Reproduction Flashcards
When are fetuses most susceptible to teratogens?
3-8 weeks (embryonic period)
Branchial pouch derivatives
“Ears, Tonsils, Bottom to top”
1) Middle ear cavity, Eustachian tube, mastoid air cells
2) Tonsils
3) Lower parathyroids, thymus
4) Upper parathyroids
Neural crest cells derivations
MOTEL PASS
Melanocytes, odontoblasts, tracheal cartilage, enterochromaffin cells, laryngeal cartilage/langerhans cells, parafollicular cells of the thyroid, adrenal medulla and all ganglia, Schwann cells, and spiral membrane
Maternal diabetes can cause what problems in utero?
o Caudal regression syndrome (anal atresia to syringomyelia)
o Congenital heart defects (transposition of the great arteries)
o Neural tube defects
o Macrosomia
Causes of polyhydramnios
tracheoesophageal atresia and anencephaly
Dax1 gene
Found on X chromosome
When two X’s are present (females): facilitates ovary development and suppresses testis development
When only one X is present (males): facilitates testes formation
SRY gene
Found on Y chromosome
Inhibits ovary differentiation and induces the development of Sertoli and Leydig cells in the testes
Lymph drainage: Ovaries/testes
para-aortic LN
Lymph drainage: Prostate/cervix
internal iliac LN
Lymph drainage: Distal vagina/vulva/scrotum
superficial inguinal nodes
Lymph drainage: Glans penis
deep inguinal nodes
Where is a varicocele more common? Why?
On the left – the left testicular vein drains into the left renal vein, while the right testicular vein drains directly into the IVC
How do the testes regulate temperature?
Held away from or closer to the body via the spermatic cord
Pampiniform plexus uses countervurrent exchange of heat from the testicular artery to the venous plexus – blood cools before it reaches the testes
Sertoli Cells
form the epithelium of the seminiferous tubules within which the spermatogenic cells undergo mitosis/meiosis to form spermatozoa
Produce inhibin- negative feedback on FSH
Secrete androgen binding protein in response to FSH to maintain local levels of testosterone needed for spermatogenesis
Produce MIS
Tight junctions form blood-testis barrier → prevent autoimmune attack on sperm
Leydig cells
In the connective tissue stroma surrounding seminiferous tubules
Synthesize testosterone in response to LH
erections
tx of erectile dysfunction
parasympathetic activity (pelvic nerve)
Nitric Oxide → inc cGMP → smooth muscle relaxation → vasodilation → erection
o PDE-5 inhibitors (Sildenafil) decrease breakdown of cGMP and are used for erectile dysfunction
Where do FSH and LH act in the testes?
LH acts on Leydig cells –> promote synthesis of testosterone
FSH acts on sertoli cells –> androgen binding protein to concentrate testosterone in seminiferous tubules
Where do spermatozoa mature and develop the capacity for motility?
In the epididymis (due to the binding of glycoproteins to specific regions of the spermatozoan plasma membrane)
Myeloid cells of the seminiferous tubules
Form the outer wall of the seminiferous tubules
Modified fibroblasts that exhibits rhythmic contractions that aid in the movement of spermatozoa through seminiferous tubules
What structure does the urethra pass through in the penis?
The corpus spongiosum
Where is testosterone converted to DHT? By what enzyme?
5a reductase in the skin, prostate, seminal vesicles and liver
Two cell theory
Androgens synthesized by Theca cells (in response to LH) diffuse across the basal lamina to Granulosa cells and is converted to estrogens by aromatase (in response to FSH)
Proliferative Phase
Days 5-14
Estrogen dependent
In response to inc estrogen (from the developing ovarian follicles), stem cells in the stratum basalis undergo rapid proliferation – prep for pregnancy
Secretory phase
Days 14-28 (post-ovulation)
Progesterone dependentIn response to progesterone from the corpus luteum, the endometrial glands become coiled and secrete nutrition
In absence of pregnancy, progesterone levels decrease and the stratum functionalis begins to deteriorate
Coiled arteries in the endometrium close, resulting in ischemia and shedding of the stratum functionalis
What stage are primordial follicles arrested in?
What stage are ovulated follicles arrested in (before fertilization)?
Prophase of meiosis I
Metaphase of meiosis II
Follicle release/Ovulation
Each month, a single antral follicle is selected to be ovulated
The selected ovulatory follicle produces a peak of estrogen which then causes a surge of LH from the pituitary which stimulates release of the oocyte
What causes the inc temperature with ovulation?
Increased progesterone
What stimulates the corpus luteum to produce progesterone?
LH
Progesterone is important for implantation and maintenance of early pregnancy (dec progesterone = dec fertility)
Estrogen and feedback
Normally, estrogen has negative feedback on LH, FSH, and GnRH
Right before ovulation, however, estrogen has positive feedback on FSH, LH, and GnRH
Role of ovarian hormones: estrogen
Follicular maturation
Hyperplasia of endometrium, uterine smooth muscle and vasculature
Stimulates synthesis of estradiol and progesterone receptors on the endometrium
Prepubertal development
Role of ovarian hormones: progesterone
Required for implantation
Stimulation of gland coiling and glycogen secretion in the endometrium
Inhibition of uterine contraction
Inhibition of endometrial sloughing
Origin of placenta
All layers of the placenta are of fetal origin
What produces hCG
The placenta
syncytiotrophoblast cells
What does hCG bind to?
LH receptors (structurally similar, have identical a subunits)
Uterine contraction: estrogen and progesterone
Estrogen: inc contraction
Progesterone: dec contraction
Ratio of E/P is crucial in Braxton Hicks Contractions
What happens to the anterior pituitary when it is exposed to continuously high levels of GnRH? What drug does this?
Inhibition of LH and FSH release
*This is why GnRH agonists are just as effective as GnRH antagonists at reducing testicular activity
Leuprolide
Role of oxytocin in labor
Promotes persistent uterine contractions and acts on decidual tissue to promote release of prostaglandins
Prostaglandins in labor
Promotes uterine contractions
Placenta previa
The presence of placental tissue overlying or proximate to the internal cervical os
Presents as painless vaginal bleeding after 20 weeks of pregnancy
If mom starts hemorrhaging - you MUST deliver
Abruptio placenta
Decidual hemorrhage leading to premature separation of the placenta prior to delivery
Presents as painful vaginal bleeding after 20 weeks of pregnancy
Presentation of placenta previa vs abruptio placenta and risk factors
Placenta previa- painless vaginal bleeding in 2nd/3rd trimester
RF: endometrial scarring, smoking, multiple gestation
Abruptio placenta - painful vaginal bleeding in 2nd/3rd trimester
RF: trauma, HTN, pre-eclampsia, cocaine, smoking
How do estrogen OCPs work?
Prevent release of GnRH and prevent LH and FSH release
Prevents ovulation
How do progesterone OCPs work?
Alters endometrial cervical mucus, fallopian tube motility and peristalsis (Make it a less suitable environment for sperm)
Inhibits GnRH, LH and FSH
Estrogen receptors
a ER - nuclear receptors, alters gene transcription
B ER - nuclear receptors, alters gene transcription
GPR30 - G protein receptor on cell membrane, faster effects**
Contraindications to estrogen therapy
Stoke, prior DVT, estrogen dependent tumor, current pregnancy, smokers >35 yo, migraines with aura, uncontrolled HTN
Instead use progesterone only contraceptive pill
How to medically terminate pregnancy
Mifepristone (RU-486)
Progesterone receptor antagonist- causes contraction of the myometrium and causes detachment from the uterine wall, terminating the pregnancy. BLASTOCYST SEPARATION
Give with misoprostol: a PGE1 agonist that induces uterine contraction
Plan B
Progesterone receptor agonist
Prevents pregnancy- doesn’t terminate pregnancy
Pharm: Induction of labor
Misoprostol: PGE1 agonist - induces uterine contraction and cervical dilation
Dinoprostone: PGE2 agonist- induces uterine contraction and cervical dilation
Oxytocin: ocytocin receptor agonist- induces uterine contraction
Pharm: Inhibition of preterm labor
Terbutaline: B2 receptor agonist that inhibits uterine contraction
Nifedipine: L type Ca2+ channel blocker that inhibits uterine contraction
Where does fertilization usually occur?
In the ampulla of the oviduct
What is the cause of Turner syndrome? Why are these patients short?
Usually due to paternal nondisjunction, but can also have mosaicism (some cells are 45 X,O and others are 46 X,X
Short stature due to loss of SHOX gene (responsible for long bone growth)
Why don’t women with Turner syndrome have secondary sex characteristics?
Ovaries (streak ovaries) are composed of connective tissue with no follicles
No follicles = no estrogen production
What causes gallstones in pregnancy?
due to estrogen upregulation of the HMG-CoA reductase activity, which causes the bile to become supersaturated with cholesterol. Progesterone reduces bile acid secretion and slows gallbladder emptying,
Cause of congenital hydrocele?
Incomplete obliteration of the processus vaginalis causes peritoneal fluid to accumulate within the tunica vaginalis
Can also lead to an indirect hernia
Causes of Down Syndrome
o 95% of cases are due to meiotic nondisjunction
o 4% of cases are due to unbalanced Robertsonian translocation t(14;21)
o 1% are due to mosaicism
Mullerian ducts give rise to:
Uterus, uterine tube, upper 1/3 of vagina (in the absence of MIS)
Regresses in males (due to MIS released from sertoli cells)
Wolffian ducts give rise to:
Epididymis, vas deferens, ejaculatory duct, and seminal vesicles (in the presence of testosterone)
Regresses in females
Urogenital sinus gives rise to:
In the presence of DHT, gives rise to scrotum, penis, prostate, and genital skin
In the absence of DHT, gives rise to clitoris, vagina, and labia
Klinefelter syndrome
47, XXY
Testicular atrophy, gynecomastia, tall, developmental delay
Dec testosterone (due to damaged Leydig cells)
Inc LH and FSH (due to lack of negative feedback)
GnRH Stimulation test
Prepubertal: give GnRH –> no LH secreted
Pubertal: give GnRH –> LH secreted
What structure produces MIS?
Sertoli cells
What male ligament pulls the testes from the abdomen into the scrotum during development?
The gubernaculum
HELLP Syndrome
Hemolysis
Elevated Liver enzymes
Low Platelets
A manifestation of severe preeclampia – need to deliver baby!
PCOS Labs
Elevated LH/FSH ratio
Elevated GnRH
Elevated estrogen and androgens
Hyperinsulinemia
Everything is high!
What can you give a woman with PCOS to help her fertility?
Clomiphene (a SERM that is used to promote ovulation)
Inhibits estrogen in the hypothalamus and prevents normal inhibitory feedback – causes inc LH and FSH, promoting ovulation
What med do you give mothers with preeclampsia or eclampsia to prevent seizure activity?
Magnesium Sulfate
DiGeorge
Chromosomal deletion within chrom 22
Aberrant development of 3rd and 4th branchial pouches
CATCH-22 Cleft palate Abnormal facies Thymic aplasia- T cell deficiency Cardiac defects Hypocalcemia due to lack of parathyroids
What happens to the myometrium of the uterus during pregnancy?
Undergoes hypertrophy AND hyperplasia
Stops undergoing constant rhythmic contractions
What part of the endometrium is shed every month during menses?
Stratum functionalis (superficial layer)
The stratum basalis is retained: serves as a stem cell layer for later regeneration of the stratum functionalis
Prolactin vs oxytocin: breast milk
Prolactin: facilitates milk production- Acts on epithelial cells of the alveoli
Oxytocin: facilitates milk release (milk let down)- Acts on myoepithelial cells
What are the two endocrine glands that make up the ovary?
Follicle: produces estrogen
Corpus luteum: produces progesterone
Location of BPH vs prostatic carcinoma
BPH: in the transitional zone (closer to the urethra)
Prostatic carcinoma: in the peripheral zone
Where is testosterone converted to DHT? By what enzyme?
By 5a reductase
In the skin, prostate, seminal vesicles and liver
Which cells invade the uterine endometrium during implantation?
The syncytiotrophoblast cells
Secondary yolk sac
Site of blood cell formation
Origin of primordial germ cells
Gut derives from the yolk sac endoderm
Fetal blood
Within villi (derived from embryonic mesoderm)
FETAL BLOOD VESSELS ARE COMPLETELY SEPARATE FROM MATERNAL BLOOD (which is within lacunae)
What is responsible for anchoring the conceptus to the uterine wall?
Cytotrophoblastic shell
Shallow invasion/implantation is related to preeclampsia
hCG
Made by syncytiotrophoblast cells of the placenta
Maintains the corpus luteum (and thus progesterone) for first 8-10 weeks of pregnancy
Has an identical a subunit to LH, FSH, and TSH. The unique B subunit is what is detected by pregnancy tests
Hormonal changes in menopause
Dec estrogen
Inc FSH and LH
Inc GnRH
** Very inc FSH is specific for menopause
Effects of dopamine on prolactin
Dopamine inhibits prolactin release by the anterior pituitary
Inc dopamine –> dec prolactin
Dec dopamine –> inc prolactin
This is why galactorrhea is a common side effect in antipsychotics that block dopamine
Why don’t breastfeeding mothers have their menses?
Release of prolactin inhibits GnRH secretion – causes dec in LH and FSH
What does dec AFP in pregnancy indicate?
Down Syndrome
Infertility in cystic fibrosis vs kartagener syndrome
Cystic fibrosis: bilaterally absent ductus deferens
Kartagener: mutation in dynein of cilia (immotile sperm)
1st physical change in female and male puberty.
Females – breast development.
Males – testicular enlargement
How does primary hypothyroidism cause precocious puberty?
There is elevated TSH, which has the same alpha subunit as LH and FSH –> causes gonadal stimulation
What causes gestational diabetes in pregnant women?
human placental lactogen (hPL)
o Causes insulin resistance in mom so that glucose can be mobilized to fetus
Sources of Estrogen production:
- Premenopausal women: E2 (17B estradiol by the ovary)
- Postmenopausal women: E1 (estrone by aromatization in adipose tissue)
- Men: E1 (estrone by aromatization in adipose tissue)
- Pregnant women: E3 (estriol by the placenta)
What prevents lactation during pregnancy?
Progesterone (inhibits prolactin)
Amniotic fluid embolism
o A pulmonary embolism related to pregnacy
Amniotic fluid containing arachidonic acid metabolites is thought to enter the maternal circulation through sites of uterine trauma or cervical lacerations – resulting in an anaphylactoid reaction
o On autopsy will see pulmonary artery branch with swirls of fetal squamous cells
o Can occur during pregnancy or shortly after delivery
o Leads to cardiopulmonary arrest and DIC
Derivations of –
Branchial arches:
Branchial clefts:
Branchial pouches:
Branchial clefts = ectoderm
Branchial arches = mesoderm (Muscles) and neural crest (bones and cartilage)
Branchial pouches = endoderm
CAP = outside to inside
Child presents to your office with microcephaly and intellectual disability. He has epicanthal folds on eye exam. When the child cries, he makes a mewing sound. What disorder is this and what causes it?
Cri du chat (microdeletion of the short arm of chromosome 5)
Child presents to your office with intellectual disability and cardiovascular problems. He is very talkative and you noticed him interacting with multiple people in the waiting room. On exam he has elvin facies. What disorder is this, what causes it and what lab finding would you expect?
Williams syndrome (microdeletion of the long arm of chromosome 7)
Hypercalcemia due to increased sensitivity to vitamin D
Neonate presents with severe intellectual disability, rocker-bottom feet, small jaw, low set ears, clenched hands with overlapping fingers
Edwards syndrome (trisomy 18)
death usually within one year of life
Neonate presents with severe intellectual disability, rocker bottom feet, micropthalmia, microcephaly, cleft lip/palate, holoprosencephaly, polydactyly, congenital heart disease
Patau syndrome (trisomy 13)
Defective prechordal mesoderm fusion – resulting in midline defects
death usually within one year of life
Macrosomia
poor maternal glucose control leads to excessive transplacental glucose transfer to the fetus, which stimulates fetal insulin production – chronic stimulation of the fetal beta cells leads to beta cell hyperplasia and hyperinsulinism → babies can be severely hypoglycemic after birth due to high insulin levles
