Week 4- Pregnancy and Human Development PDF

Pregnancy and Human Development Learning outcome • Describe the importance of sperm capacitation. • Explain the mechanisms behind the blocks to polyspermy. • Define fertilization. Embryonic development begins as the zygote undergoes cleavage • Describe the process and product of cleavage. • Descr...

Pregnancy and Human Development Learning outcome • Describe the importance of sperm capacitation. • Explain the mechanisms behind the blocks to polyspermy. • Define fertilization. Embryonic development begins as the zygote undergoes cleavage • Describe the process and product of cleavage. • Describe implantation. • Describe placenta formation, and list placental functions. • Which portion of the trophoblast accomplishes implantation? • What is the composition of the chorion? • What endometrial decidua cooperates with the chorionic villi to form the placenta? • Embryonic events include gastrula formation and tissue differentiation, which are followed by rapid growth of the fetus. Organogenesis: Differentiation of the Germ Layers • Describe functional changes in maternal reproductive organs and in the cardiovascular, respiratory, and urinary systems during pregnancy and indicate the effects of pregnancy on maternal metabolism and posture. • Explain how labor is initiated, and describe the three stages of labor. Some terms • Conceptus: the pregnant woman's developing offspring (embryo or fetus). • Pregnancy: The state of carrying a developing conceptus. • Gestation period: The time during which the development of the conceptus occurs. By convention, this extends from the last menstrual period until birth, approximately 280 days. • Fertilization occurs when a sperm's chromosomes combine with those of an egg to form a fertilized egg, or zygote the first cell of the new individual. • From fertilization through week 8, the embryonic period, the conceptus is called an embryo, and from week 9 through birth, the fetal period, the conceptus is called a fetus Size of the conceptus up to the early fetal stage. Embryos and fetus are shown approximately life size. (Measurements are crown-to-rump length.) Fertilization is most likely to occur within 24 to 48 hours after ejaculation. Consequently, for successful fertilization to occur, intercourse must occur no more than two days before ovulation and no later than 24 hours after, at which point the oocyte has traveled approximately one-third of the way down the uterine tube. Male and Female Reproductive System Fertilization • Male expels millions of sperm into his partner's vagina. Despite these vast numbers, most sperm don't reach the oocyte, even though it is only about 12 cm (5 inches) away. Millions of sperm leak from the vagina almost immediately. Of those remaining, millions more are destroyed by the vagina's acidic environment. Only a small fraction of sperm make it through the cervix and gain access to the uterus. • Sperm that do reach the uterus, propelled by their whiplike tail movements, are subjected to forceful uterine contractions that tumble them throughout the uterine cavity, where thousands more are destroyed by resident phagocytes. • Only a few thousand sperms, out of the millions in the male ejaculate, are conducted by reverse peristalsis into the uterine tube, where the oocyte may be moving leisurely toward the uterus. • They must first undergo capacitation, a biochemically delicate process that can take 2 to 10 hours. Specifically, the sperms motility must be enhanced and their membranes must become fragile so that the hydrolytic enzymes in their acrosomes can be released. • Sperm have receptors that sense the direction of fluid flow, temperature, and certain chemicals. Fertilization • The ovulated oocyte is encapsulated by the corona radiata and by the deeper zona pellucida • Central to this process is the sperm's acrosomal reaction, the release of acrosomal enzymes. • Polyspermy (entry of several sperm into an egg) occurs in some animals, but in humans only one sperm is allowed to penetrate the oocyte, ensuring monospermy, the one-sperm-peroocyte condition. In the rare cases of polyspermy that do occur, the embryos contain too much genetic material and die because they cannot successfully complete mitosis. • At least two mechanisms help ensure monospermy: the oocyte membrane block and the cortical reaction. • When a sperm binds to the oocyte's sperm-binding membrane receptors, it triggers the oocyte membrane block . • Once the plasma membranes of the sperm and oocyte have fused, waves of Ca2+ are released from the oocyte's endoplasmic reticulum into its cytoplasm. These calcium surges trigger the cortical reaction. • As the sperms cytoplasmic contents enter the oocyte, the sperm loses its plasma membrane. The centrosome from its midpiece assembles microtubules which the sperm uses to propel its DNA-rich nucleus toward the oocyte nucleus. • On the way, its nucleus swells to about five times its previous size to form the male pronucleus. Meanwhile the secondary oocyte is activated from its semidormant state by the same calcium surges that trigger the cortical reaction. • Following the fluctuations in calcium levels, a shower of zinc ions bursts from the egg. This efflux of zinc allows the oocyte to complete meiosis II, forming the ovum nucleus and the second polar body. • This accomplished, the ovum nucleus swells, becoming the female pronucleus, and the two pronuclei replicate their DNA as they approach each other. As a mitotic spindle develops between them, the pronuclei membranes rupture, releasing their chromosomes together into the immediate vicinity of the newly formed spindle. The true moment of fertilization occurs as the maternal and paternal chromosomes combine and produce the diploid zygote, or fertilized egg. • The zygote, the first cell of a new individual, is now ready to undergo the first mitotic division of the conceptus. Cleavage is a period of fairly rapid mitotic divisions of the zygote without intervening growth. Some 36 hours after fertilization, the first cleavage division of the zygote has produced two identical cells (called blastomeres). These divide to produce four cells, then eight, and so on. By 72 hours after fertilization, a loose collection of cells that form a berry-shaped cluster of 16 or more cells called the morula has been formed. By day 4 or 5 after fertilization, the embryo consists of about 100 cells. It floats free in the uterus and has begun accumulating fluid within an internal cavity. The zona pellucida starts to break down and the inner structure, now called a blastocyst, "hatches" from it. The blastocyst • The blastocyst is a fluid-filled hollow sphere composed of a single layer of large, flattened cells called trophoblast cells and a small cluster of 20 to 30 rounded cells, called the embryoblast (or inner cell mass), • The trophoblast has several key roles during development: 1. Trophoblast cells play an important role in implanting the embryo in the wall of the uterus. 2. As suggested by the literal translation of trophoblast ("nourishment generator"), it makes a major contribution to the chorion, the embryo's portion of the placenta. 3. It protects the conceptus from attack by the mother's immune cells by producing several factors with immunosuppressive effects. • The embryoblast becomes the two-layered embryonic disc, which forms the embryo proper and the extraembryonic membranes. Implantation • Implantation While the blastocyst floats in the uterine cavity for two to three days, it is nourished by the glycoprotein-rich uterine secretions. Then, six to seven days after ovulation, implantation begins. The receptivity of the endometrium to implantation-the so-called window of implantation-is opened by the surging levels of ovarian hormones (estrogens and progesterone) in the blood • If the mucosa is receptive, cell adhesion molecules bind the trophoblast to the endometrial epithelium, and the blastocyst implants high in the uterus. If the endometrium is not yet optimally mature, the blastocyst fails to attach and drifts to a lower level, implanting when it finds a site with the proper receptors and chemical signals. • The trophoblast cells overlying the embryoblast adhere to the endometrium and secrete digestive enzymes and growth factors onto the endometrial surface. • The endometrium quickly thickens at the point of contact and takes on characteristics of an acute inflammatory response-the uterine blood vessels become more permeable and leaky, and inflammatory cells including lymphocytes, natural killer cells, and macrophages invade the area. The trophoblast then proliferates and forms two distinct layers: • The Cytotrophoblast forms the innermost layer of cells. • The Syncytiotrophoblast forms the outermost layer. Here the cells have fused together to form a single multinuclear cytoplasmic mass, or syncytium. • This syncytium sends out long protrusions that invade the endometrium and rapidly digest the uterine cells it contacts. As the endometrium is eroded, the blastocyst burrows into this thick, velvety lining and is surrounded by a pool of blood leaked from degraded endometrial blood vessels. • • Proliferation of the endometrial cells then covers and seals off the implanted blastocyst from the uterine cavity. In cases where implantation fails to occur, a receptive uterus becomes nonreceptive once again. At least twothirds of all zygotes formed fail to implant by the end of the first week or spontaneously terminate • Moreover, about 30% of implanted embryos later miscarry due to genetic defects of the embryo, uterine malformation, or other problems. • Successful implantation takes about five days. It is usually completed by day 12, which is day 26 of a woman's menstrual cycle-just before the endometrium normally begins to slough off. • Menstruation would flush away the newly implanted embryo, so the embryo takes steps to prevent this by rescuing the corpus luteum. • How does the embryo rescue the corpus luteum? Its syncytiotrophoblast secretes human chorionic gonadotropin (hCG) which acts like LH but bypasses the usual hypothalamus-pituitary-ovarian controls. • Just like LH, hCG prompts the corpus luteum to continue secreting Progesterone and Estrogens. • The syncytiotrophoblast, which becomes part of the chorion (a major part of the embryo's contribution to the placenta) continues to make hCG throughout pregnancy. • hCG also helps prevent the mother's immune system from rejecting the implanted embryo. All pregnancy tests used today are antibody tests that detect hCG in a woman's blood or urine. Implantation • Between the second and third month, the placenta assumes the role of progesterone and estrogen production for the remainder of the pregnancy. • The corpus luteum then degenerates and the ovaries remain inactive until after birth. • Initially, the implanted embryo acts like a parasite that obtains its nutrition by digesting the endometrial cells. • By the second month, the placenta is providing nutrients and oxygen to the embryo and carrying away embryonic metabolic wastes. Formation of the Placenta Formation of the placenta is called placentation, the placenta is a pancakeshaped temporary organ that originates from both embryonic and maternal tissues. Cells from the original embryoblast give rise to a layer of extraembryonic mesoderm that lines the inner surface of the trophoblast Together these become the chorion. The chorion develops fingerlike chorionic villi, which become especially elaborate where they are in contact with maternal blood Soon the mesodermal cores of the chorionic villi are invaded by newly forming blood vessels, which extend to the embryo as the umbilical arteries and vein. The continuing erosion of the endometrium produces large, blood-filled lacunae, or intervillous spaces, in the functional layer of the endometrium The villi come to lie in these spaces totally immersed in maternal blood. The part of the endometrium that lies beneath the embryo becomes the Decidua Basalis and that surrounding the uterine cavity face of the implanted embryo forms the Decidua Capsularis Together, the chorionic villi and the decidua basalis form the disc-shaped placenta. Formation of the Placenta The placenta detaches and sloughs off after the infant is born, so the name of the maternal portion-decidua ("that which falls off")-is appropriate. During development, the decidua capsularis expands to accommodate the fetus, which eventually fills and stretches the uterine cavity. As the developing fetus grows, the villi in the decidua capsularis are compressed and degenerate, while those in the decidua basalis increase in number and branch even more profusely. The placenta is usually fully functional as a nutritive, respiratory, excretory, and endocrine organ by the end of the third month of pregnancy. However, well before this time, oxygen and nutrients are diffusing from maternal to embryonic blood, and embryonic metabolic wastes are passing in the opposite direction. The barriers to free passage of substances between the two blood supplies are embryonic barriers-the membranes of the chorionic villi and the endothelium of embryonic capillaries. Although the maternal and embryonic blood supplies are very close, they normally DO NOT INTERMIX Detailed anatomy of the vascular relationships in the mature decidua basalis. This state of development has been accomplished by the end of the third month of development. Formation of the Placenta • The placenta secretes hCG from the beginning, but the ability of its syncytiotrophoblast cells to produce the estrogens and progesterone of pregnancy matures much more slowly. • If, for some reason, placental hormones are inadequate when hCG levels diminish, the endometrium degenerates and the pregnancy spontaneously aborts. • Throughout pregnancy, blood levels of estrogens and progesterone continue to increase. They encourage growth and further differentiation of the mammary glands and ready them for lactation. • The placenta also produces other hormones, such as human placental lactogen and relaxin. Embryonic events include gastrula formation and tissue differentiation, which are followed by rapid growth of the fetus • Even while implantation is occurring, the blastocyst is being converted to a Gastrula, in which the three primary germ layers form, and the extraernbryonic membranes develop. The embryoblast first subdivides into two layers-the upper Epiblast and the lower Hypoblast. The subdivided embryoblast is now called the Embryonic Disc • The extraembryonic membranes: that form during the first two to three weeks of development include the amnion, yolk sac, allantois, and chorion • The amnion develops when cells of the epiblast fashion themselves into a transparent membranous sac. This sac surrounds the amniotic cavity, which is filled with amniotic fluid. • eventually, the amnion extends all the way around the embryo, broken only by the umbilical cord "bag of waters" Embryonic events include gastrula formation and tissue differentiation, which are followed by rapid growth of the fetus • The amnion provides a floating environment that protects the developing embryo against physical trauma, and helps maintain a constant temperature. • The fluid also prevents the rapidly growing embryonic parts from adhering and fusing together and allows the embryo considerable freedom of movement. • Initially, the fluid is derived from the maternal blood, but as the fetal kidneys become functional later in development, fetal urine contributes to amniotic fluid volume. • The yolk sac forms from cells of the primitive gut, which arrange themselves into a sac that hangs from the ventral surface of the embryo. • The amnion and yolk sac resemble two balloons touching one another with the Embryonic Disc at the point of contact. In many species, in humans it contains very little yolk and has a nutritive function only during the second and third weeks. Embryonic events include gastrula formation and tissue differentiation, which are followed by rapid growth of the fetus Why the yolk sac is important in humans because it: • Forms part of the gut ( digestive tube) • ls the source of the earliest blood cells • Is the location from which primordial germ cells migrate to the gonads to form sperm and ova The Allantois forms as a small outpocketing of embryonic tissue at the caudal end of the yolk sac. In humans, the allantois is the structural base for the umbilical cord that links the embryo to the placenta, and ultimately it becomes part of the urinary bladder. The fully formed umbilical cord contains a core of embryonic connective tissue, the umbilical arteries and vein, and is covered externally by amniotic membrane. Gastrulation: Germ Layer Formation • During week 3, the two-layered embryonic disc transforms into a three-layered embryo in which the primary germ layers: Ectoderm, Mesoderm, and Endoderm. • This process, called Gastrulation: involves cellular rearrangements and migrations. • Gastrulation begins when a groove with raised edges called The Primitive Streak appears on the dorsal surface of the embryonic disc. • This groove establishes the longitudinal axis of the embryo. Surface (epiblast) cells of the embryonic disc then migrate medially and enter the primitive streak. • The first cells to enter the groove displace the hypoblast cells of the yolk sac and form the most inferior germ layer, the Endoderm. • Those that follow push laterally between the cells at the upper and lower surfaces, forming the Mesoderm. As soon as the mesoderm is formed, the mesodermal cells immediately beneath the early primitive streak aggregate, forming a rod of mesodermal cells called the Notochord. (the first axial support of the embryo) • The cells that remain on the embryo's dorsal surface are the Ectoderm. Formation of the three primary germ layers. The three primary germ layers serve as the primitive tissues from which all body organs derive. • Ectoderm ("outer skin") fashions structures of the nervous system and the skin epidermis. • Endoderm ("inner skin") forms the epithelial linings of the digestive, respiratory, and urogenital systems, and associated glands. • Mesoderm ("middle skin") forms virtually everything else. ***Both ectoderm and endoderm consist mostly of cells that are securely joined to each other and are epithelia. Mesoderm, by contrast, is a Mesenchyme (free cells are able to migrate widely within the embryo) Organogenesis: Differentiation of the Germ Layers Formation of body organs and organ systems. It is amazing how much organogenesis occurs in such a short time in such a small amount of living matter. Specialization of t he Endoderm • The tube of endoderm formed by the folding process is called the Primitive Gut. It becomes the epithelial lining of the gastrointestinal tract. • The organs of the GI tract (pharynx, esophagus, etc.) quickly become apparent, and then the oral and anal ends of the gut open. • The mucosa lining of the respiratory tract forms as an outpocketing of the foregut. • The glands arise as endodermal outpocketings at various points farther along the tract. *** For example, the epithelium of the thyroid, parathyroid, and thymus forms from the pharyngeal endoderm Specialization of the Ectoderm • The first major event in organogenesis is Neurulation , the differentiation of ectoderm that produces the brain and spinal cord. • This process is induced by chemical signals from the Notochord, the rod of mesoderm • The ectoderm overlying the notochord thickens, forming the Neural Plate. • Then the ectoderm folds, forming the Neural Groove as well as neural folds on either side. • By day 22, the superior margins of the neural folds fuse, forming a Neural Tube, which soon pinches off from the ectodermal layer and becomes covered by surface ectoderm. The anterior part of Neural Tube become later the brain and the rest becomes the spinal cord. • The associated Neural Crest cells migrate widely and give rise to the cranial, spinal, and sympathetic ganglia (and associated nerves), to the chromaffin cells of the adrenal medulla and to pigment cells of the skin, and they contribute to some connective tissues. Specialization of the Mesoderm • The first evidence of mesodermal differentiation is the appearance of The Notochord in the embryonic disc. • The notochord is eventually replaced by the Vertebral Column, but its remnants persist in the springy Nucleus Pulposus of the Intervertebral Discs. • Shortly thereafter, three mesodermal aggregates develop on either side of the notochord. • The largest of these, the somites: are paired mesodermal blocks that hug the notochord on either side. • All of the pairs of somites are present by the end of week 5. • Flanking the Somites laterally are small clusters of segmented mesoderm called Intermediate Mesoderm and then double sheets of Lateral Plate Mesoderm. Specialization of the Mesoderm 1- Each Somite has three functional parts: Sclerotome, Dermatome, and Myotome: • Cells of the Sclerotome ("hard piece") migrate medially, gather around the notochord and neural tube, and produce the vertebra and rib at each associated level. • Dermatome ("skin piece") cells help form the dermis of the skin in the dorsal part of the body. • The Myotome ("muscle piece") cells develop in conjunction with the vertebrae. They form the skeletal muscles of the neck, body trunk, and, via their limb buds, the muscles of the limbs. 2- Cells of the Intermediate Mesoderm form the gonads and kidneys. 3- The lateral plate Mesoderm splits to form paired mesodermal layers: the Somatic Mesoderm and the more inferior Splanchnic Mesoderm • Cells of the Somatic Mesoderm help to form: • The skin dermis of the ventral body region • The parietal serosa that lines the ventral body cavity • Most tissues of the limbs • The Splanchnic Mesoderm form the heart and blood vessels and most connective tissues of the body, as well as nearly the entire wall of the digestive and respiratory organs. During pregnancy, the mother undergoes anatomical physiological, and metabolic changes • Anatomical Changes: • As pregnancy progresses, the female reproductive organs become increasingly vascular and engorged with blood, and the vagina develops a purplish hue (Chadwick's sign). Prodded by rising levels of estrogens and progesterone, • the breasts enlarge and engorge with blood, and their areolae darken. • Some women develop increased pigmentation of facial skin of the nose and cheeks, a condition called chloasma or the "mask of pregnancy.“ • The degree of uterine enlargement during pregnancy is remarkable. Starting as a fist-sized organ, the uterus fills most of the pelvic cavity by 16 weeks. The placenta is fully formed, uterine muscle is hypertrophied, and amniotic fluid volume is increasing. • As pregnancy continues, the uterus pushes higher into the abdominal cavity, exerting pressure on abdominal and pelvic organs • As birth nears, the uterus reaches the level of the sternum's xiphoid process and occupies most of the abdominal cavity. The crowded abdominal organs press superiorly against the diaphragm, which intrudes on the thoracic cavity. As a result, the ribs flare, causing the thorax to widen . • The increasing bulkiness of the anterior abdomen changes the woman's center of gravity, and many women develop Lordosis (accentuated lumbar curvature) and backaches during the last few months of pregnancy. • Relaxin, produced by the corpus luteum and placenta, causes pelvic ligaments and the pubic symphysis to relax, widen, and become more flexible. This increased flexibility eases passage of the baby during birth, but it may result in a waddling gait in the meantime. • Considerable weight gain occurs during a normal pregnancy. Because some women are over- or underweight before pregnancy begins, it is almost impossible to state the ideal or desirable weight gain. However, summing up the weight increases resulting from fetal and placental growth, increased size of the maternal reproductive organs and breasts, and greater blood volume during pregnancy, a weight gain of approximately 13 kg (about 28 lb) is fairly typical. • Good nutrition is necessary all through pregnancy if the developing fetus is to have all the building materials (especially proteins, calcium, and iron) needed to form its tissues. The B vitamin folic acid reduces the risk of having a baby with neural tube problems such as spina bifida and anencephaly Metabolic Changes • As the placenta enlarges, it secretes various hormones that influence the mother's metabolism. • Placental growth hormone suppresses and replaces the mother's growth hormone. It enhances nutrient availability to the fetus by stimulating lipolysis and glucose production (gluconeogenesis ). • Human placental lactogen (hPL) is secreted in amounts proportional to the placenta's size. In cooperation with estrogens and progesterone, it stimulates maturation of the breasts for lactation, promotes growth of the fetus, and exerts a glucose-sparing effect in the mother. This means that maternal cells metabolize more fatty acids and less glucose than usual, sparing glucose for use by the fetus. It also reduces insulin sensitivity. Consequently, gestational diabetes mellitus occurs. Over half of these women go on to develop type 2 diabetes later in life. • Corticotropin-releasing hormone (CRH) (levels rise dramatically toward the end of pregnancy. This rise is thought to be related to the timing of birth. As CRH levels rise, the mother's ACTH and cortisol levels rise, too. This may protect her in times of stress, such as giving birth. Rising cortisol levels in the fetus promote maturation, particularly of the lungs. • Plasma levels of activated vitamin D rise two- to threefold during pregnancy, which increases absorption of dietary calcium. This rise in vitamin D occurs in spite of levels of parathyroid hormone that are normal or even low when intake of calcium is adequate. This ensures that the developing fetus will have adequate calcium to mineralize its bones. Physiological Changes • Gastrointestinal System: The nausea and vomiting (commonly called morning sickness) suffered by many women during the first few months of pregnancy are believed to be related to elevated levels of hCG, estrogens, and progesterone. • Heartburn, due to reflux of stomach acid into the esophagus, is common because the esophagus is displaced and the stomach is crowded by the growing uterus. • Constipation occurs as the motility of the digestive tract decreases. • Urinary System: The kidneys produce more urine during pregnancy because of the mother's increased metabolic rate, greater blood volume, and the additional burden of disposing of fetal metabolic wastes. • As the growing uterus compresses the bladder, urination becomes more frequent, more urgent, and sometimes uncontrollable (stress incontinence). • Respiratory System: The nasal mucosa responds to estrogens by becoming edematous and congested. Thus, nasal stuffiness and occasional nosebleeds may occur. • Tidal volume (increases markedly during pregnancy) while respiratory rate is relatively unchanged and residual volume (decreases. The increase in tidal volume is due to the increased production of C02 enhancement of the sensitivity of the medullary respiratory center to C02 caused by progesterone. • Many women exhibit dyspnea or difficult breathing, during the later stages of pregnancy when the diaphragm is pushed superiorly by the increasing size of the uterus. Physiological Changes • Cardiovascular System: The most dramatic physiological changes occur in the cardiovascular system. Total body water rises, and blood volume may increase as much as 40% by the 32nd week to accommodate the additional needs of the fetus. • The rise in blood volume also safeguards against blood loss during birth. Mean blood pressure typically decreases during midpregnancy, but then rises to normal levels during the third trimester. • Cardiac output increases by 35-40% at various stages of pregnancy. This helps propel the greater circulatory volume around the body. • The uterus presses on the pelvic blood vessels, which may impair venous return from the lower limbs, resulting in varicose veins and leg edema • Interestingly, some fetal cells do make their way into the maternal circulation. Because these cells are undifferentiated, they can take up residence in various maternal tissues and differentiate into the types of cells that surround them. It is not clear what consequences this may have-they may predispose a woman to autoimmune diseases or they may protect her against certain diseases. The three stages of labor are the dilation, expulsion, and placental stages Parturition ("bringing forth young") is the conclusion of pregnancy-giving birth to the baby. It usually occurs within 15 days of the calculated due date (280 days from the last menstrual period). The series of events that expel the infant from the uterus are collectively called labor. Initiation of Labor • The fetus largely determines its own birth date, and several events and hormones interlock to trigger labor: • As the fetal hypothalamus and adrenal glands mature during the last few weeks of pregnancy, increased CRH from the fetal hypothalamus leads to increased fetal cortisol release. • Fetal cortisol then begins a positive feedback loop with placental CRH-cortisol. • Fetal cortisol triggers the final maturation of the Fetal Lungs, which increases the production and release of Surfactant Protein A (SP-A). SP-A, in turn, acts as an additional signal that the fetus is ready to be born. • The rapid increase in cortisol levels also causes a rapid increase in estrogen production by the placenta. • A major function of progesterone during pregnancy is to suppress contraction of uterine smooth muscle as it is stretched by the growing fetus. This calming action of progesterone is important for preventing preterm-labor. • As estrogen levels rise at the end of pregnancy, they switch the progesterone receptor to a less effective type. The increase in estrogens (together with the decrease in progesterone's action) has the following effects: • It prepares the cervix for dilation. Estrogens increase the synthesis of both prostaglandins (and their receptors. Prostaglandins play a major role in the thinning and softening of the cervix just before and during labor. • It prepares the myometrium of the uterus for contraction. Additional contractile machinery (including actin, myosin, and myosin light chain kinase) is synthesized so that the uterus can contract more forcefully. Like the heart, the uterus needs to contract as a unit. As the onset of labor nears, gap junctions are formed between myometrial cells to tie them together electrically. As a result, the myometrium becomes increasingly irritable. Weak, irregular uterine contractions begin to occur. These contractions, called Braxton Hicks contractions, have caused many women to go to the hospital, only to be told that they were in false labor and sent home. • It increases the sensitivity of t he myometrium to chemical messengers that cause it t o contract. Under the influence of rising estrogen action and decreasing progesterone action, the myometrial cells make abundant receptors for oxytocin and prostaglandin. These are the two chemical messengers that will drive myometrial contraction during true labor. As birth nears, the now powerful uterine muscle is highly sensitive to prostaglandins and oxytocin. Under the influence of estrogens, the placenta releases prostaglandins that trigger the rhythmic expulsive contractions of true labor. Pressure from the baby's head dilates the cervix. Increasing cervical distension activates the mother's hypothalamus, which signals for oxytocin release by the posterior pituitary. Several positive feedback mechanisms • involving prostaglandins and oxytocin are propelled into action-contractions and greater distension of the cervix cause the release of more prostaglandins and oxytocin, which cause greater contractile force, and so on. • Expulsion of the baby is aided by a chemical change in fetal fibronectin, the natural "stickum" (adhesive protein) that bound the fetal and maternal tissues of the placenta together up to this point in pregnancy. • Prostaglandins are essential for initiating labor in humans, and interfering with their production will hinder onset of labor. • For example, antiprostaglandin drugs such as ibuprofen can inhibit the early stages of labor and such drugs are used occasionally to prevent preterm births. Stages of Labor includes the Dilation, Expulsion, and Placental stages • Dilation stage: is the time from labor's onset until the cervix is fully dilated by the baby's head (about 10 cm in diameter). • As labor starts, weak but regular contractions begin in the upper part of the uterus and move toward the vagina. • At first, only the superior uterine muscle is active; contractions are 15-30 minutes apart, and last for 10-30 seconds. • As labor progresses, the contractions become more vigorous and rapid, and the lower part of the uterus gets involved. • As the infant's head is forced against the cervix with each contraction, the cervix softens, effaces (thins), and dilates. • Several events happen during this phase. Engagement occurs when the infant's head enters the true pelvis • As descent continues through the vagina (sometimes referred to as the birth canal), the baby's head rotates so that its greatest dimension is in the anteroposterior line • Eventually the amnion ruptures, releasing the amniotic fluid, an event commonly referred to as the mother's "water breaking." Engagement occurs when the infant's head enters the true pelvis. Stages of Labor • Expulsion stage. It lasts from full dilation to delivery of the infant, or actual childbirth. By the time the cervix is fully dilated, strong contractions occur every 2-3 minutes and last about 1 minute. • In this stage, a mother undergoing labor without local anesthesia has an increasing urge to push or bear down with the abdominal muscles. • Although this phase may last 2 hours, it is typically 50 minutes in a first birth and around 20 minutes in subsequent births. • Crowning occurs when the largest dimension of the baby's head distends the vulva. At this point, an episiotomy is sometimes done to reduce tissue tearing. • An episiotomy is an incision made to widen the vaginal orifice. The baby's neck extends as the head exits from the perineum, and once the head has been delivered, the rest of the baby's body is delivered much more easily. • After birth, the umbilical cord is clamped and cut. When the infant is in the usual vertex, or head-first, presentation, the skull (its largest diameter) acts as a wedge to dilate the cervix. • The head-first presentation also allows the baby to be suctioned free of mucus and to breathe even before it has completely exited from the birth canal. • ln breech (buttock-first), these advantages are lost and delivery is much more difficult, often requiring the use of forceps, or a C-section. Stages of Labor • Placental stage. Is the delivery of the placenta and its attached fetal membranes, collectively called the afterbirth, • Is usually accomplished within 30 minutes after birth of the infant. • The strong uterine contractions that continue after birth compress uterine blood vessels, limit bleeding, and shear the placenta off the uterine wall (cause placental detachment). • The blood vessels in the umbilical cord are counted after the placenta is delivered to verify the presence of two umbilical arteries and one umbilical vein because the absence of one umbilical artery is often associated with cardiovascular disorders in the newborn. An infant's extrauterine adjustments include taking the first breath and closure of vascular shunts • The neonatal period is the four-week period following birth. Here we will be concerned with the events of just the first few hours after birth in a normal infant. • Birth represents quite a shock to the infant. Exposed to physical trauma during the birth process, it is suddenly cast out of its watery, warm environment and its placental life supports are severed. • Now it must do for itself all that the mother had been doing for it-breathe, obtain nutrients, excrete, and maintain its body temperature. Two critical adjustments must occur. • Taking the first breath: The crucial first requirement is to breathe. Vasoconstriction of the umbilical arteries, initiated when they are stretched during birth, leads to loss of placental support. • Once CO2 is no longer removed by the placenta, it accumulates in the baby's blood, causing central acidosis. This excites respiratory control centers in the baby's brain and triggers the first inspiration. • The first breath requires a tremendous effort-the airways are tiny, and the lungs are collapsed. • However, once the lungs have been inflated in full-term babies, surfactant in alveolar fluid reduces surface tension in the alveoli, and breathing is easier. The rate of respiration is rapid (about 45 respirations/min) during the first two weeks and then gradually decreases. • Keeping the lungs inflated is much more difficult for premature infants, because surfactant production occurs during the last months of prenatal life. • Consequently, preemies are usually put on a ventilator until their lungs are mature enough to function on their own. Two critical adjustments must occur. • Occlusion of special fetal blood vessels and vascular shunts: • After birth the special umbilical blood vessels and fetal shunts are occluded • At 1 and 5 minutes after birth, the infant's physical status is assessed based on five signs: heart rate, respiration, color, muscle tone, and reflexes. • Each observation is given a score of 0 to 2, and the total is called the Apgar score. An Apgar score of 8 to 10 indicates a healthy baby. • Lower scores reveal problems in one or more of the physiological functions assessed. • For 6-8 hours after birth, infants pass through an unstable transitional period marked by alternating periods of increased activity and sleep. During the activity periods, vital signs are irregular and the baby gags frequently as it regurgitates mucus and debris. • After this, the infant stabilizes, with waking periods (dictated by hunger) occurring every 3-4 hours. Lactation is milk secretion by the mammary glands in response to prolactin • Lactation is production of milk by the hormone-prepared mammary glands. • Rising levels of (placental) estrogens, progesterone, and human placental lactogen toward the end of pregnancy stimulate the hypothalamus to release Prolactin Releasing Factors (PRFs). The anterior pituitary gland responds by secreting Prolactin. • During the initial delay (and during late gestation), the mammary glands secrete a yellowish fluid called Colostrum. • It has less lactose than milk and almost no fat, but it contains more protein, vitamin A, and minerals than true milk. Like milk, colostrum is rich in IgA antibodies. Since these antibodies are resistant to digestion in the stomach, they may help to protect the infant's digestive tract against bacterial infection. • After birth, prolactin release gradually decreases, and continued milk production depends on mechanical stimulation of the nipples, normally provided by the suckling infant. Mechanoreceptors in the nipple send action potentials to the hypothalamus, stimulating secretion of PRFs. This results in a burst-like release of prolactin, which stimulates milk production for the next feeding. • The same action potentials also prompt hypothalamic release of Oxytocin from the posterior pituitary via a positive feedback ,mechanism. Oxytocin causes the let-down reflex, the actual ejection of milk from the alveoli of the mammary glands. Let-down occurs when oxytocin binds to myoepithelial cells surrounding the glands, after which milk is ejected from both breasts, not just the suckled one. • Oxytocin also stimulates the recently emptied uterus to contract, helping it to return to (nearly) its pre-pregnant size. Breast milk has advantages for the infant: • Its fats and iron are better absorbed and its amino acids are metabolized more efficiently than those of cow's milk. • It has a host of beneficial chemicals, including IgA, complement, lysozyme, interferon, and lactoperoxidase, that protect infants from life-threatening infections. • Mother's milk also contains Interleukins and Prostaglandins that prevent overzealous inflammatory responses, • Glycoprotein that prevents the ulcer-causing bacterium (Helicobacter pylori) from attaching to the stomach mucosa. • It helps beneficial bacteria to colonize the infant's gut by providing certain oligosaccharides (sugars) they need to grow. • Its natural Laxative effect helps to cleanse the bowels of Meconium: a tarry green-black paste containing sloughed-off epithelial cells, bile, and other substances. • Since meconium, and later feces, provides the route for eliminating bilirubin from the body, clearing meconium as quickly as possible helps to prevent physiological jaundice. • When nursing is discontinued, the stimulus for prolactin release and milk production ends, and the mammary glands stop producing milk. • Women who nurse their infants for six months or more lose a significant amount of calcium from their bones, but those on sound diets usually replace lost bone calcium after weaning the infant. References and Further Reading • Elaine N. Marieb and Katja N. Hoehn (2019). Human Anatomy and Physiology. 11th Edition. Pearson Education. Chapter 28