CPPS 303 - Reproduction 4: Fertilization and Pregnancy Questions and Answer 2023

CPPS 303 - Reproduction 4: Fertilization and Pregnancy Questions and Answer 2023 Where does fertilization occur In the ampulla of the fallopian tube - upper third of the fallopian tube How long does it take for the egg to travel from the place of fertilization to the uterus for implantation? 7 days Capacitation Once in the female reproductive tract, the protective coat on sperm head is removed - It allows the head to penetrate the zona pellucida - Capacitation allows the acrosomal enzymes to be released later Acrosome The end of the head of sperm Components of the zona pellucida 3 glycoprotein layers - ZP1(outer), ZP2, ZP3(inner) Acrosomal Reaction 1) Receptors on the sperm head bind to ZP3 2) A rise in Ca2+ inside the sperm will trigger the release of the acrosomal contents into the oocyte 8 Steps in fertilization 1) Sperm head attaches ti zona pellucida - Receptors on the PM of the sperm bind to ZP3, triggering acrosomal reaction 2) Acrosomal reaction occurs - Increase in Ca2+ causes acrosomal contents to be expelled into oocyte 3) Hydrolyzing enzymes in the acrosomal cap facilitate the sperm to penetrate the zona pellucida 4) Cell membranes of sperm and oocyte fuse - IP3 is formed, causing Ca2+ release from internal stores 5) Increase in Ca2+ triggers oocytes 2nd meiotic division and cortical reaction - Granules exocytose and cause the zona pellucida to harden 6) 2nd meiotic division finishes and nucleus decondenses = female pronucleus (1N) - Oocyte divides into mature oocyte and 2nd polar body 7) Sperm nucleus deondenses into the male pronucleus (1N) 8) Male and female pronuclei fuse, forming a zygote - Zygote (2N) = 46 chromosomes Cortical Reaction 1) A rise in Ca2+ in the oocyte triggers reaction 2) Electron dense granules in the oocyte exocytose 3) Exocytosis of the granules releases enzymes that act on glycoproteins in the zona pellucida, causing them to harden, preventing any more sperm from entering Overview of oogenesis and arresting points Fetal oogenesis - Primary oocyte begins 1st meiotic division and is arrested in prophase Puberty oogenesis - Primary oocyte finishes 1st meiotic division - 2nd meiotic division begins and is arrested in metaphase Fertilization - Fertilization triggers completion of the 2nd meiotic division into a mature oocyte Morula Stage Fertilized ovum resides in fallopian tube and continues to divide (12 or more cells) - receive nourishment from fallopian tube secretions Morula will move through isthmus to uterus by beating cilia and contractions Blastocyst Ball like structure w fluid-filled inner cavity - Transforms from morula to blastocyst in the uterine cavity - It freely floats for about 72 hours before it implants to the uterus 7 Days after ovulation Progesterone from corpus luteum vascularize the endometrium to prepare for pregnancy Predecidulization 9-10 days after ovulation - Stromal cells transform into rounded decidual cells - Decidual cells spread across superficial layer of endometrium making it more compact (zona compact), separating it from deep spongy later (Sona spongiosa) Decidualization The predecidual changes are sustained and extended What does the corpus luteum secrete Progesterone - Maintains endometrium What does the uterine glandular epithelium secrete? Steroid dependent proteins for nourishment, growth and implantation What does the Endometrium Secrete? - Cholesterol - Steroid - Other nutrients Maternal Cellular Immune system may recognize the blastocyst as a enemy and kill it Immunosupressive Agents Blastocyst secretes hCG that has immunosupressive characteristics - This depresses the mothers immune system so she doesn't reject the blastocyst Some women have hypersensitive immune systems, and will still reject the blastocyst hCG Human Chorionic Gonadotropin - Sustains corpus luteum after maternal LH levels fall - Has growth promoting ability - Acts as an autocrine growth factor that promotes trophoblasts (outer layer of blastocyst that implants into endometrium) Blastocyst during implantation embeds in uterine lining - adheres to epithelial cells - Breaks through basement membrane - invades stroma In vitro fertilization-embryo transfer (IVF-ET) Oocytes are removed from women, fertilized in vitro, then the embryos are implanted back into women Steps to IVF-ET (5) 1) Ovarian Stimulation 2) Cycle Monitoring 3) Oocyte retrieval 4) Insemination 5) Embryo transfer 1) Ovarian Stimulation Females only develop 1 dominant follicate each cycle, but success rate isn't high so more are needed - GnRH analogues are given to gonadotropins to down-regulate hypothalamic-pituitary axis (prevents premature LH surge and ovulation) - Give high dose of external gonadotropin(LH, FSH) to trigger the release of many dominant follicles 2) Cycle Monitoring - follicular growth is monitored by sonographic imaging and estradiol levels - When folliculogenesis is indicated, LH surge is stimulated by injecting hCG - LH surge will complete maturation of multiple follicles and oocytes - Oocytes must be removed after maturation, but before ovulation (34-36 hours) 3) Oocyte retrieval - Oocytes are obtianed by a probe and sucked up a needle - follicular fluid, eggs and other follicular cells are separated - Eggs are washed and prepared for insemination 4) Insemination - Purified sperm in inseminated into egg - Fertilization rates = 60-85% intracytoplasmic sperm injection (ICSI) Micro-manipulation techniques inject sperm into the cytoplasm with higher accuracy - Used when there is low sperm count - Fertilization rates = 60-70% 5) Embryo transfer After 48-120 hours of cell cultiring, the embryos are transferred to the uterus - Inserted with catheter into uterine cavity - at the 4-8 cell stage - Supplemental progesterone is given to support implantation and pregnancy Tubal Embryo Transfer (TET) Sometimes the embryos are inserted into the fallopian tub - fallopian tube contributes to the early development of the embryo Gamete intrafallopian transfer (GIFT) Another IVF technique - Both the oocyte and sperm are injected into the fallopian tube, letting fertilization occur there Which peptide hormones does the placenta make - Human chorionic gonadotropin (hCG) - Human chorionic somatomammotropin (hCS) Human Placental Lactogen (hPL) hCS 1 and hCS 2 - related to growth hormone and prolactin - Convert glucose to fatty acids/ketones - Helps to facilitate energy supply to developing fetus - Preferentially distribute nutrients to fetus over mother hPL anti-insulin effects Reduce maternal insulin sensitivity, reduces the mothers utilization of glucose to ensure adequate fetal nutrition - Causes hyperglycemia and gestational diabetes - Enhances maternal lipolysis Gestational Diabetes diabetes during pregnancy - There is desensitization of the insulin receptors from overproduction of insulin What causes overproduction of insulin Release 1) Glucose 2) ACh 3) Glucagon (β-adrenergic agonists), GIP, hCG, hCS, hPL Glucose causing insulin release process 1) Glucose binds to GLUT2 receptor 2) Glucose is degraded in glycolysis and CAC to produce ATP 3) ATP will inhibit the K+ channel on membrane - This depolarizes the membrane 4) Depolarization activates voltage-gated Ca2+ channel on membrane - influx of Ca2+ into the cell 5) Increase in Ca2+ will promote release of more Ca2+ from ER 6) Increased Ca2+ levels will promote exocytosis of insulin filled vesicles ACh causing insulin release process 1) ACh binds to GPCR 2) Gq is activated 3) Gq activated PLC 4) PLC cleaves DAG and IP3 - IP3 causes release of Ca2+ from ER - DAG activated PKC, which promotes exocytosis of insulin Glucagon (β-adrenergic agonists), GIP, hCG, hCS, hPL causing insulin release process They are all Gs agonists 1) Ligands bind to GPCR 2) Activates G