Phys Chapter 82: Pregnancy and Lactation In the ovary, the ovum is a primary oocyte - - Just before it’s released by the follicle, its nucleus divides by meiosis to form a 1st polar body and a secondary oocyte o This causes each of the 23 pairs of chromosomes to lose one of its partners, which goes into the polar body o This leaves 23 unpaired chromosomes in the secondary oocyte The secondary oocyte is then ovulated with tons of granulosa cells attached to it, called the corona radiata The ovum is expelled into the peritoneal cavity, and must then enter one of the fallopian tubes and travel to the uterus - The inner surface of the fimbria of the fallopian tubes are lined with ciliated epithelium The cilia are activated by estrogen from the ovaries, causing them to beat toward the opening of the fallopian tube, called the ostium Fertilization of the ovum: - - - - - After the male ejaculates semen into the vagina, a few sperm are sent within 5-10 minutes from the vagina up through the uterus and fallopian tubes to the ampulla of the fallopian tubes o This is helped by contractions of the uterus and fallopian tubes stimulated by prostaglandins in the male seminal fluid, and also by oxytocin released from the posterior pituitary gland of the female during her orgasm o Of the many sperm that get deposited into the vagina, only a small % reach the ampulla Fertilization of the ovum usually happens in ampulla Before a sperm can enter the ovum, it has to first penetrate the many layers of granulosa cells attached to the outside of the ovum, called the corona radiata, and then penetrate the zona pellucida surrounding the ovum Once a sperm enters the ovum (currently a secondary oocyte), the oocyte divides again to from the mature ovum and a second polar body, which gets expelled o After this happens, the mature ovum still has 23 chromosomes in it’s female pronucleus One of these will be the X chromosome At the same time, the male sperm head swells into a male pronucleus The 23 unpaired chromosomes of the male pronucleus and the 23 unpaired chromosomes of the female pronucleus then align themselves to form a new set of 23 pairs, giving you 46 chromosomes total, in the fertilized ovum – page 1004 is a pic When a sperm forms, half of them will have an X chromosome, and half will have a Y o So if an x carrying sperm fertilizes the ovum, you get an XX girl o If a Y carrying sperm fertilizes the ovum, you get an XY boy After fertilization, the fertilized ovum spends 3-5 days going through the rest of the fallopian tube into the uterine cavity - - This is helped by epithelial secretions and cilia on the epithelium, which always beats toward the uterus, and weak contractions of the fallopian tube The isthmus of the fallopian tube is the last part of it before you get to the uterus o The isthmus remains contracted for the first 3 days after ovulation o Once the progesterone made by the ovum increases enough, it increases the # of progesterone receptors on the fallopian tube smooth muscle, and then activates receptors to relax the muscle and allow entry of the ovum into the uterus The time it takes to get to the uterus allows for the ovum to divide enough times to become a blastocyst, which is the stage it’s in when it enters the uterus The fallopian tube secretes lots of secretions to be nutrition for the developing blastocyst After reaching the uterus, the developing blastocyst usually remains in the uterine cavity for another 13 days before it implants in the endometrium - - So implantation is at about the 5th-7th day after ovulation – pic page 1005 Before implantation, the blastocyst gets its nutrition from uterine endometrial secretions, called “uterine milk” Implantation happens from trophoblast cells that develop over the surface of the blastocyst o Trophoblast secrete proteolytic enzymes to digest and liquefy the cells of the uterine endometrium o Some of the fluid and nutrients released are transported by the trophoblast into the blastocyst Once implantation happens, trophoblast and nearby cells of both the fetus and mom proliferate rapidly to form the placenta and other membranes of pregnancy Early nutrition of the embryo: - - - Progesterone secreted from the ovarian corpus luteum causes the uterine endometrium to convert it’s stromal cells into large swollen cells filled with glycogen, proteins, and lipids, for the development of the fetus When the embryo implants in the endometrium, the continued secretion of progesterone causes the endometrial cells to swell more and store even more nutrients o At this point, these cells are called decidual cells, and the total mass of cells is called the decidua As the trohpoblast cells invade the decidua, they digest it and release stored nutrients that the embryo uses o During the 1st week of development, this this the only way the embryo gets nutrients o The embryo will continue to get nutrition this way for up to 8 weeks, but by the 16th day, the placenta starts to provide nutrition too - - - - While the trophoblast cords from the blastocyst are attaching to the uterus, blood capillaries grow into the cords from the embryo’s forming vascular system o At about 21 days, the embryo’s heart can start pumping blood At the same time, blood sinuses from mom develop around the outsides of the trophoblastic cords The trophoblast then keeps sending out more and more projections, which become placental villi that the fetal capillaries grow into So the villi carry fetal blood, and are surrounded by sinuses that have mom’s blood The final placenta will have fetal blood flow through 2 umbilical arteries, then into the capillaries of the villi, and then back through an umbilical vein into the fetus – page 1006 o At the same time, mom’s blood flows from her uterine arteries into large maternal sinuses that surround the villi, and then back into uterine veins of the mother o Nutrients pass through the placental membrane by diffusion, just like in alveoli The major job of the placenta is to provide for diffusion of nutrition and oxygen from mom into the fetus’s blood, and diffusion of excretory stuff from the fetus back into mom In the early months of pregnancy, the placental membrane is still thick because it hasn’t fully developed, so it’s permeability is low o It also has a low surface area because it hasn’t grown enough yet o Because of all this, there isn’t much diffusion at first Later in pregnancy, the permeability increases because the placental membrane thins and the surface area increases, so there’s more diffusion Rarely, a break can happen in the placental membrane, which allows fetal blood cells to pass into mom Diffusion through the placenta: - - Oxygen in the blood of the maternal sinuses passes into fetal blood through simple diffusion, driven by an oxygen pressure gradient from moms blood to the fetus’s The fetal Po2 is only about 30 mm Hg, compared to mom’s 50 Po2 in the maternal sinuses o 3 reasons why this low Po2 is still enough to supply the tissues: The fetus Hgb is mainly fetal hemoglobin made by the fetus Fetal Hgb can carry up to 50% more oxygen than mom Hgb can The Hgb concentration of the fetal blood is about 50% higher than in the mom Bohr effect – Hgb can carry more oxygen at a low Pco2 than it can at a high Pco2 Fetal blood going to the placenta carries CO2 that is then sent to mom o All these changes cause the ability of the fetal blood to combine with oxygen to increase, and mom’s ability to bind the oxygen to decrease This will force even more oxygen from mom blood, and promote more oxygen uptake in the fetus This is called a double Bohr effect The fetus can only get rid of its carbon dioxide by sending it through the placenta to mom o - - The Pco2 of the fetal blood is slightly higher than mom’s blood, which causes diffusion of carbon dioxide into mom In late pregnancy, the fetus can use as much glucose as mom’s whole body does o To provide enough glucose, the trophoblast cells lining the placental villi can do facilitated diffusion of glucose through the placental membrane with carrier molecules Fetal wastes are also sent through the placenta to mom, and excreted with her wastes Hormones of pregnancy: - - In pregnancy, the placenta forms lots of human chorionic gonadotropin (hCG), estrogens, progesterone, and human chorionic somatommatropin hCG causes persistence of the corpus luteum, and prevents menstruation o Syncytial trophoblast cells secrete hCG into mom’s fluids o hCG can first be measured in the blood 8-9 days after ovulation, shortly before implantation The rate of hCG secretion then increases rapidly to max out at 10-12 weeks of pregnancy, and then decreases to a lower amount by 16-20 weeks, and stays at that level for the rest of the pregnancy o hCG is a glycoprotein that is very similar to LH o The most important job of hCG is to prevent the corpus luteum from involuting at the end of the female sexual cycle The corpus luteum then instead secretes even more sex hormones for the next few months, which prevent menstruation and cause the endometrium to continue to grow and store lots of nutrients This forms decidual cells, which are swollen with nutrition and ready for implantation The corpus luteum keeps secreting the sex hormones to keep the endometrium deciduous, which is needed for the early development of the fetus If the corpus luteum is removed before the 7th week of pregnancy, you almost always have an abortion After 7 weeks, the placenta secretes enough progesterone and estrogens to maintain pregnancy The corpus luteum involutes slowly after the 13th-17th week o hCG also stimulates the interstitial cells of the fetal testes to make testosterone, allowing for male sex organs to grow for a boy instead of female At the end of pregnancy, the test also causes the testes to descend into the scrotum The syncytial trophoblast cells of the placenta also secrete estrogen and progesterone o The estrogens in the placenta are not made at the placenta as cholesterol to estrogen o Instead, the placenta uses DHEA and 16-hydroxy-DHEA from mom and the fetus’s adrenals to make estrogen - - The baby’s adrenals are big and mostly made of a fetal zone that secretes tons of DHEA o In pregnancy, estrogens enlarge mom’s uterus, breasts, breast ducts, and external genitalia, and also relax mom’s pelvic ligaments o Effects of progesterone in pregnancy: Progesterone causes the decidual cells to develop Progesterone decreases the contractility of the pregnant uterus – prevents abortion Progesterone triggers mom’s fallopian tubes before implantation to secrete things and tells the uterus get nutrition ready Progesterone helps estrogen prepare mom’s breasts for lactation Human chorionic somatomammotropin – similar to GH, it decreases insulin sensitivity and makes glucose less available to mom, allowing more to be there for the baby o Glucose is the major substrate the baby uses to grow o It also promotes fatty acid movement into mom’s blood, so she can use that for energy The corpus luteum and the placenta also release relaxin, which relaxes pubic ligaments o This is increased by hCG Hormone changes in mom from pregnancy: o The anterior pituitary enlarges a lot during pregnancy and increases release of ACTH, TSH, and prolactin, while very little FSH and LH are released thanks to all the sex steroids o Glucorticoid release is increased in pregnancy o Aldosterone is released in pregnancy, causing water retention and possible pregnancyinduced hypertension o The thyroid enlarges during pregnancy and releases more thyroxine, thanks to hCG o The parathyroids enlarge in pregnancy, causing calcium reabsorption from mom’s bones to maintain blood calcium and provide it for the baby to ossify it’s own bones This is even more pronounced during lactation when the baby needs even more calcium than the fetus did How mom’s body responds in pregnancy: - - Mom’s sex organs get a lot bigger in pregnancy o Uterus gets bigger, breasts get bigger, vagina enlarges, the introitus widens All the sex steroids in pregnancy can also give the woman edema, acne, or masculine features The average weight gain during pregnancy is about 25-35 lbs, with most of this happening in the last 2 trimesters o This includes the baby, enlarged sex organs (so far about half), extra fluid in blood, & fat accumulation o After birth, the extra fluid is excreted, since the fluid retaining hormones are gone with the placenta During pregnancy, mom gets very hungry, due to the baby stealing her food & all the hormones - - - - - - Because of the all the increased metabolic hormones, mom’s metabolism increases in pregnancy o This makes her feel overheated o Mom also expends more energy than normal because of the extra weight she’s carrying By far the greatest amount of fetal growth happens in the last trimester of pregnancy o Normally, the mom doesn’t absorb enough protein, calcium, phosphates, and iron from her diet at this time to supply for these extra needs of the fetus o In preparation for this though, mom has been storing nutrients up to this point that the fetus can use To form the baby’s blood, it needs a lot of iron o So if mom doesn’t take in enough iron, it can cause a hypochromic anemia Mom also needs enough vitamin D to absorb enough calcium from the GI Often leading up to birth, you give a mom vitamin K, so that the baby can clot enough to handle birth Blood flow through the placenta, and the increase in mom’s metabolism, will increase mom’s cardiac output during pregnancy up to the 27th week o In the last 8 weeks, the cardiac output falls to a little above normal, for reasons we don’t know Mom’s blood volume increases during pregnancy, mainly during the second half of pregnancy o This is due to increased aldosterone and estrogen causing fluid retention, and the bone marrow making more RBCs o This provides a safety factor for bleeding during birth Because of mom’s increased metabolic rate and her larger size, mom uses more oxygen during pregnancy and forms more carbon dioxide, causing increased respiration and respiratory rate to keep up o This is helped by progesterone, and the baby pushing up on the diaphragm, which decreases ability to breathe deep Mom’s increased fluid intake and more accumulation of wastes makes her form more urine Also, the renal tubules ability to reabsorb sodium, chloride, and water is increased o Due to all the hormones made to increase reabsorption of salt and water In pregnancy, the renal vessels vasodilate for reasons we don’t know, causing an increased glomerular filtration rate Most of the fluid in the amniotic fluid is formed by the fetus’s urine About 5% of pregnant women have a rapid rise in blood pressure in the last few months, along with protein leaking into the urine, which is called preeclampsia o Symptoms of preeclampsia are excess salt and water retention, weight gain, edema, and hypertension o Renal blood flow and glomerular filtration rate will be decreased in preeclampsia o In preeclampsia, there’s failure of the placenta trophoblasts to invade the arterioles of the uterine endometrium and turn them into large blood vessels with low resistance This causes insufficient blood to the placenta, causing it to release things that cause a lot of the problems seen in preeclampsia, o Ecclampsia happens when there’s seizures, possible coma, greatly decreased urine output, liver malfunction, and extreme hypertension It usually happens shortly before birth, and results in a lot of deaths if they’re not treated If you treat quickly with vasodilators and C-section, few die from ecclampsia Parturition – birth of the baby - - - Towards the end of pregnancy, the uterus gets progressively more excitable, until finally the rhythmic contractions are strong enough to expel the baby o Progesterone inhibits uterine contractility during pregnancy, while estrogens increase uterine contractility More estrogen is secreted after the 7th month o Oxytocin causes uterine contractility Later in pregnancy, uterine muscle makes more receptors for oxytocin More oxytocin is released by the posterior pituitary at labor o Stretching a smooth muscle organ, like the uterus, will increase its contractility Stretch of the cervix is especially important During most of the months of pregnancy, the uterus has periodic episodes of weak and slow rhythmic contractions called Braxton Hicks contractions o These get progressively stronger toward the end of pregnancy, but then get suddenly exceptionally strong o This surge in contractions starts stretching the cervix and later forces the baby through the birth canal o These stronger contractions are called labor contractions o The positive feedback theory says these contractions get this strong when stretching of the cervix by the fetuses head finally becomes enough to elicit a strong reflex increase in contractility of the uterine body This pushes the baby forward, which stretches the cervix more and initiates more positive feedback ot the uterine body This process repeats until the baby is expelled So the more the cervix is stretched, the more contractile the uterus gets Also, stretching the cervix causes release of oxytocin Once uterine contractions get strong enough in labor, pain signals cause reflexes in the spinal cord to the abdominal muscles to intensely contract, helping to birth the baby The uterine contractions during labor start mainly at the top of the uterine fundus, and spread down over the body of the uterus o The intensity of contraction is great at the top and body of the uterus, but weak in the lower uterus and cervix o So each uterine contraction forces the baby downward towards the cervix o In the early part of labor, contractions may happen once every 30 minutes o - - - As labor progresses, the contractions show up as often as every few minutes, and the intensity increases a lot, with only a short period of relaxation in between If uterine contraction was more constant instead of rhythmic, like what happens from excess oxytocin, it blocks blood flow and kills the fetus In more than 95% of births, the head is the first part of the baby expelled o If not the head, it’s probably going to be the butt or feet, called breech presentation o The head acts as a wedge to open the birth canal as the fetus is forced downward o The first hurdle in the birth path is the cervix In the first stage of labor, the cervix progressively stretches and dilates, until the cervical opening is as wide as the head The first stage of labor can last from 8-24 hours in the 1st pregnancy, but can take just minutes in later pregnancies o Once the cervix has fully dilated, the fetal membranes rupture and the amniotic fluid is lost suddenly through the vagina o This starts the 2nd stage, where the baby’s head moves quickly into the birth canal leading to delivery This doesn’t take anywhere near as long as the first stage For up to 45 minutes after the baby is born, the uterus continues to contract to a smaller and smaller size, which shears off the placenta from the uterine wall, causing bleeding o Bleeding is limited cause the uterine smooth muscle arranged itself in a way during pregnancy where contractions aroundthese bleeding vessels will constrict them Cramping pains up to the first stage of labor are from hypoxia of the uterine muscles from blood vessel compression Labor pains in the second stage of labor are way more severe from all the stretching and tearing For a month after birth, the uterus involutes and gets smaller - Gets to half its pregnancy weight within a week Lactation suppresses pituitary gonadotropes, which will make the uterus get smaller quicker For 10 days after pregnancy, the uterine changes also lead to vaginal discharge called “lochia,” which starts bloody, and then gets clear After 10 days, the uterus has re-epithelialized, and is ready for normal non pregnant function again The breasts begin to develop at puberty – page 1014 pic of what’s in a breast - - This is stimulated by estrogens from the menstrual cycle, which stimulate growth of the breast mammary glands and deposition of fat to give the breasts mass The large amounts of estrogen in pregnancy from the placenta cause the breast duct system to grow and branch o At the same time, the breast stroma increases, and more fat is laid down in the stroma Final development of the breasts into a milk-secreting organ needs progesterone o - - - - Once the ducts develop, progesterone works with other hormones to cause the breast lobules to grow, along with budding of the alveoli and development of secretory changes in the alveoli Although estrogen and progesterone are needed for the physical development of the breast during pregnancy, they also inhibit actual secretion of milk The job of prolactin is to cause milk secretion o Prolactin from the anterior pituitary starts to increase at the 5th week of pregnancy up until birth o Despite this, in the first few days after birth, mom can’t lactate much because estrogen and progesterone still inhibit it o The fluid secreted in the last few days before, and the first few days after birth, is called colostrum It’s the same as milk, but without fat o After birth, the sudden loss of estrogen and progesterone from the placenta allows lactation by prolactin, and over the next week the breasts start releasing more milk and less colostrum o Secretion of milk needs GH, cortisol, parathyroid hormone, and insulin, to provide the amino acids, fatty acids, glucose, and calcium to make milk o Over the next few weeks after birth, prolactin levels decrease back to normal levels o Each time mom nurses the baby though, nervous signals from the nipples to the hypothalamus cause a surge in prolactin that lasts for an hour This keeps moms mammary glands secreting milk into the alveoli during that period of nursing While nursing, the ovarian cycle for ovulation won’t start again until a few weeks after you stop nursing o The same signals that suckling causes to go to the hypothalamus and release prolactin, will also inhibit release of FSH and LH o After a few months though, the pituitary progressively secretes more gonadotropes Milk is secreted continuously into the alveoli of the breasts, but doesn’t flow easily from the alveoli into the duct system, so it doesn’t leak, and instead needs ejected from the alveoli o When the baby suckles, it gets no milk at first o Suckling sends impulses to the spinal cord and then hypothalamus to cause release of oxytocin with prolactin o Oxytocin is then carried through blood to the breast, where it causes myoepithelial cells around the alveoli to contract, which ejects the milk into the ducts o This is called milk ejection aka milk-letdown o Many neural things can interfere with oxytocin release Nursing drains mom of energy