Implantation PDF

Pre-Implantation Zygote Morula (8-16) Blastocyst (32-64) - trophoblast, embryoblast (inner cell mass) Implantation and Embryonic Phase D12 after ovulation Metabolic needs of zygote met by secretions of oviduct and endometrium Endometrium is receptive for narrow window of 3D coinc...

Pre-Implantation Zygote Morula (8-16) Blastocyst (32-64) - trophoblast, embryoblast (inner cell mass) Implantation and Embryonic Phase D12 after ovulation Metabolic needs of zygote met by secretions of oviduct and endometrium Endometrium is receptive for narrow window of 3D coinciding with maximum progesterone secretion via corpus luteum Integrins on trophoblast allow blastocyst to attach to receptors on endometrium If endometrium is not mature, blastocyst detaches and floats to lower level of uterus to try to implant again Process: 1. Trophoblast (with integrins) adheres to endometrium (with receptors) 2. Trophoblast proliferates and becomes: cytotrophoblast (inner) and syncytiotrophoblast (outer) 3. Decidualization response: Syncytiotrophoblast cells invade endometrial cells until blastocyst is buried 4. Endometrial cells cover blastocyst forming a seal 5. Trophoblast initiates local changes in endometrium causing: a. Changes in matrix composition b. Change in stromal cell morphology c. Sprouting and ingrowth of capillaries 6. Trophoblast cells produce human chorionic gonadotropin (hCG) → signals to CL to continue production of progesterone and oestrogen until 8W Implantation Issues Even with healthy embryo, failure rate is high ○ >⅔ blastocysts fail to implant ○ ⅓ of implanted embryos miscarry Lack of hCG → decrease in oestrogen and progesterone → sloughing of endometrium Aetiology: largely unknown Scarring of uterus - Pelvic inflammatory disease Hormonal imbalances - PCOS Non-receptive endometrium Ectopic pregnancy - outside uterus Placenta praevia - blastocyst implants near opening of cervix ○ Placenta cover opening to vagina ○ Placenta separates prematurely The Placenta Function Provides all nutrients and removes all fetal wastes ○ Nutrients: glucose, lipids, minerals, oxygen ○ Wastes: urea, heat, CO2 ○ Fetus is Independent of fetal brain, lung, gut, kidneys dependent on liver/spleen (haematopoiesis, cardiovascular system and placenta Partial immunological barrier (fetus is foreign to mother) Synthesises and secretes hormones required for maintenance of pregnancy and growth of fetus ○ Steroids - progesterone, oestrogen ○ Prostaglandins (PGE2, PGF2alpha) ○ hCG, hPL ○ CRH, GH, ACTH, GnRH, TSH ○ Relaxin (also by corpus luteum) Doppler ultrasound can test growth of fetus and function of placenta The Placenta Maternal blood via spiral arteries pools in maternal blood pool Fetal circulation passes through umbilical cord and enters chorionic villi - where exchange occurs Formation of the Placenta 1. After implantation, syncytiotrophoblast cells form multinucleated wall 2. The decidualization response has damaged uterine blood vessels 3. Blood from uterine spiral arteries pool in lacunae (spaces) of syncytiotrophoblast - contains maternal blood 4. Lacunae merge 5. Cytotrophoblast sends cells to anchor placenta to endometrium → forms 1˚ chorionic villi 6. W3: Fetal mesoderm layer expands under cytotrophoblast to → form 2˚ chorionic villi 7. Blood vessels enter villi → 3˚ chorionic villi 8. Cytotrophoblasts form cytotrophoblastic shell a. Villi attached to this are called anchoring villi b. Villi branching off sides are called branching villi (main site of exchange) 9. Fetal blood flow established by W4 Formation of the Placenta Conversion: 2nd differentiation of cytotrophoblast cells Fully matured maternal blood flow develops by W10-12 Forms extravillous trophoblast cell ○ Cytotrophoblast cells detach from villi and migrate into maternal endometrium and myometrium ○ Cells that migrate along maternal spiral arteries become endovascular extravillous trophoblast Functions to convert maternal vessels into low pressure, high capacity circulation via: ○ Loss of smooth muscle, endothelial lining, vasoreactivity Failure associated with complications as pressure is too high (breaking villi → poor diffusion) - pre-eclampsia, intrauterine growth restriction of fetus  Maternal to Embryonic Nutrition Histiotrophic nutrition Haemotrophic nutrition - blood-borne via placenta Before implantation → early implantation Complete by W14 Endometrial fluids, mainly from uterine Maternal and foetal circualtion are separate: glands ○ Uterine a./v. Between mother/placenta Materials pass through thin layer of ○ Umbilical a./v. Between fetus and placenta trophoblast and distributed via diffusion ○ Arteries away from hearts toward placenta As mesoderm develops, blood vessels ○ Umbilical a. Are paired, umbilical v. is singular develop and link up to form a network Transport: ○ Simple diffusion - low molecular weight and non-polar molecules ○ Facilitated diffusion - glucose, lactate ○ Active transport - amino acids, Fe, Ca, P, vitamins Permeable to alcohol, nicotine, drugs Hormones During Pregnancy Hormone Produced by Function hCG Blastocyst Maintain CL → secretes progesterone and oestrogen to Can be found 2-3D post-implantation in maintain pregnancy maternal urine Progesterone Corpus luteum (first 50days) Keeps myometrium and uterine muscle inactive (P4) Placental trophoblast (antagonises oestrogens) Promotes uterine growth with oestrogens Progesterone dominance: increase in Relaxation of smooth muscle in genital, vascular, progesterone secretion over gestation is urinary and GI tracts 10x that of oestrogens Extended secretion critical for initiation and maintenance of pregnancy If levels fall or receptor is blocked, pregnancy fails - progesterone receptor blockers (Mifepristone) for medical abortion of gestations