Reproduction Flashcards
Sonic Hedgehog Gene
Produced at base of limbs in zone of polarizing activity
Involved in patterning along anterior-posterior axis.
Involved in CNS development; mutation can cause holoprosencephaly
Wnt-7 gene
Produced at apical ectodermal ridge (thickened ectoderm at distal end of each developing limb)
Necessary for proper organization along dorsal-ventral axis
FGF gene
Produced at apical ectodermal ridge (like Wnt-7).
Stimulates mitosis of underlying mesoderm, providing for lengthening of limbs
Homeobox (Hox) genes
Involved in segmental organization of embryo in a craniocaudal direction.
Code for transcription factors.
Hox mutations lead to appendages in wrong locations
Early Fetal development (through week 10)
Day 0 - Fertilization by sperm, forming zygote, initiating embryogenesis.
Within week 1 - hCG secretion begins around the time of implantation of blastocyst (it “sticks” at day 6)
Within week 2 - Bilaminar disc (epiblast, hypoblast). 2 weeks = 2 layers
Within week 3 - Trilaminiar disc. Gastrulation. Primitive streak, notochord, mesoderm and its organization, and neural plate begin to form.
Weeks 3-8 (Embryonic period) - Neural tube formed by neuroectoderm and closes by week 4. Organogenesis. Extremely susceptible to teratogens
Week 4 - Heart begins to beat. Upper and lower limb buds begin to form. 4 weeks = 4 limbs.
Week 6 - Fetal cardiac activity visible by transvaginal US
Week 10 - Genitalia have male/female characteristics
Gastrulation
Within week 3
Process that forms the trilaminar embryonic disc. Establishes the ectoderm, mesoderm, and endoderm germ layers.
Starts with epiblast invaginating to form the primitive streak.
Ectoderm
External/outer layer
1) Surface Ectoderm - Epidermis; adenohypophysis (from Rathke pouch); lens of eye; epithelial linings of oral cavity, sensory organs of ear, and olfactor epithelium; epidermis; anal canal below the pectinate line; parotid, sweat, and mammary glands
Craniopharyngioma - benign Rathke pouch tumor with cholesterol crystals, calcifications
2) Neuroectoderm - Brain (neurohypophysis, CNS, neurons, oligodendrocytes, astrocytes, ependymal cells, pineal gland), retina and optic nerve, spinal cord
3) Neural crest - PNS (dorsal root ganglia, cranial nerves, celiac ganglion, Schwann cells, ANS), melanocytes, chromaffin cells of adrenal medulla, parafollicular (C) cells of thyroid, pia, and arachnoid, bones of the skull, odontoblasts, aorticopulmonary septum
Mesoderm
Middle/”Meat” layer
Muscle, bone, connective tissue, serous linings of body cavities (peritoneum), spleen (derived from foregut mesentery), cardiovascular structures, lymphatics, blood, wall of gut tube, vagina, kidneys, adrenal cortex, dermis, testes, ovaries
Notochord induces ectoderm to form neuroectoderm (neural plate). Its only postnatal derivative is the nucleus pulposus of the intervertebral disc
Mesodermal defects = VACTERL
V = vertebral defects A = Anal atresia C = Cardiac defects T/E = Tracheo-Esophageal fistula R = Renal defects L = Limb defects (bone and muscle)
Endoderm
Gut tube epithelium (including anal canal above the pectinate line), most of urethra (derived from urogenital sinus), luminal epithelial derivatives (lungs, liver, gallbladder, pancreas, eustachian tube, thymus, parathyroid, thyroid follicular cells)
Organ morphogenesis errors
1) Agenesis - absent organ bc of absent primordial tissue
2) Aplasia - absent organ despite presence of primordial tissue
3) Hypoplasia - Incomplete organ development; primordial tissue present
4) Deformation - Extrinsic disruption; occurs after embryonic period
5) Disruption - Secondary breakdown of previously normal tissue or structure (e.g. amniotic band syndrome)
6) Malformation - Intrinsic disruption; occurs during embryonic period (wks 3-8)
7) Sequence - Abnormalities result from single primary embryologic event (e.g. oligohydramnios leading to Potter Sequence)
Teratogens
Most susceptible in wks 3-8 of pregnancy. Before week 3, “all or none” effects. After week 8, growth and function affected.
Medications that are teratogens
1) ACE Inhibitors - Renal damage
2) Alkylating agents - Absence of digits, multiple anomalies
3) Aminoglycosides - CN8 toxicity
4) Carbamazepine - Facial dysmorphism, developmental delay, neural tube defects, phalanx/fingernail hypoplasia
5) Diethylstilbestrol (DES) - Vaginal clear cell adenocarcinoma, congenital Mullerian anomalies
6) Folate antagonists - Neural tube defects
7) Isotretinoin - Multiple severe birth defects (contraception mandatory)
8) Lithium - Ebstein anomaly (atrialized RV)
9) Methimazole - Aplasia cutis congenita
10) Phenytoin - Fetal hydantoin syndrome - cleft palate, cardiac defects, phalanx/fingernail hypoplasia
11) Tetracyclines - Discolored teeth
12) Thalidomide - Limb defects (phocomelia, micromelia - flipper limbs)
13) Valproate - Inhibition of maternal folate absorption leads to neural tube defects
14) Warfarin - Bone deformities, fetal hemorrhage, abortion, ophthalmologic abnormalities (Use heparin - doesn’t cross placenta)
Substance abuse/teratogens
1) Alcohol - Common cause of birth defects and intellectual disability; fetal alcohol syndrome
2) Cocaine - Abnormal fetal growth and fetal addiction; placental abruption
3) Smoking (Nicotine, CO) - Low birth weight (leading cause in developed countries), preterm labor, placental problems, IUGR, ADHD - Nicotine leads to vasoconstriction. CO leads to impaired O2 delivery
Other teratogens
1) Iodine (lack or excess) - Congenital goiter or hypothyroidism (cretinism)
2) Maternal diabetes - Caudal regression syndrome (anal atresia to sirenomelia), congenital heart defects, neural tube defects
3) Vitamin A (excess) - Extremely high risk for spontaneous abortions and birth defects (cleft palate, cardiac)
4) X-Rays - Microcephaly, intellectual disability - minimized by lead shielding
Fetal Alcohol Syndrome
Leading cause of intellectual disability in the US.
Newborns of alcohol-consuming mothers have higher incidence of congenital abnormalities, including pre and postnatal developmental retardation, microcephaly, facial abnormalities (smooth philtrum, hypertelorism), limb dislocation, heart defects.
Heat-lung fistulas and holoprosencephaly in most severe form. Mechanism is failure of cell migration.
Placenta
Primary site of nutrient and gas exchange between mother and fetus
Fetal component
1) Cytotrophoblast - inner layer of chorionic villi. Cytotrophoblast makes Cells.
2) Syncytiotrophoblast - Outer layer of chorionic villi; secretes hCG (structurally similar to LH; stimulates corpus luteum to secrete progesterone during first trimester)
Lacks MHC-1 expression leading to lower chance of attack by maternal immune system
Maternal component
1) Decidua basalis - Derived from endometrium. Maternal blood in lacunae
Umbilical cord
Umbilical arteries (2) - return deoxygenated blood from fetal internal iliac arteries to placenta
Umbilical vein (1) - supplies oxygenated blood from placenta to fetus; drains into IVC via liver or via ductus venosus
Single umbilical artery (2 vessel cord) is associated with congenital and chromosomal abnormalities
Umbilical arteries and vein are derived from allantois
Urachus
In the 3rd week the yolk sac forms the allantois, which extends into urogenital sinus. Allantois becomes the urachus, a duct between fetal bladder and yolk sac.
Patent Urachus - total failure to obliterate leads to urine discharge from umbilicus
Urachal cyst - Partial failure of urachus to obliterate; fluid-filled cavity lined with uroepithelium, between umbilicus and bladder. Can lead to infection, adenocarcinoma
Vesicourachal diverticulum - Slight failure to obliterate leads to outpouching of bladder
Vitelline duct
7th week - obliteration of vitelline duct (omphalo-mesenteric duct), which connects yolk sac to midgut lumen
Vitelline fistula - vitelline duct fails to close leading to meconium discharge from umbilicus
Mechel diverticulum - partial closure of vitelline duct, with patent portion attached to ileum (true diverticulum). May have heterotopic gastric and/or pancreatic tissue causing melena, hematochezia, abdominal pain.
Aortic arch derivatives
Develop into arterial system
1) Part of maxillary artery (branch of external carotid)
2) Stapedial artery and hyoid artery (Second = Stapedial)
3) Common Carotid artery and proximal part of internal Carotid artery (C is 3rd letter)
4) On left, aortic arch; On right, proximal part of R Subclavian artery
6) Proximal part of pulmonary arteries and (on left only) ductus arteriosis)
Branchial apparatus
Also called pharyngeal apparatus. Composed of branchial clefts, arches, pouches
Brancial clefts = derived from ectoderm. Also called grooves
Arches = derived from mesoderm (muscles, arteries) and neural crest (bones, cartilage)
Pouches = derived from endoderm
Branchial cleft derivatives
1st cleft = external auditory meatus
2-4 = temporary cervical sinuses, which are obliterated by proliferation of 2nd arch mesenchyme
Persistent cervical sinus leads to branchial cleft cyst within lateral neck
1st Branchial Arch
Mechel cartilage: Mandible, Malleus, incus, spheno-Mandibular ligament
Muscles of Mastication (temporalis, Masseter, lateral, and Medial pterygoids), Mylohyoid, anterior belly of digastric, tensor tympani, tensor veli palatini
CN V2 and V3 (chew)
Treacher Collins Syndrome - 1st arch neural crest fails to migrate leading to mandibular hypoplasia, facial abnormalities
2nd Branchial Arch
Reichert cartilage: Stapes, Styloid process, lesser horn of hyoid, Stylohyoid ligament
Muscles of facial expression, Stapedius, Stylohyoid, platySma, posterior belly of digastric
CN VII (facial expression - smile)
Congenital Pharyngocutaneous fistula - persistence of cleft and pouch leads to fistula between tonsilar area and lateral neck
3rd Branchial Arch
Cartilage: greater horn of hyoid
Stylopharyngeous (think of styloPHARYNGEOUS innervated by glossoPHARNYGEAL nerve)
CN IX (stylopharyngeous swallows stylishly)
4th-6th Branchial Arches
Cartilage: thyroid, cricoid, arytenoids, corniculate, cuneiform
4th: most pharyngeal constrictors; cricothyroid, levator veli palatini
6th: All intrinsic muscles of larynx except cricothyroid
4th: CN X (superior laryngeal branch) - swallow
6th: CN X (recurrent laryngeal branch) - speak
Arches 3 and 4 form posterior 1/3 of tongue; arch 5 makes no major developmental contributions
1st Branchial pouch
Develops into middle ear cavity, eustachian tube, mastoid air cells
1st pouch contributes endoderm-lined structures to ear
2nd Branchial pouch
Develops into epithelial lining of palatine tonsil
3rd Branchial pouch
Dorsal wings - develop into inferior parathyroids
Ventral wings - develop into thymus
3rd pouch contributes to 3 structures (thymus, L and R inferior parathyroids)
3rd pouch structures end up below 4th pouch structures
4th Branchial pouch
Dorsal wings - develop into superior parathyroids
DiGeorge Syndrome
Aberrant development of 3rd and 4th pouches leads to T cell deficiency (thymic aplasia) and hypocalcemia (failure of parathyroid development)
Associated with cardiac defects (conotruncal anomalies)
MEN 2A
Mutation of germline RET (neural crest cells):
Adrenal medulla (pheochromocytoma)
Parathyroid (tumor): 3rd/4th pharyngeal pouch
Parafollicular cells (medullary thyroid cancer): derived from neural crest cells; associated with 4th/5th pharyngeal pouches
Cleft Lip and palate
Lip - failure of fusion of the maxillary and medial nasal processes (formation of primary palate)
Palate - failure of fusion of the 2 lateral palatine processes with the nasal septum and/or median palate process (formation of secondary palate)
Cleft lip and cleft palate have 2 distinct etiologies, but often occur together.
Genital embryology
1) Female - default development. Mesonephric duct degenerates and paramesonephric duct develops
2) Male - SRY gene on Y chromosome - produces testis-determining factor leading to testes development
- Sertoli cells secrete Mullerian inhibitory factor (MIF) that suppresses development of paramesonephric ducts.
- Leydig cells secrete androgens that stimulate development of mesonephric ducts
3) Paramesonephric (Mullerian) duct - Develops into female internal structures - fallopian tubes, uterus, upper portion of vagina (lower portion from urogenital sinus)
Mullerian agenesis - may present as primary amenorrhea (due to a lack of uterine development) in females with fully developed secondary sexual characteristics (functional ovaries)
4) Mesonephric (Wolffian) Duct - Develops into male internal structures (except prostate) - SEED - Seminal vesicles, Epididymis, Ejac duct, Ductus deferens.
In females, remnant of mesonephric duct becomes the Gartner duct
SRY Gene
1) No sertoli cells or lack of MIF leads to development of both male and female internal genitalia and male external genitalia
2) 5a-reductase deficiency - inability to convert testosterone into DHT leading to male internal genitalia, ambiguous external genitalia until puberty (when higher testosterone levels cause masculinization)
Uterine (Mullerian Duct) abnormalities
1) Septate uterus - common anomaly vs normal uterus. Incomplete resorption of septum. Lower fertility. Treat with septoplasty.
2) Bicornuate uterus - Incomplete fusion of Mullerian ducts. higher risk of complicated pregnancy
3) Uterus didelphys - Complete failure of fusion leads to double uterus, vagina, and cervix. Pregnancy possible
Male/female genital homologs
Estrogen takes things to their female form. Dihydrotestosterone takes things to their male form.
1) Glans Penis/Glans Clitoris = Genital tubercle
2) Corpus Cavernosum and spongiosum/Vestibular Bulbs = Gential tubercle
3) Bulbourethral glands (Cowper)/ Greater vestibular glands (Bartholin) = Urogenital sinus
4) Prostate gland/Urethral and paraurethral glands (Skene) = Urogenital sinus
5) Ventral shaft of penis (penile urethra)/Labia minora = Urogenital folds
6) Scrotum/Labia majora = Labioscrotal swelling
Congenital penile abnormalities
1) Hypospadias - abnormal opening of penile urethra on ventral surface of penis due to failure of urethral folds to fuse
Hypospadias is more common than epispadias. Associated with inguinal hernia and cryptorchidism
Hypo is below
2) Epispadias - Abnormal opening of penile urethra on dorsal surface of penis due to faulty positioning of genital tubercle
Exstrophy of the bladder is associated with Epispadias.
Descent of testes and ovaries
1) Gubernaculum (band of fibrous tissue)
Male remnant = Anchors testes within scrotum
Female remnant = Ovarian ligament + Round lig of uterus
2) Processus vaginalis (evagination of peritoneum)
Male remnant = Forms tunica vaginalis
Female remnant = Obliterated
Venous drainage of gonads
Left ovary/testes - left gonadal vein - left renal vein - IVC
Right ovary/testes - right gonadal vein - IVC
Left takes Longest way. Bc the left spermatic vein enters the left renal vein at a 90 degree angle, flow is less laminar on left than on the right. This leads to left venous pressure being higher than right venous pressure. Also, varicocele is more common on the LEFT.
Lymphatic drainage of gonads
Ovaries/testes - para-aortic lymph nodes.
Distal vagina/vulva/scrotum - superficial inguinal nodes
Proximal vagina/uterus - obturator, external iliac, and hypogastric nodes
Infundibulopelvic ligament
Contains ovarian vessels
Connects ovaries to lateral pelvic wall
Ligate these vessels during oophorectomy to avoid bleeding.
The URETER runs retroperitoneally, close to gonadal vessels. So the URETER is at risk of injury during ligation of uterine vessels
Cardinal ligament
Connects cervix to side wall of pelvis
Contains uterine vessels
URETER is at risk of injury during ligation of uterine vessels during hysterectomy
Round ligament of uterus
Connects uterine fundus to labia majora
Derivative of gubernaculum. Travels through round injuinal canal; above the artery of Sampson
Broad ligament
Connects uterus, fallopian tubes and ovaries to pelvic side wall
Contains ovaries, fallopian tubes, round ligaments of uterus
Mesosalpinx, mesometrium, and mesovarium comprise this ligament
Ovarian ligament
Connects medial pole of ovary to lateral uterus
Derivative of gubernaculum
Female repro epithelial histology
1) Vagina = Stratified squamous epithelium, nonkeratinized
2) Ectocervix = Stratified squamous epithelium, nonkeratinized
3) Transformation zone = Squamocolumnar junction (most common area for cervical cancer)
4) Endocervix = Simple columnar epithelium
5) Uterus = Simple columnar epithelium with long tubular glands in follicular phase; coiled glands in luteal phase
6) Fallopian tube = Simple columnar epithelium
7) Ovary, outer surface = Simple cuboidal epithelium (germinal epithelium covering surface of ovary)
Autonomic innervation of male sexual response
1) Erection - Parasympathetic (pelvic nerve)
NO leads to increased cGMP leading to smooth muscle relaxation leading to vasodilation - proerectile.
NE leads to increased intracellular Ca causing smooth muscle contraction leading to vasoconstriction - antierectile
2) Emission - Sympathetic (hypogastric nerve)
3) Ejaculation - visceral and somatic nerves (pudendal nerve)
PDE5 inhibitors (sildenafil) lower cGMP breakdown.
Urethral injury
Suspect if blood is seen at urethral meatus
Posterior urethra - membranous urethra prone to injury from pelvic fracture; bulbar urethra susceptible to blunt force. Injury can cause urine to leak into retropubic space
Anterior urethra - penile urethra at risk of damage due to perineal straddle injury. Can cause urine to leak beneath deep fascia of Buck. If fascia is torn, urine escapes into superficial perineal space.
What cells are within the seminiferous tubules?
Spermatogonia (germ cells)
Sertoli Cells (non-germ cells)
Leydig Cells (endocrine cells)
Spermatogonia (germ cells)
Maintain germ pool and produce primary spermatocytes
Line the seminiferous tubules
Sertoli cells
Non-germ cells
1) Secrete inhibin which inhibits FSH
2) Secrete androgen-binding protein. This maintains local levels of testosterone.
3) Tight junctions between adjacent Sertoli cells form blood-testis barrier. This isolates gametes from autoimmune attack.
4) Support and nourish developing spermatazoa
5) Regulates spermatogenesis
6) Produces MIF
7) Temperature sensitive - lower sperm production and lower inhibin when temperature is higher.
8) Lines seminiferous tubules
9) Converts testosterone and androtestosterone to estrogen via aromatase
Sertoli cells Support Sperm Synthesis
Homolog of female granulosa cells.
Estrogen
1) Source: Ovary (17B-estradiol), placenta (estriol), adipose tissue (estrone via aromatization)
2) Potency - estradiol > estrone > estriol
3) Function - Development of genitalia and breast, female fat distribution
Growth of follicle, endometrial proliferation, increased myometrial excitability
Upregulation of estrogen, LH, and progesterone receptors; feedback inhibition of FSH and LH, then LH surge; stimulation of prolactin secretion
Higher transport proteins, SHBG; Raises HDL; Lowers LDL
In pregnancy, there is a 50-fold increase in estradiol and estrone. 1000 fold increase in estriol (indicator of fetal well-being)
Estrogen receptors expressed in cytoplasm; translocate to nucleus when bound by estrogen.
Progesterone
1) Source: Corpus luteum, placenta, adrenal cortex, testes
2) Function: Stimulation of endometrial glandular secretions and spiral artery development.
Maintenance of pregnancy
Lowers myocardial excitability
Production of thick cervical mucus, which inhibits sperm entry into uterus
Increased body temp
Inhibition of gonadotropins (LH, FSH)
Uterine smooth muscle relaxation (preventing contractions)
Lowers estrogen receptor expression
Prevents endometrial hyperplasia
Fall in progesterone after delivery disinhibits prolactin leading to lactation. Increased progesterone is indicative of ovulation.
Tanner stages of development
Tanner stage is assigned independently to genitalia, pubic hair, and breast (You can have tanner stage 2 genitalia and stage 3 pubic hair)
I - Childhood (prepubertal)
II - Pubic hair appears (pubarche); breast buds (thelarche)
III - Pubic hair darkens and becomes curly; penis size/length increases; breasts enlarge
IV - Penis width increases, darker scrotal skin, development of glans; raised areolae
V - Adult; areolae are no longer raised
Menstrual cycle irregularities
Dysmenorrhea: Pain with menses; often associated with endometriosis
Oligomenorrhea: > 35 day cycle
Polymenorrhea: 80 mL blood loss or > 7 days of menses
Menometrorrhagia: Heavy, irregular menstruation
Oogenesis
Primary oocytes begin meiosis I during fetal life and complete meiosis I just prior to ovulation.
Meiosis I is arrested in prophase I for years until ovulation (primary oocytes)
Meiosis II is arrested in metaphase II until fertilization (secondary oocytes)
If fertilization does not occur within 1 day, the secondary oocyte degenerates
Ovulation
Increased estrogen, Increased GnRH receptors on anterior pituitary
Estrogen surge then stimulates LH release leading to ovulation (rupture of follicle)
Increased temperature (progesterone induced)
Mittelschmerz - transient mid-cycle ovulatory pain; classically associated with peritoneal irritation (follicular swelling/rupture, fallopian tube contraction). Can mimic appendicitis
Pregnancy
Fertilization most commonly occurs in upper end of fallopian tube (the ampulla). Occurs within 1 day of ovulation.
Implantation within the wall of the uterus occurs 6 days after fertilization. Syncytiotrophoblasts secrete hCG, which is detectable in blood 1 week after conception and on home test in urine 2 weeks after conception.
Lactation
After labor, the decrease in progesterone and estrogen disinhibits lactation. Suckling is required to maintain milk production, since increased nerve stimulation leads to higher oxytocin and prolactin.
Prolactin - induces and maintains lactation and lowers reproductive function
Oxytocin - assists in milk letdown; also promotes uterine contractions
Breast milk is the ideal nutrition for infants less than 6 months of age. Contains maternal immunoglobulins (conferring passive immunity; mostly IgA), macrophages, lymphocytes. Breast milk reduces infant infections and is associated with lower risk for child to develop asthma, allergies, diabetic mellitus, and obesity. Exclusively breastfed infants require Vitamin D supplementation
Breastfeeding lowers maternal risk of breast and ovarian cancer and facilitates mother-child bonding.
hCG
Source: Syncytiotrophoblast of placenta
Function: Maintains corpus luteum (and thus progesterone) for first 8-10 weeks of pregnancy by acting like LH (otherwise no luteal cell stimulation would lead to abortion)
After 8-10 weeks, placenta synthesizes its own estriol and progesterone and corpus luteum degenerates
used to detect pregnancy bc it appears early in urine
has identical alpha subunit as LH, FSH, TSH. Beta subunit is unique (pregnancy tests detect B subunit).
hCG is elevated in multiple gestations, hydatiform moles, choriocarcinomas, and Down Syndrome
hCG is lowered in ectopic/failing pregnancy, Edward Syndrome, and Patau Syndrome.
Menopause
Lower estrogen production due to age-linked decline in number of ovarian follicles. Average age at onset is 51 years (earlier in smokers)
Usually preceded by 4-5 years of abnormal menstrual cycles. Sources of estrogen (estrone) after menopause becomes peripheral conversion of androgens, increased androgens leads to hirsutism
Much higher FSH is specific for menopause (loss of negative feedback on FSH due to lower estrogen levels)
Hormonal changes: Lower estrogen, Much higher FSH, High LH (no surge), High GnRH
Menopause causes HAVOCS: Hot flashes, Atrophy of the Vagina, Osteoporosis, Coronary artery disease, Sleep disturbances
Menopause before 40 can indicate premature ovarian failure.
Spermatogenesis
Spermatogenesis begins at puberty with spermatogonia. Full development takes 2 months. Occurs in seminiferous tubules.
Produces spermatids that undergo spermiogenesis (loss of cytoplasmic contents, gain of acrosomal cap) to form mature spermatozoon.
Gonium is going to be a sperm. Zoon is Zooming to egg.
Androgens
Testosterone, Dihydrotestosterone (DHT), Androstenedione
1) Source: DHT and testosterone (testis), androstenedione (adrenal)
Potency: DHT > testosterone > androstenedione
2) Function:
Testosterone
- Differentiation of epididymis, vas deferens, seminal vesicles (genitalia, except prostate)
- Growth spurt - penis, seminal vesicles, sperm, muscle, RBCs
- Deepening of voice
- Closing of epiphyseal plates (via estrogen converted from testosterone)
- Libido
DHT
- Early - differentiation of penis, scrotum, prostate
- Late - prostate growth, balding, sebaceous gland activity
Testosterone is converted to DHT by 5a-reductase, which is inhibited by Finasteride
In the male, androgens are converted to estrogen by cytochrome P450 aromatase (primarily in adipose tissue and testis)
Aromatase is the key enzyme in conversion of androgens to estrogen.
Exogenous testosterone leads to inhibition of hypothalamic-pit-gonadal axis. This leads to lower intratesticular testosterone leading to lower testicular size causing azoospermia
Klinefelter Syndrome
(male 47, XXY)
Tesicular atrophy, eunucleoid body shape, tall long extremities, female hair distribituion, may present with developmental delay. Inactivated X chromosome (barr body) is present. Common cause of hypogonadism in infertility work up.
Dysgenesis of seminiferous tubules leads to lower inhibin and increased FSH.
Abnormal Leydig cell function can cause lower testosterone and higher LH leading to higher estrogen.
Turner Syndrome
(Female, 45 XO)
short stature (if untreated), ovarian dysgenesis (streak ovary), shield chest, bicuspid aortic valve, lymphatic defects (webbed neck or lymphedema in hands and feet), horseshoe kidney, most common cause of primary amenorrhea. No Barr body.
Menopause before menarche.
Lower estrogen leads to higher LH and FSH.
Can result from mitotic or meiotic error
Can be complete monosmy (45 XO) or mosaicism (45 XO/46 XX)
Pregnancy possible in some cases (oocyte donation, exogenous estradiol 17B and progesterone)
