosal smooth muscle cells to induce muscle relaxation via
- NO activates guanylyl cyclase
- Guanylyl cyclase catalyzes the formation of cGMP from GTP (PDE5 catalyzes the degradation of cGMP to CMP so the guanylyl cyclase to PDE5 ratio is a major determinant of [cGMP] and strength of penile erection)
- cGMP activates cGMP-dependent protein kinase (cGK)
- cGK stimulates Ca2+ uptake by the SR, inhibits calcium channels and activates potassium channels on the cell membrane
- Decrease in intracellular [Ca2+] in cavernosal muscle cells
- Relaxation of cavernosal smooth muscle cells
- Penile erection
cGMP is the intracellular messenger for penile erection
Erectile Dysfunction
Inhibitors of PDE5 can treat erectile dysfunction by enhancing intracellular [cGMP] in cavernosal smooth muscle cells
PGE1 injection and pharmacological inhibitors of PDE2,3,4 have also been developed for treating erectile dysfunction
Prostaglandin E1 (PGE1)
Mediator of penile erection - PGE1 is released by cells in the penis and induces cavernosal smooth muscle relaxation by activating a GCPR on the cell membrane and triggering this cascade:
- Activation of adenylyl cyclase
- Conversion of ATP to cAMP (cAMP is degraded to AMP by PDE 2,3,4)
- Activation of cAMP-dependent protein kinase (PKA)
- PKA-mediated stimulation of Ca2+ uptake from SR, inhibition of calcium channels, and activation of K+ channels on cell membrane
- Decrease in intracellular [Ca2+]
- Cavernosal smooth muscle contraction
- Penile erection
Female Reproductive Anatomy
Consists of clitoris, labium minus and labium magus, vagina, cervix, uterus, uterine (fallopian) tubes, and ovaries
The clitoris, the main organ of orgasm in females, is similar to the penis in being developed from the same embryonic structure and having cavernous erectile tissue
The vagina is the entrance and exit from the female reproductive tract and vaginal mucosa is responsive to female reproductive hormones and undergoes changes in thickness during a menstrual cycle (in non-pregnant females it reaches its peak thickness at the middle of the cycle)
The uterus is the site of embryo implantation and placental formation as well as fetal development
Uterine (fallopian) tubes are conduits for the transport of ova from ovaries toward the uterus for fertilization with a sperm, which typically occurs inside the fallopian tube