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Reproductive Physiology
overview of 3 lectures from Prof. Pavalko
114
Physiology
Professional
04/06/2011

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Term
levels of sexual differentiation
Definition
establishment of genetic sex, differentiation of gonads, differentiation of internal reproductive structures, differentiation of external genitalia, gender role, and gender identity
Term
role of testosterone in differentiating internal ducts
Definition
Wolffian duct regresses in its absence and proliferates in its presence, fetus becomes male
Term
SRY
Definition
sex-determining gene on the Y chromosome, master switch of sex determination, encodes high mobility group (HMG) transcription factors, also called testis determining factor
Term
Swyer syndrome
Definition
pure gonadal dysgenesis, karyotype is XY, individual develops as female externally, no puberty, gonads typically removed due to predisposition of tumor development, treatment is estrogen/progesterone therapy
Term
XX male syndrome
Definition
translocation of SRY region of Y chromosome to X chromosome causes it
Term
Klinefelter's syndrome
Definition
one of most common sex chromosome disorders, XXY karyotype, inhibition of testicular development, reduced fertility, poor facial/chest hair growth, breast development, wide hips, pubic hair pattern is more female, individuals tend to have developmental or behavioral problems
Term
DHT
Definition
absolutely essential at normal levels to differentiate male genitalia
Term
5 alpha reductase
Definition
converts testosterone to DHT
Term
gender role
Definition
gender presented by individual to society, can be completely independent of genetic/anatomical sex, includes traits such as: name, dress, physical appearance, family role, occupation, and behavior
Term
gender identity
Definition
internal conviction of one's gender, inner sense of "male- or femaleness," poorly understood, argument of nature vs. nurture
Term
HPG axis
Definition
sequence of hormonal regulatory elements involving hypothalamus, anterior pituitary, and gonads, involves higher brain centers
Term
hypothalamus' role in HPG axis
Definition
releases gonadotropin releasing hormone
Term
anterior pituitary's role in HPG axis
Definition
GnRH released from hypothalamus triggers LH and FSH release
Term
gonadal role in HPG axis
Definition
secrete sex steroids and peptide hormones, act as site of germ cell production and maturation
Term
negative feedback from Sertoli cells
Definition
make inhibin when sperm count gets high, acts on anterior pituitary
Term
negative feedback from Leydig cells
Definition
testosterone (triggers spermatogenesis) acts on anterior pituitary and hypothalamus
Term
ovarian feedback on HPG axis
Definition
estrogen and progesterone exert negative influence during luteal phase on anterior pituitary and hypothalamus and positive influence on both during follicular phase
Term
higher center input on HPG axis
Definition
neurons controlling GnRH secretion receive stimuli from stress, emotion, visual/olfactory input
Term
neurotransmitters affecting HPG axis
Definition
norepinephrine, epinephrine, dopamine, acetylcholine, endorphins/opioids, neuropeptide Y, leptin, serotonin, cholecystokinin, and GABA (major inhibitory one)
Term
GnRH
Definition
neurons producing it are found in arcuate nucleus of mesiobasal hypothalamus, stored in granules, secreted in pulses every 70-90 minutes, has very brief half-life
Term
FSH and LH
Definition
produced by anterior pituitary, have identical alpha subunit and unique beta subunits, regulated by hypothalamic GnRH and feedback from gonadal hormones
Term
puberty
Definition
exact trigger unknown, influenced by: genetics, nutrition, weight, skeletal maturation, altitude, psychosocial/environmental factors; occurs when HPG axis matures
Term
mini-puberty in males
Definition
re-activation of HPG axis in first few months of life, testosterone levels equal those of adult, no physical consequence, function unknown
Term
changes at puberty of HPG axis
Definition
decreased sensitivity to negative feedback, increased pulsatile GnRH secretion, increased sensitivity of pituitary gonadotrophs, increased LH/FSH secretion, increased responsiveness of gonads, increased gonadal steroid production
Term
kisspeptin
Definition
stimulates release of hypothalamic GnRH, ligand of GPR54
Term
GPR54
Definition
7 transmembrane domain receptor, mutations in it cause hypogonadotropic hypogonadism, expressed by GnRH neurons
Term
adrenarche
Definition
onset of adrenal androgen production, occurs 2-3 years prior to puberty at ages 7-8, INDEPENDENT of gonadal production of sex steroids
Term
thelarche
Definition
onset of breast bud development, estrogen-induced, average onset 10.8 years in US
Term
pubarche
Definition
onset of pubic hair growth, influenced by estrogen or testosterone, 11 in females, 11.6 in males
Term
gonadarche
Definition
rise in gonadal sex steroids as result of HPG axis activation
Term
effects of sex steroids
Definition
growth acceleration, skeletal maturation, genital changes
Term
menarche
Definition
2-2.5 years after onset of puberty, 1st menses
Term
puberty in boys
Definition
age is 9-14, first sign is testicular enlargement, peak of growth is 2 years after girls
Term
precocious puberty
Definition
secondary sexual development before 7.5 in girls and 9 in boys, categories are: normal variants, central, and peripheral
Term
central precocious puberty
Definition
majority of cases of abnormal development, same physiology as normal route but earlier, more common in girls, any form of CNS insult increases risk, gradual secondary sexual development, potentially compromises adult height
Term
pseudoprecocious puberty
Definition
high levels of sex hormones are produced, cause may be tumor in adrenal gland or ovary/testis, sex glands do not mature but child appears adult-like
Term
peripheral precocious puberty
Definition
abnormal source of sex steroids, rare, source of steroids endogenous or exogenous, often has acute onset
Term
McCune-Albright syndrome
Definition
caused by activating mutation in G-protein signaling, elevated cAMP in endocrine tissue, triad of precocious puberty/cafe-au-lait birthmarks/fibrous bone dysplasia, causes ovarian cysts in girls, somatic mutation in a mosaic distribution
Term
delayed puberty
Definition
failure of onset by 13 in girls or 14 in boys, can be normal genetic variant or pathological (anywhere in HPG axis)
Term
characteristics of testes
Definition
dual function (spermatogenesis and steroidogenesis), is site of sperm and testosterone production, comprised of germ cells/Sertoli cells/Leydig cells
Term
blood-testis barrier
Definition
created by tight junctions between Sertoli cells, prevents immune attack on spermatocytes
Term
Sertoli supportive functions
Definition
support gametes, phagocytose damaged cells, assist spermiation by proteolytic action of plasmin, synthesize transferrin
Term
Sertoli cell secretory functions
Definition
contain FSH receptors (linked to G-protein), produce androgen binding protein/inhibin/plasminogen activator
Term
inhibin in males
Definition
made by Sertoli cells, negative feedback for FSH, has paracrine actions
Term
Leydig cell actions
Definition
contain LH receptors, stimulate steroidogenesis, produce testosterone
Term
Sertoli-Leydig interactions
Definition
testosterone diffuses from Leydig to Sertoli cells, Sertoli cells aromatize testosterone to estradiol, estradiol diffuses back to Leydig cells
Term
testes also produce:
Definition
opioids, AVP, oxytocin, GnRH-like peptide, growth factors, and neurotransmitters
Term
spermatogenesis
Definition
3 distinct phases: mitosis, meiosis, spermiogenesis; 200 million/day, takes 60-70 days, "wave" ensures uninterrupted supply of sperm
Term
spermiogenesis
Definition
differentiation of spermatid to spermatozoa, "axoneme" formed, "acrosome" covers nucleus
Term
spermatozoa
Definition
made of head, middle piece (energy supply), tail (microtubules surrounded by fibrous sheath)
Term
testosterone in spermiogenesis
Definition
allows capacitation in the epididymis
Term
seminal fluid
Definition
2-5 mL, 10% sperm by volume, secretions from accessory glands, made up of fructose, ascorbic acid, prostaglandins, and fibrinolysin
Term
expulsion of semen
Definition
occurs in 2 phases: emission (movement into urethra by lumbar spinal nerves and smooth muscles) and ejaculation (spinal reflex mechanism)
Term
testicular steroidogenesis
Definition
pathway exists in multiple tissues, relative products depend on which enzymes are predominant, pregnenolone is key intermediate
Term
LH receptor
Definition
stimulates testosterone synthesis via G-protein mediated cAMP formation w/ activation of PKA, has high affinity on Leydig cell
Term
"testotoxicosis"
Definition
familial male limited precocious puberty at 2-6 years, caused by heterozygous missense mutation in LH receptor, treated w/ androgen receptor blocker and aromatase inhibitor
Term
metabolism of testosterone
Definition
immediately diffuses into blood after formation, majority circulates in bound form, most converted to DHT or estradiol
Term
DHT
Definition
metabolized from testosterone by 5-alpha reductase (which is also active in hair follicles/sebaceous glands), 2-3x more potent, critical for normal differentiation
Term
estradiol in males
Definition
aromatization occurs in many tissues (including brain), levels approach those in women during follicular phase, abnormal ratio compared to T causes gynecomastia
Term
androgen actions
Definition
responsible for: sexual differentiation, secondary characteristic development, mediation of hair growth and balding, lipid levels, RBC mass, and masculinization of the brain
Term
androgen effects on brain
Definition
controls hierarchy, mating/copulatory behaviors; no correlation between hormone levels and libido
Term
disorders of male reproduction
Definition
50% of infertility due to endocrine disorders, Kallmann syndrome, primary hypogonadism, and other endocrinopathy
Term
Kallmann syndrome
Definition
caused by mutations within KAL gene, results in hypogonadotropic hypogonadism and anosmia (due to failure of migration of GnRH-secreting neurons from olfactory placode to hypothalamus)
Term
hypothalamic-pituitary-ovarian axis
Definition
axis in females, hormone secretion is cyclic and highly synchronized, steroidal feedback is both positive and negative
Term
ovaries
Definition
site of germ cell maturation and steroidogenesis in females, produces estrogen/progesterone/inhibin
Term
reproductive ducts in females
Definition
responsible for transportation of ova and maintenance of conceptus during pregnancy
Term
estrogen production site
Definition
follicular cells
Term
progesterone production site
Definition
corpus luteum
Term
folliculogenesis
Definition
progression from primordial follicle to mature follicle
Term
FSH role in folliculogenesis
Definition
stimulates granulosa cell estradiol production, granulosa cell mitosis (and in turn enhancement of positive feedback), and hormone itself is important constituent of liquor folliculi
Term
gonadotropin dependence of follicles
Definition
during primordial stage: independent, beyond primary stage: dependent
Term
ovarian steroidogenesis
Definition
requires coordination between granulosa and theca cells and LH/FSH, primary product is estradiol from precursors
Term
granulosa cell characteristics
Definition
only cell type containing FSH receptors in female, depends on androgens from theca cells, has LH receptors in mature follicle
Term
theca cell characteristics
Definition
cell containing LH receptors, have access to circulating cholesterol, produce androgens
Term
LH surge effects on dominant follicle
Definition
this hormone triggers resumption of meiosis (which inhibits oocyte maturation factor), increases blood flow, activates proteolytic enzymes, shifts steroidogenesis towards progesterone, causes follicular rupture 30-36 hours after onset
Term
events prior to ovulation
Definition
basement membrane disintegrates, granulosa cells undergo luteinization (become vascular and lipid rich), plasmin degrades follicular wall
Term
menstrual cycle
Definition
results from steroid withdrawal from corpus luteum regression, has follicular/luteal/menses phases
Term
menses stage
Definition
at this point, steroid hormones drop and FSH levels rise
Term
follicular phase
Definition
at this point estradiol levels increase and peak on day 12, estradiol exhibits positive feedback on LH release
Term
luteal phase
Definition
at this point, steroid levels are rising due to corpus luteum; begin to fall when CL fails, which triggers next stage and repeat of cycle
Term
proliferative stage
Definition
occurs at same time as follicular phase in ovary, endometrium hypertrophies, spiral arteries form
Term
secretory phase
Definition
begins in uterus at ovulation, uterine glands coil/secrete mucus, arteries become tortuous
Term
ischemic stage
Definition
occurs when corpus luteum fails, results in necrosis of uterine mucosa, blood supply decreases, prostaglandins are released
Term
menstrual stage
Definition
occurs in uterus, desquamation of functional layer of endometrium
Term
menopause
Definition
in humans only, happens when oocyte supply is exhausted, gonadotropins increase, stromal cells continue to produce androstenedione, decreased estrogen results in: hot flashes, decreased bone mass, increased cardiovascular risk, and atrophy of vaginal epithelium
Term
major abnormalities of female reproduction
Definition
primary and secondary amenorrhea, infertility
Term
severe primary hypothyroidism in children
Definition
causes precocious puberty, due to cross-reactivity of TSH at FSH receptor, remits with proper treatment of primary problem
Term
primary amenorrhea
Definition
failure of menses to occur at 16; can be result of decreased/inhibited GnRH secretion (affects pulsatile release of LH/FSH), gonadal dysgenesis (streak gonads in Turner syndrome), or disorder of sex development
Term
Turner syndrome
Definition
rate of 1:2500, missing or structurally abnormal X chromosome, characteristics are: short stature, accelerated ovarian atresia, delayed puberty/primary amenorrhea
Term
secondary amenorrhea
Definition
happens after menses already start, temporary absence; caused by pregnancy, endocrine disorders (hypo/hyperthyroidism, hyperprolactinemia, non-classic CAH), polycystic ovarian syndrome, or anorexia
Term
polycystic ovary syndrome
Definition
most common reproductive abnormality in women, increased androgen production but no ovulation, obesity and hirsutism are common features, unifying feature is insulin resistance
Term
fertilization
Definition
requires rapid transport of both germ cells, facilitated by female reproductive tract, head adheres to zona pellucida through ZP3, acrosome reaction is triggered (dissolves cumulus and penetrates ZP), sperm crosses perivitelline space, adheres to oolemma, head/tail engulfed
Term
implantation of blastocyst
Definition
occurs in uterus 7 days after fertilization, proteases from trophoblast cells mediate endometrial invasion, conversion of trophoblasts takes place, dilation of endometrial blood vessels, lacunae appear, villi from embryo establish functional communication between vascular systems
Term
fertilization events following sperm penetration
Definition
cortical granules are released and fuse w/ oolema over entire surface, zona reaction prevents polyspermy, intracellular Ca2+ increase triggers 2nd meiotic division, pronuclei fuse and form zygote
Term
blastocyst
Definition
20-30 cell stage of embryo, fluid-filled cavity with trophoblast (embryonic part of placenta) and inner embryoblast (fetus), will attach to uterine wall
Term
decidua
Definition
product of transformation of endometrium occurring at implantation, requires progesterone from CL
Term
endometriosis
Definition
condition in which cells proliferate inappropriately, hormonally influenced, main symptom is pelvic pain, is a common cause of infertility
Term
placental structure
Definition
maternal and fetal components interdigitate, hemochoroidal (maternal blood bathes endothelium and connective tissue)
Term
amnion
Definition
encloses fetus, thin avascular membrane w/ amniotic fluid
Term
chorion
Definition
adjacent layer to amnion, encloses fetus
Term
placental function
Definition
delivery of nutrients/oxygen/carbon dioxide, removal of waste, pinocytosis/diffusion of glucose/AAs/electrolytes/hormones
Term
placenta as endocrine organ
Definition
produces progesterone, estrogen, human chorionic gonadotropin, human placental lactogen, and other peptides
Term
human chorionic gonadotropin
Definition
trophoblast cells of embryonic placenta produce it, extends life of corpus luteum, first sign of pregnancy 7-10 days post-fertilization, is a glycoprotein comprised of alpha and beta subunits, structurally similar to LH, stimulates progesterone production by CL, may have critical role throughout pregnancy
Term
human placental lactogen
Definition
has lactogenic and growth hormone-like actions, secreted by suncytiotrophoblasts, main function is to alter fuel availability (antagonizes maternal glucose consumption, mobilizes fat stores), ensures fetal nutrition
Term
progesterone during pregnancy
Definition
essential hormone for pregnancy maintenance, placenta produces it by around 8 weeks, rises throughout pregnancy, maternal LDL cholesterol is substrate (trophoblast cells have receptors for LDL), prevents uterine contractions, inhibits prostaglandin formation, inhibits T-cell immune response to pregnant uterus
Term
estrogen during pregnancy
Definition
estradiol and estriol are major hormones produced, rise throughout pregnancy, production requires fetoplacental unit, involved in implantation, increases uterine size and blood flow, assists fetal organ development
Term
estrogen effect on pregnant woman
Definition
increases breast and adipose tissue, causes peripheral vasodilation (sinus congestion/bleeding gums/sensation of warmth), increases blood volume/heart rate/cardiac output/uterine blood flow
Term
progesterone effect on pregnant woman
Definition
allows smooth muscle relaxation (increased GERD and constipation), decreases contractions, increases minute ventilation
Term
parturition
Definition
birth process, has hormonal/mechanical/maternal/fetal factors involved, estrogen activates events while progesterone inhibits it, paracrine factors may be most important
Term
sequence of parturition
Definition
sharp decrease in progesterone prior to labor, amniotic fluid prostaglandin concentration increases at onset (stimulates contractions and cervical ripening), oxytocin augments labor by increasing uterine responsiveness, fetal cortisol rises, vaginal/cervical dilation cause explosive pulsatile oxytocin release ("Fergusson reflex")
Term
twinning
Definition
occurs in 3% of live births, approximately 2/3rds are fraternal, division of zygote at day 13 causes conjoining, incidence of dizygotics affected by: assisted reproduction, ethnicity, maternal age and other characteristics
Term
contraception by preventing germ cell contact
Definition
includes coitus interruptus, rhythm method, barrier methods (condoms, etc.)
Term
contraception by preventing ovulation
Definition
inhibition of LH and FSH through negative feedback, also adversely affects environment of reproductive tract, includes emergency methods w/ high doses of progestin, IUDs, etc.
Term
lactation
Definition
production of milk, controlled primarily by pituitary hormones, requires suckling to continue, major source of nutrition for newborns
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