Premed · Premed · Anatomy Physiology 2
Lecture 23: Pregnancy, Development, and Lactation
Anatomy and Physiology II
Learning Objectives
By the end of this lecture, students will be able to:
- Describe the events of fertilization and the mechanisms that prevent polyspermy
- Outline the stages of pre-embryonic development from zygote to implantation
- Describe the formation and functions of the placenta and extraembryonic membranes
- Summarize the major events of embryonic and fetal development by trimester
- Describe the hormonal changes during pregnancy and their physiological effects
- Explain the physiology of labor and delivery (parturition)
- Describe the hormonal regulation of lactation
Lecture Content
I. Fertilization
Fertilization occurs in the ampulla of the uterine tube, typically within 12-24 hours after ovulation. Before sperm can fertilize an oocyte, they must undergo two preparatory processes. Capacitation is a physiological maturation process taking approximately 7 hours in the female reproductive tract. It involves removal of cholesterol from the sperm plasma membrane (making it more fluid and permeable to calcium), removal of the glycoprotein coat and seminal plasma proteins, and the development of hyperactive flagellar movement. The acrosomal reaction is triggered when capacitated sperm contacts the corona radiata or zona pellucida, causing release of acrosomal enzymes (hyaluronidase and acrosin). Hyaluronidase disperses the corona radiata cells, while acrosin digests a pathway through the zona pellucida.
Steps of Fertilization
Fertilization proceeds through a defined sequence. The sperm first penetrates the corona radiata using hyaluronidase and flagellar movement. It then binds to ZP3 glycoprotein on the zona pellucida, triggering the acrosomal reaction and digestion through the zona pellucida by acrosin. Next, the sperm fuses with the oocyte plasma membrane, and the sperm nucleus enters the oocyte cytoplasm.
Two mechanisms prevent polyspermy (fertilization by more than one sperm). The fast block involves depolarization of the oocyte membrane through sodium influx, which transiently prevents additional sperm fusion for approximately one minute. The slow block (cortical reaction) involves cortical granules beneath the oocyte membrane releasing enzymes into the perivitelline space, causing the zona pellucida to harden (the zona reaction) and ZP3 receptors to be destroyed, providing a permanent block.
Following sperm entry, the secondary oocyte completes meiosis II, producing the ovum and second polar body. Male and female pronuclei form, migrate toward each other, their membranes break down, and the chromosomes combine on a mitotic spindle, creating the zygote (2n = 46).
II. Pre-Embryonic Development (Weeks 1-2)
Cleavage and Blastocyst Formation
Cleavage consists of rapid mitotic divisions of the zygote without overall growth, so cells become progressively smaller. The zygote progresses through 2-cell, 4-cell, 8-cell, and 16-cell stages, with the 16-cell stage forming a solid ball of cells called the morula. This occurs during transit through the uterine tube over approximately 3-4 days.
By day 5, the blastocyst forms as a hollow sphere with three distinct components. The trophoblast is the outer cell layer that will form the embryonic portion of the placenta and secrete hCG. The inner cell mass (embryoblast) is a cluster of cells at one pole that will form the embryo proper. The blastocoel (blastocyst cavity) is the fluid-filled central cavity. The blastocyst enters the uterine cavity around day 4-5 and floats freely for 1-2 days, nourished by uterine secretions.
Implantation
Implantation occurs approximately days 6-10 after fertilization, typically in the posterior wall of the uterine fundus. During this process, the trophoblast differentiates into two layers. The cytotrophoblast forms the inner layer of distinct cells, while the syncytiotrophoblast forms the outer multinucleated layer that invades the endometrium. The syncytiotrophoblast erodes endometrial tissue with enzymes, allowing the embryo to burrow into the stratum functionalis, and secretes hCG to maintain the corpus luteum and its continued progesterone production.
The endometrium undergoes the decidual reaction in response to implantation, with stromal cells enlarging and accumulating glycogen and lipids to become the decidua, which nourishes the early embryo. Implantation is complete by approximately day 14.
<image>A multi-panel figure showing fertilization and early development. Panel A: Fertilization in the ampulla of the uterine tube — a sperm approaching the secondary oocyte, with labeled corona radiata, zona pellucida, and oocyte plasma membrane. Insets show (i) the acrosomal reaction with release of hyaluronidase and acrosin, (ii) sperm binding to ZP3, (iii) the cortical reaction with cortical granule exocytosis and zona hardening. Panel B: A timeline of pre-embryonic development — the zygote at day 1, 2-cell stage, 4-cell stage, 8-cell stage, morula (day 3–4, solid ball in the uterine tube), and blastocyst (day 5, hollow sphere with trophoblast, inner cell mass, and blastocoel, now in the uterine cavity). Panel C: Implantation at days 6–10 — the blastocyst attaching to the endometrial surface with the syncytiotrophoblast invading the endometrium, cytotrophoblast underlying it, and the inner cell mass oriented toward the endometrium. The endometrial stroma shows the decidual reaction with enlarged stromal cells.</image>
III. Extraembryonic Membranes and the Placenta
Extraembryonic Membranes
Four extraembryonic membranes support embryonic development. The chorion is the outermost membrane, developing from the trophoblast plus underlying mesoderm. Its chorionic villi project into the endometrium and become the fetal portion of the placenta, containing fetal blood vessels. The amnion is the inner membrane surrounding the embryo and fetus, enclosing the amniotic cavity filled with amniotic fluid that cushions the fetus, maintains temperature, allows fetal movement, and prevents adhesions. The yolk sac forms blood cells during early development, is incorporated into the umbilical cord, and degenerates by week 8. The allantois forms the structural basis for the umbilical cord blood vessels and contributes to the urinary bladder.
The Placenta
The placenta becomes fully functional by week 12 (end of the first trimester). It is a disc-shaped organ weighing approximately 500 g at term with a diameter of about 20 cm. Its fetal portion consists of chorionic villi containing fetal capillaries. Its maternal portion is the decidua basalis (the endometrium deep to the implantation site) with blood-filled intervillous spaces (lacunae). The placental barrier consists of fetal capillary endothelium, connective tissue, cytotrophoblast, and syncytiotrophoblast (thinning as pregnancy progresses). This barrier separates maternal and fetal blood, which do not mix.
The placenta performs multiple vital functions. For gas exchange, oxygen diffuses from maternal blood to fetal blood while carbon dioxide diffuses in the opposite direction. Nutrient transfer involves glucose (by facilitated diffusion), amino acids (by active transport), fatty acids, vitamins, and minerals. Waste removal moves urea, uric acid, and bilirubin from fetal blood to maternal blood. For immune protection, maternal IgG antibodies cross the placenta to provide passive immunity for the newborn. As an endocrine organ, the placenta produces hCG, human placental lactogen (hPL), estrogen, progesterone, relaxin, and corticotropin-releasing hormone (CRH).
The umbilical cord connects the fetus to the placenta, containing 2 umbilical arteries (carrying deoxygenated blood from fetus to placenta) and 1 umbilical vein (carrying oxygenated blood from placenta to fetus), surrounded by Wharton's jelly (mucous connective tissue).
IV. Embryonic Development (Weeks 3-8)
This is the period of organogenesis during which all major organ systems are established. The embryo is extremely vulnerable to teratogens (alcohol, drugs, infections, radiation) during this time.
Gastrulation (Week 3)
During gastrulation, the inner cell mass reorganizes into the trilaminar embryonic disc with three germ layers. The ectoderm (outer layer) gives rise to skin epidermis, the nervous system (brain, spinal cord, peripheral nerves), sensory organs, and tooth enamel. The mesoderm (middle layer) gives rise to muscle, bone, cartilage, connective tissue, the cardiovascular system, kidneys, gonads, and blood. The endoderm (inner layer) gives rise to the epithelial lining of the GI tract, respiratory tract, urinary bladder, liver, pancreas, thyroid, and parathyroid.
Neurulation (Weeks 3-4)
During neurulation, the neural plate forms from ectoderm and folds to create the neural tube, which becomes the brain and spinal cord. Neural crest cells migrate from the neural folds to form the peripheral nervous system, melanocytes, adrenal medulla, and pharyngeal arch structures. Failure of neural tube closure produces neural tube defects (anencephaly, spina bifida), which are prevented by folic acid supplementation.
Key Events of Weeks 4-8
The heart begins beating around day 22-23. Limb buds appear at week 4, with digits forming by week 8. Facial features develop, and all major organ systems are at least rudimentarily present by week 8. By the end of week 8, the embryo measures approximately 3 cm in length and is referred to as a fetus from week 9 onward.
V. Fetal Development (Weeks 9-38)
Second Trimester (Weeks 13-26)
The second trimester is characterized by rapid growth in length, beginning of skeletal ossification, fetal movements felt by the mother (quickening, at approximately weeks 16-20), coverage of the body by lanugo (fine hair) and vernix caseosa (a waxy protective coating), and the beginning of surfactant production by the lungs in the late second trimester. The viability threshold is reached at approximately 24 weeks with intensive care support.
Third Trimester (Weeks 27-38)
The third trimester features rapid weight gain through fat deposition, maturation of the lungs with significantly increased surfactant production, the fetus typically assuming a head-down (vertex) position, accelerated brain development, transfer of maternal IgG for immune protection, and achievement of average birth weight (approximately 3.2-3.6 kg) and length (approximately 50 cm).
VI. Hormonal Changes During Pregnancy
Multiple hormones coordinate the maintenance and progression of pregnancy. hCG peaks at approximately 8-12 weeks, maintains the corpus luteum during the first trimester, and forms the basis of pregnancy tests. Progesterone is initially produced by the corpus luteum and then by the placenta (by week 8-12), maintaining the endometrium, suppressing uterine contractions, and preparing the breasts for lactation. Estrogen (primarily estriol) from the placenta stimulates uterine growth, breast development, and relaxation of pelvic ligaments. Human placental lactogen (hPL) from the placenta promotes breast development and has anti-insulin effects that raise maternal blood glucose, ensuring glucose availability for the fetus (and potentially causing gestational diabetes in susceptible women). Relaxin from the corpus luteum and placenta relaxes the pubic symphysis and dilates the cervix in preparation for delivery. Corticotropin-releasing hormone (CRH) from the placenta rises exponentially near term and may help initiate labor.
Maternal physiological adaptations during pregnancy include a 30-50% increase in blood volume (with dilutional anemia being common), a 30-40% increase in cardiac output, increased respiratory tidal volume (mediated by progesterone), a 50% increase in GFR, and morning sickness (nausea and vomiting) in the first trimester (likely related to hCG).
<image>A two-panel figure of placental structure and pregnancy hormones. Panel A: A cross-section of the mature placenta showing the fetal side (chorionic plate with branching chorionic villi containing fetal capillaries), the maternal side (decidua basalis with spiral arteries opening into intervillous spaces filled with maternal blood), the placental barrier separating maternal and fetal blood, the umbilical cord with two umbilical arteries and one umbilical vein, and arrows indicating the direction of gas and nutrient exchange. Panel B: A graph plotting the blood levels of key pregnancy hormones over 40 weeks of gestation — hCG peaking sharply at 8–12 weeks then declining, progesterone rising steadily (initially from corpus luteum, then from placenta, with the transition marked), estrogen rising gradually and accelerating in the third trimester, and hPL rising in parallel with placental growth. Key events are annotated on the timeline: implantation, placenta functional, quickening, viability, and term.</image>
VII. Parturition (Labor and Delivery)
Labor is initiated by a positive feedback mechanism involving multiple converging signals. Rising fetal cortisol stimulates placental CRH and estrogen production. The rising estrogen-to-progesterone ratio makes the uterine myometrium more excitable. Estrogen increases oxytocin receptors on myometrial cells and stimulates prostaglandin synthesis. The fetal head pressing on the cervix activates stretch receptors, triggering the Ferguson reflex and oxytocin release from the posterior pituitary in a positive feedback loop. Prostaglandins produced locally enhance myometrial contractions and soften the cervix.
Stages of Labor
Stage 1 (Dilation) is the longest stage, lasting approximately 6-12 hours for a first birth. Regular uterine contractions increase in frequency, duration, and intensity while the cervix dilates from 0 to 10 cm and effaces (thins). The amniotic membrane typically ruptures during this stage ("water breaks"). Stage 2 (Expulsion) lasts approximately 20 minutes to 2 hours, from full dilation to delivery of the infant. Strong contractions are aided by voluntary abdominal pushing, and the baby typically delivers head first (vertex presentation). Stage 3 (Placental) lasts approximately 5-30 minutes and involves delivery of the placenta ("afterbirth"). Continued uterine contractions separate the placenta from the uterine wall, and the placenta is examined to ensure complete delivery, as retained fragments can cause hemorrhage and infection.
VIII. Lactation
Mammary Gland Anatomy
Each breast contains 15-20 lobes of glandular tissue arranged radially around the nipple. Each lobe consists of lobules containing alveoli (the milk-secreting cells), which drain into lactiferous ducts that converge to form lactiferous sinuses opening at the nipple. The breast is supported by suspensory (Cooper's) ligaments and adipose tissue.
Hormonal Control of Lactation
During pregnancy, estrogen, progesterone, hPL, and prolactin stimulate mammary gland development, including duct growth and alveolar differentiation. However, the high levels of progesterone and estrogen actively inhibit milk secretion during pregnancy despite elevated prolactin levels. After delivery, the sudden drop in estrogen and progesterone (due to loss of the placenta) removes this inhibition, allowing prolactin to stimulate milk production.
Prolactin from the anterior pituitary stimulates milk synthesis and secretion by alveolar cells. Its levels are maintained by the suckling reflex: infant suckling generates sensory nerve impulses that signal the hypothalamus to decrease dopamine (prolactin-inhibiting hormone), resulting in increased prolactin release. Oxytocin from the posterior pituitary stimulates the milk ejection (let-down) reflex by causing contraction of myoepithelial cells surrounding alveoli, propelling milk into the lactiferous ducts and sinuses. Oxytocin release is also stimulated by the suckling reflex and can be triggered by hearing the baby cry (a conditioned response). Additionally, oxytocin promotes uterine contractions postpartum, aiding uterine involution and reducing bleeding.
Colostrum and Mature Milk
Colostrum is produced in the first 2-3 days postpartum. It is rich in IgA antibodies, proteins, vitamin A, and minerals but lower in fat and lactose than mature milk. It provides passive immunity and promotes colonization of beneficial gut bacteria. Mature milk, produced by day 4-5, is rich in lactose, fat, casein, vitamins, and minerals, and contains IgA, lysozyme, and lactoferrin.
<image>A multi-panel figure on lactation. Panel A: A sagittal cross-section of a lactating breast showing the arrangement of lobes with lobules and alveoli, lactiferous ducts converging toward the nipple, lactiferous sinuses beneath the areola, adipose tissue, and suspensory ligaments. An inset magnifies a single alveolus showing secretory epithelial cells surrounding the lumen, myoepithelial cells wrapping around the alveolus, and a small duct draining the lumen. Panel B: The neuroendocrine reflex arc of lactation — an infant suckling at the breast sends sensory nerve impulses via spinal afferents to the hypothalamus. Two pathways diverge: (1) the hypothalamus signals the anterior pituitary to release prolactin (via decreased dopamine), which acts on alveolar cells to produce milk, and (2) the hypothalamus signals the posterior pituitary to release oxytocin, which acts on myoepithelial cells to contract and eject milk. Negative feedback from prolactin on GnRH is shown, explaining lactational amenorrhea.</image>
IX. Clinical Correlations
Ectopic pregnancy involves implantation outside the uterus, usually in the uterine tube, with risk of rupture and hemorrhage. Placenta previa occurs when the placenta implants over the cervical os, causing painless bleeding and potentially requiring cesarean delivery. Preeclampsia presents as hypertension plus proteinuria after 20 weeks and can progress to eclampsia (seizures), threatening both mother and fetus. Gestational diabetes results from glucose intolerance during pregnancy mediated by hPL-induced insulin resistance, with risk of macrosomia (a large baby). Rh incompatibility (hemolytic disease of the newborn) occurs when an Rh-negative mother carries an Rh-positive fetus and is prevented with RhoGAM. Neural tube defects are prevented by adequate folic acid intake before and during early pregnancy. Fetal alcohol spectrum disorders are caused by maternal alcohol consumption and represent the leading preventable cause of intellectual disability.
