REPRODUCTION FEMALE REPRODUCTION A physician named Dr.

Nagel assumed a woman cycle is 28 day long

MENSTURAL CYCLE Days 1-10 Proliferative/Follicular stage o Estrogen is responsible for this stage o cell number and size Days 10-14 Ovulatory stage o LH is the predominating hormone o It is the stage responsible for deposition of lipids vacuoles o Blood vessels begin to form Days 14- 28 Luteal/Secretory stage o Progesterone is the predominating hormone o This stage is fixed in most women around the world It is the proliferative stage that varies the most o ovulation is always 2 wks- menstrual cycle Estimated day of confinement = When is my baby due? o Nagels Rule: 1st Find out when her last menses began 2nd Add 9 months or subtract 3 months 3rd Then add 1 wk o Example: Last period began Dec 10th Add 9 months = August 10th Add 7 days (1 week) = August 17th This will be within +1 2 Weeks Normal gestation = 37-42 wks. o preterm <37 wks. o post term > 42 wks 1

Embryology 1 round of mitosis 4N (92chromones) 1 round of meiosis 4N o 10 Oocyte o Prophase until ovulation Meiosis II (2n) o 20 Oocyte & Polar bodies o Arrested in metaphase until fertilization 5 Months gestation- the female already has her eggs (largest amount of eggs) When she is born she has 400,000 eggs remaining, arrested in prophase Every month since puberty 8-10 follicles will start developing usually one is fertilized

all

NONDISJUNSTION 2

 Always occurs more frequently in dad because of hundreds of sperm BUT TRANSMISSIBLE non-dysjunction is transmitted through mom

FEMALE ENDOCRINE: Menstrual Cycle DAY 1 of the menstrual cycle = 1st day of bleeding LAST DAY of menstrual cycle = 1st day of bleeding MENSES o Bleeding lasts for approx. 3-5 days

PROLIFERATIVE/FOLLICULAR PHASE: DAYS 1 10 Increase in cell size and number ESTROGEN dependent At the start of the cycle, the hypothalamus secretes GnRH and stimulates the pituitary gland to secrete FSH & LH LH stimulates the Theca externa to release androgen (progesterone) The androgen released acts as a substrate for FSH to stimulate the Theca interna to secrete ESTROGEN Theca interna also secretes FSH/LH and triggers development of one or more follicles in the ovary As the follicle grows in size, estrogen is secreted Inhibits further Stimulates the pituitary Stimulate growth and production of FSH gland to secrete LH repair of the uterine lining LH SURGE (endometrium) Positive Feedback Breasts Uterus Cervix Ductal Growth d/t estrogen Decidua functionalis Thin mucosa Once the estrogen is finished here at day 10 positive feedback to hypothalamus One Graffian follicle is produced on day 10 This follicle takes most of the blood supply because it is the largest and then the others scar up and die = corpus albicans The Graffian follicle will continue to secrete estrogen Proliferative/Follicular Phase

FSH/Estrogen

Progesterone

DAY 10

Day 14

OVULATORY STAGE: DAYS 10 14 As the follicular stage progresses, the developing follicle increases in size and becomes a mature follicle Oestrogen levels increase rapidly Triggers further release of LH (high concentration of LH in the blood) Triggers a sudden release of FSH for final development of follicle (no negative feedback peaks at Day 14) FSH/LH continue to stimulate the graffian follicle to secrete estrogen this estrogen stimulates an upregulation of LH receptors on the Theca interna and pushes the ovum out The Theca externa becomes the corpus luteum and begins to secrete Progesterone Ovulation Oocyte leaves the ovary and passes into the fallopian tube Female is fertile

Ovulatory Phase

LH

FSH

Progesterone

DAY 10

Day 14

LUTEAL PHASE: DAYS 14 28 7

Progesterone Dominant Luteal Phase The high concentrations of LH that brings about ovulation has an affect on the follicle cells that remain in the ovary Follicle becomes corpus luteum Corpus luteum secretes some estrogen and a large amount of progesterone Progesterone stimulates mammary glands and uterus in anticipation of pregnancy Breasts: Glandular growth (breasts enlarge 2 weeks before menses) Uterus: Formation of spiral arteries & (+) lipid/glycogen deposition Cervix: Thickened mucosa If the Oocyte is not fertilised within 36 hours, it dies At day 28, a lack of progesterone brings about another menstruation High concentrations of estrogen and progesterone inhibit production of FSH and LH Without FSH and LH the cells of the corpus luteum gets smaller b/c there is no progesterone to support spiral arteries (sloughs off) and less progesterone and estrogen is secreted With less estrogen and progesterone, the FSH is no longer inhibited, and the cycle can start again

HORMONAL SUMMARY 8

Recall at menses there is a lot of bleeding due to the formation of spiral arteries, however, if there is TOO MUCH BLEEDING one can administer additional estrogen to stimulate more endometrium to conpensate Contraceptives o Depovera Composed of PROGESTERONE ONLY Recall that Progesterone can inhibit LH, which is responsible for Ovulation Therefore, if you able to block LH completely = No Pregnancy SE: Think about unopposed Progesterone effects Labile Weight Gain No cardioprotection b/c not enough estrogen around

MALE REPRODUCTIVE SPERMATOGENESIS Endocrine Mama Sertoli

Spermatogenesis is promoted by Testosterone o Male will be sterile if he doesnt have testosterone Or if testosterone receptors are not working o Need LH to stimulate Leydig cells to produce testosterone o FSH stimulate Sertoli cells Release inhibin which will illicit negative feedback of FSH o Mama Sertoli She protects the sperm!!! Maintain blood-testes barrier protect sperm against lymphocytes that will attack them Help mature the sperm o Spermatogonium are located at the base of the testis o They go onto mature to spermatids Located at the surface and enter the epididymis Spermatogenesis takes place in the Testes o Speratotids found closer to lumen o mature sperm are stored in epididymis until ejaculation occurs o Every day 20-40 million sperm mature o Takes 41-72 days for sperm to reach maturation

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Speramotgenesis Spermatogonia o 1 mitosis o 10 meiosis I (46 choromosomes) = Spermatocyte o 20 meiosis (23) 1n = Spermatid o Spermatocyte when its mature Measure of virility in a male: o Has to have at least 20 million sperm/cc o A minimum 4-5 cc of semen per ejaculate = 100 million sperm o Cannot have more than 40% abnormal forms Natural selection o Minimum 30-60% still motile on a glass slide for 5 minutes o pH has to be high because of HCO3 Infertility o Is being unable to conceive after 12 months of unprotected sex. o 50% of the time, its the males problem = MCC of infertility o 30% is the female problem PID is #1 cause in a FEMALE be careful of Chlamydia Prepare for battle: o MAMA SERTOLI tells them to get ready 100 million of ya are goin out, and none of ya are coming back! st o 1 must go to the Seminal vesicle Pick up semen for camouflage to protect against acidic vagina Fructose as power bars o Next the Prostate pick up Zinc for capacitation (remove semen off the sperm) Pick up acid phosphatase eat through cervical mucus = wire cutters Need hyaluronidase eat through connective tissue (corona radiata) to get to ovum. o 3rd go to the Bulbourethral (Cowper) glands HCO3- - neutralize acid in vagina HCO3- Bombs
ejaculatory duct

o Get to the Ejaculatory duct This is connected to the urethra The duct has a one way flap that closes bladder urethra Squeezing the head of the penis as long as sperm are in the ejaculatory duct retrograde ejaculation The woman should squeeze the head of the penis Premature ejaculation is #1 problem in young males get too excited Valve closes bladder to urethra when ready to ejaculate Autonomic dysfunction can cause retrograde ejaculation as well Ex. UA on a diabetic patient shows sperm 11

Fertilization 3 reactions occur o Activation- Zn used to peel semen off o Acrosomal reaction dart in to release enzymes on corona radiata o Crystalization reaction prevent polyspermy Only one gets in to and through the Zona Pelluicda

Zygote o 2 cell stage o Identical twins can form at this stage split into2 perfect halves Will alwys be MONOCHORIONIC 1 egg:1sperm o Fraternal twins will be several eggs fertilized different sperm Will have more than one chorion 2 sperm:2 eggs

by

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 Morula o 16 cells o enters uterus Blastula o 256-512 cells o Stage of implantation o 70% occur in posterior wall of uterus.

Trophoblast o Arias Stella reaction When the baby and mother meet indicative of implantation o Baby will start growing into mom inner lining baby vili will be growing from baby into the mother Outer layer mom

Phycomelia = limb abnormalities caused by Thalidomide

Implantation (1 week after fertilization day after of ovulation) o Placenta will produce hCG Detectable in the blood at 7 days after fertilization Maintains corpus luteum Progesterone Estrogen Sensitize moms TSH receptor to BMR Morning sickness b/c hCG stimulates the GI tract hCG Will double in amount every 2 days in first trimester until week 12 13

 Peaks at 2 weeks (when placenta is fully formed) hCG can be used as measurment of fetal growth o Fundal height is a better estimation o Fetus should grow 1cm / week Pelvic rim = 12 cm Umbilicus = 20 cm. PATHOLOGY Molar Pregnancy o Uterus rising more than normal because hCG is rising faster than normal o HTN first trimester o HCG rising more than usual o subunit of hCG, FSH, LH, and TSH are exactly the same Must measure subunit Different types: o Complete Mole 46 XX 2 sperm no egg Looks like ball of grapes Snow storm appearance on sonogram M/C complication- uterine invasion Risk of choriocarcinoma is 2% Treatment: D&C = scoop it out Follow HCG levels for at least 1st 6 months If continues to rise, use methotrexate to kill left over tissue. o Incomplete Mole 2 sperm + 1 egg, M/C XXY 69 chromosomes Can have complete baby, or parts of a baby Need sonogram to identify D&C fetal parts Full baby can go to term and take out mole later. Mom can have risk of hypertension during pregnancy Effects of o o o o o Effects of o progesterone in pregnancy woman appetite acne d/t stimulation of sebaceous glands RBC mass by 30% All steroid hormones are mineralocoticoids. Mineralocorticoids retain water = raise plasma volume by 50% HCT will go down dilutional anemia of pregnancy = normochromic estrogen in pregnancy woman muscle relaxant constipation relaxation of GI Hips spread out. Blood vessels dilate SED rate due to protein production in the liver Proteins are also clotting factors 14

DVTs PE

Effects of estratriol major estrogen secreted by placenta Inhibin o inhibits FSH wont menstruate anymore Oxytocin milk let down Human Placental Lactogen, HPL o responsible for blocking moms insulin receptors insulin levels like DM type II Gestational Diabetes Do a Glucose tolerance test Complications of pregnancy Preterm bleeding prior to 20 wks Called threatened abortion Do sonogram o If baby is fine and cervix is closed STILL threatened abortion Treatment bed rest o If baby is fine and cervix is open Inevitable abortion o If there are fetal remnants and open cervix Incomplete abortion (little bit of baby left) Need to treat with D&C before placental remnants get infected o No fetal remnants, cervix is open Complete abortion o No fetal remnants and cervix is closed Abortion happened a long time ago Missed abortion Chromosomal abnormalities are responsible for most 1st trimester abortion Term Bleeding Bleeding near term pregnancy 37-40 wks o Placenta Previa Painless Bleeding Placenta implants above the cervical os. As the cervix will dilate it will rupture the placental arteries Apt test to differentiate baby bleeding from moms bleeding o Will detect Hg F o -Apt test bed rest and monitor, mom is bleeding Transfuse mom if necessary o +Apt test baby is bleeding,

PGF is responsible for placental separation

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o Placenta increta Placenta implants on endometrium o Placenta accreta Placenta attached to myometrium Need to do Hysterectomy after delivery o Placenta Percreta Placenta attached to serosa Periphery Found on Biopsy Need Hysterectomy after delivery Abruption Placenta o Placenta is torn away from mom painful bleeding o Possible DIC o Surgical emergency and need C-Section There is a clot formed between the placenta and baby, cutting off O2 to the baby Recall that Ischemia always painful Primary reason for ischemia is hypertension Other risk Factors: EtOH, Smoking, Cocaine, Diabetic moms Vaso previa o Artery of placenta hanging out of cervical os Monitor!!! When the placenta separates approx. 100 cc of babys blood goes to mom o Think about Rh Sensitivity o If it is > 100 cc check with Kirby Bauer test Dilutional test to how much blod went across to mom If the moms veins are open amniotic fluid can cross o Therefore, amniotic fluid embolism can occur o Amniotic fluid is very sticky so it can clot everywhere o It will present with the mom in SOB can offset a PE If mom hemorrhages for any reason lose blood supply to the Pituitary gland o Panhypopituitarism (Sheehans) Loss of entire pituitary Sheehans is panhypopituitarism is in the post-partum setting Hormones will disappear in the same order: Prolactin o No breast milk in Sheehans Growth Hormone o No symptoms in adults FSH/LH o Woman will present as amenorrhea o Man will present with impotence. TSH

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o Becomes hypothyroid Permissive under normal condition Cant live without TSH ACTH o Permissive under stress Cant live without it under stress Amenorrhea

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Never had a period at or after age 16 MCC = anovulatory cycles There is an estrogen effect without progesterone affect Prove it!! Proven by Provera challenge (Progesterone) Give Provera 5mg x 5 days and stop If she bleeds, she has estrogen without progesterone Doesnt need treatment will resolve spontaneously with age If she doesnt bleed there is something wrong with pituitary or ovary Needs a work up Measure FSH If in FSH = Ovary problem If inFSH = Pituitary problem

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Used to menstruate, but now stopped Most common cause is Pregnancy 1st test to do check -hCG aka pregnancy test

Dysmenorrhea o Painful menstrual cramps o #1 reason to miss school or work o PGF is responsible for that o Mid-cycle pain = Mittle Schmerz pain o Treatment: o NSAIDS Naproxen o BCP to slow it down o Must have parental consent for treating dysmenorrheal at a young age, but do not need parental consent for only birth control Menorrhagia = Heavy menstrual bleeding Causes MCC is Obesity o Adipose tissue makes excess estrogen that is not controlled #2 is Fibroids leiomyomas Submucosal gives the most bleeding Subserosal will produce pain and pressure from compression of structures in pelvis Treatment o Weight loss o BCP to suppress cycle until loss of weight o Suppress GnRH with Leuprolide (GnRH analogue) that desensitizes the receptor BCP to suppress cycle Leuprolide Surgery is the last resort (cant get the submucosal) 17

#3 Adenomyosis Growth of endometrial tissue in the muscle layer = Surface area If mom has DES exposure, then it could cause increased risk in daughters #4 Endometriosis retrograde menses Heavy menstrual bleeding that is painful. Endometriosis affects Ovary, Uterosacral ligament, Cul-de-sac Described as powder burns or chocolate cysts. These will bleed like other endometrial tissue Will cause adhesion formation If a female complains of chronic pelvic pain it is Endometriosis until proven otherwise. Proven by laparoscopy Be careful because microscopic endometriosis exists so need to biopsy above areas as well.

BCP to suppress cycle Leuprolide Surgery is the last resort

Treatment: BCP to suppress cycle Leuprolide Danazol potent androgen and throws off balance SE: Memory loss

Metrorrhagia Bleeding in between periods Present with Postcoital bleeding in young women Cervical CA until proven otherwise o Hysterectomy indicated Endometrial CA o Metrorrhagia in every woman over 40 is always endometrial CA until proven otherwise o Next step is perform a endometrial biopsy MENOPAUSE Average Age = 51 year old in America Best way to find out = Measure FSH o If > 50 = Menopause o 30 50 = perimenopause Estrogen Replacement o Benefit Stops symptoms Prevents Coronary Heart Disease 30 micrograms Prevents agains Osteoporosis 60 micrograms o Roloxifen Anti-estrogen at the breast and pituitary Pro-estrogen at the bone good for osteoporosis If uterus is still intact cycle with progesterone to balance out estrogen effect Dyspareunia Painful intercourse Young women = Vaginismis (vaginal spasms) 18

o Needs to relax Middle age = Cervical problem > 50 = Menopause because vagina dries out o Treatment estrogen cream

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