Lecture 4 Flashcards
Where does fertilization occur?
What must happen for fertilization to occur?
What is capacitation?
Fertilization occurs in the ampulla, the upper third of the Fallopian tube or the oviduct
For fertilization to occurs sperm must undergo further maturation (capacitation) in the female reproductive tract
Capacitation is the physiological process by which spermatozoa acquire the ability to penetrate the zona pellucida of the ovum (removal or modification of protective protein coat from sperm membrane)
Slides 1-2
What are the 8 steps of fertilization?
- Sperm cell weaves past follicular cells and binds to the zona pellucida
- Rise in [Ca]i in sperm triggers exocytosis of acrosome (has hydrolytic enzymes)
- Hydrolytic enzymes contained in the acrosomal cap are released (they dissolve the zona pellucida), the whip tail of sperm pushes it to oocyte membrane
- Head of sperm now sideways, microvilli on oocyte surround sperm head. The two membranes fuse and contents of sperm enter the oocyte
- Rise in [Ca]i inside oocyte triggers exocytosis of granules that release enzymes that lead to changes in zona pellucida proteins causing it to harden (prevent entry of other sperm)
- Rise in [Ca]i inside oocyte indices completion of the second oocytes meiotic division and formation of second polar body
- Head of spermatocyte enlarges to become the male pronucleus
- Male and female pronuclei fuse
Slides 3-8
How does the female reproductive system prepare for implantation of embryo?
The fertilized ovum resides in the Fallopian tube for about 3 days, during which it develops to the morula stage (mulberry shapes solid mass of 12 or more cells), receiving nourishment from Fallopian tube secretions
Fertilized ovum is later propelled through the isthmus of the Fallopian tube to the uterus by beating of the cilia of the tubal epithelium and contraction of the Fallopian tube
Slide 9-10
How is a blastocyst formed in preparation for implantation of the developing embryo?
After modulatory rapidly moves through the isthmus to uterine cavity, it floats freely in lumen if uterus and transforms to a blastocyst (ball like structure with a fluid filled inner cavity
Blastocyst floats freely for about 72 hours before it attaches to endometrium (implantation of human blastocyst normally occurs 6-7 days after ovulation)
What is predecidualization?
Predecidualization happens 9-10 days after ovulation
Stromal cells transform into rounded decidual cells
These spread across the superficial layer of the endometrium making it more compact (zona compacta) and separating it’s from the deeper spongy layer (zona spongiosa)
What does the blastocyst do for implantation and to stay alive?
The blastocyst secretes substances that facilitate implantation
For the blastocyst to survive it must avoid rejection by the maternal cellular immune system, it does so by releasing immunosuppressive agents
Early blastocyst secretes human chorionic gonadotropin (hCG), closely related to LH
It sustains corpus luteum in the face of rapidly falling levels of maternal LH
Also has immunosuppressive characteristics, growth promoting ability and autocrine growth factor
Slide 11-12
What is in vitro fertilization and embryo transfer?
In vitro fertilization is a procedure in which oocytes are removed from a woman and fertilized with spermatocyte under laboratory conditions
Used in disorders that impair normal meeting of sperm to egg, male factor infertility
Many oocytes are needed for this since success rate is under 100%, so give high dose of gonadotropin to trigger development of many follicles (combo of LH and FSH)
Must monitor size and growth of follicles
Slides 13-14
What are the 6 steps of in vitro fertilization?
- Ovarian stim- produces many oocytes by stim with gonadotropins (FSH and LH)
- Cycle monitoring- monitor follicular growth
- Oocyte retrieval- oocytes recovered by aspirating them from individual follicles
- Insemination- purified sperm are used to inseminate egg, fertilization can be detected by the presence of 2 pronuclei in the egg cytoplasms
- Embryo transfer- after culturing for 48-120 hours, embryos are transferred to the uterus
- Gamete intrafallopian transfer (GIFT)- oocytes and spermatocyte cells are directly transferred to the Fallopian tube, where fertilization occurs
Slides 13-14
What hormones does the placenta make?
Placenta makes many hormones
hGC and human chorionic somatomammotropin (hCS)
hCS 1 and 2 are polypeptide hormones that are related to growth hormone and prolactin, they convert glucose to fatty acids and ketones and development of maternal mammary glands during pregnancy
Slides 15-17
What is the maternal-placental-fetal unit?
During pregnancy, progesterone and estrogens rise to levels that are higher than their peaks in normal cycle
Corpus luteum lasts about 12 days after which it begins to demise as the levels of LH decline
Progesterone reduces uterine motility and inhibits propagation of contractions
Developing placenta increases production of progesterone and estrogens so that by 8 weeks of gestation, the placenta a becomes the major source of these steroids
Slides 18-19
How does the mother-placental-fetal unit overcome the placental shortcomings (lacks adequate cholesterols synthesizing capacity, lacks 17α hydroxylase, 17, 20- desmolase, 16αhydroxlase)
- The mother supplies most of the cholesterol as LDL particles so the placenta can generate large amounts of progesterone and export it to the mother (this maintains progesterone levels after corpus luteum becomes adequate)
- The fetal adrenal gland and liver supply the 3 enzymes the placenta lacks
Slides 20-22
How does the fetus and it’s placenta solve the problems of the fetus lacking enzymes that catalyze 2 step estrone production and if it were able to create progesterone it would be exposed to too many hormones?
(3 strategies)
- Since fetus lacks 2 enzymes to produce estrone, it never makes anything beyond DHEA and 16α-hydroxy-DHEA
- Placenta is massive sink for the weak androgens that the fetus synthesize, thus preventing the masculization of female fetuses
- The fetus conjugates the necessary steroid intermediated to sulfate, which greatly reduces their biological activity
Slides 20-22
What is the physiological response of the mother to pregnancy?
Duration of pregnancy is approx 266 days (38 weeks) from ovulation or 280 from first day of last menstrual period
Mother undergoes many profound adaptive changes in her CV system, fluid volume, respiration, fuel metabolism, nutrition
Maternal blood volume increases during first trimester, second trimester, and at a slower rate third trimester (blood may increase from 45-100%)
Mean arterial pressure drops mid pregnancy then goes up third trimester
Increase levels of progesterone, alveolar ventilation, demand for protein, iron, folic acid
Slides 23-25
How does posture affect cardiac output and pregnancy?
Posture has major effect in cardiac output
In late pregnancy, cardiac output is typically higher when the mother is in the lateral recumbent position than when she’s in the supine position
Posture also effects arterial blood pressure
Blood pressure in brachial artery is highest when sitting, lowest when in the lateral recumbent position, intermediate when mother is supine
Slide 24
What is the path of arachnoidonic acid and prostaglandins?
In direct pathway, an agonist binds to a receptor that activates phospholipase-A2 (PLA2), which releases arachidonic acid (AA) from a membrane phospholipid
2 other pathways slide 26
Arachidonic acid leads to production of prostaglandins, leukotrienes, prostacyclins, and thromboxanes
Prostaglandins act by a paracrine mechanism for uterine smooth muscle contraction
Slides 26-29
Slide 31
What is parturition?
Throughout most of pregnancy, uterus is quiescent (progesterone and relaxin may promote this)
Weak and irregular uterine contractions occur throughout the last month of pregnancy
Eventually series of regular, rhythmic contractions initiate labour
Progesterone plays an important role in maintaining length of gestation in primates
Slide 30
What are the stages of labour?
Stage 0- uterine tranquility and refractoriness (non responsive) to contraction
Stage 1- uterine wakening, initiation of parturition, extending to complete cervical dilation, increase in # of gap junctions between myometrial cells, increase in the # of oxytocin receptors
Stage 2- active labour, from complete cervical dilation to delivery of the newborn
Stage 3- from delivery of the fetus to expulsion of the placenta and final uterine contraction
Slide 30
What are the 3 major effects of prostaglandins?
- Prostaglandins stim contraction of uterine smooth muscle
- PGF2α potentiates the contractions induced by oxytocin by promoting formation of gap junctions between uterine smooth muscle cells
- Prostaglandins induce softening, dilation, and thinning out of the cervix, which occurs early during labour
Prostaglandins are used to induce labour and delivery
Slide 32
What is oxytocin’s role in pregnancy?
What increases # of oxytocin receptors?
Oxytocin binds to Gαq couple oxytocin receptors on membrane of uterine smooth muscle cells triggering PLC cascade, leads to Ca release, activates calmodulin, stims myosin light chain kinase to phosphorylate the regulatory light chain, causing contraction uterine smooth muscle and increase intrauterine pressure
Estrogen increases # of oxytocin receptors
Maternal oxytocin maintains labour (it releases in bursts once labour is initiated)
Slide 33
What is relaxin?
It’s effect on labour?
48 amino acid polypeptide hormone produced by corpus luteum, placenta, and decidua
Relaxin keeps the uterus in a quiet state during pregnancy
Production and release of relaxin increases during labour as it soften and thus help dilate cervix
What is lactation?
Breasts develop by estrogen and progesterone in puberty
During pregnancy gradual increases in levels of prolactin (PRL) and human chorionic somatomammotropin, also high levels of estrogens and progesterone lead to full developed breasts
Slide 35
What are the 4 hormones affecting breasts?
- Mammogenic- promotes proliferation of alveolar and duct cells
- Lactogenic- promotes initiation of milk production by alveolar cells
- Galactokinetic- promotes contraction of myoepithelial cells, milk ejection
- Galactopoietic- maintains milk production after it has been established
Slide 36
Slide 38
What is the composition of milk?
Milk is an emulsion of fats in an aqueous solution Contains sugar (lactose), proteins, cations (Na, K), and anions (Cl)
Cows milk has 3x more protein, higher electrolyte conc
Slide 37
What are the 4 effects of baby suckling?
- Stims sensory nerves that carry signal from breast to spinal cord where they synapse with neurons that carry signal to brain
- Afferent input from nipple inhibits neurons that release dopamine, this leads to increase prolactin release
- Afferent input from nipple triggers production and release of oxytocin
- Afferent input from nipple inhibits GnRH release, which inhibits FSH and LH
Slide 39
