Pregnancy and Human Development

From Egg to Embryo

Pregnancy - events from fertizilation until birth.

Conceptus - the developing offspring.

Gestation period - from the last menstrual period until birth.

Preembryonic development lasts from fertilization through the first 2 weeks of development; the conceptus is known as a preembryo.

The 3rd through 8th weeks after fertilization is the embryonic period, the conceptus is known as the embryo.

The fetal period extends from the 9th week after fertilization through birth, the conceptus is known as a fetus.

Accomplishing Fertilization

Fertilization occurs when a sperm fuses with an egg to form a zygote. This usually occurs when the ovum is approximately 1/3 of the way down the uterine tube.

Millions of sperm ejaculated into the female reproductive tract are lost due to leakage from the vaginal canal, destruction by the acidic environment of the vagina, inability to pass the cervical mucus, or destruction by defense cells of the uterus.

In order to fertilize an egg, sperm must be capacitated, a process involving weakening of the sperm cell membrane in order to allow release of acrosomal hydrolytic enzymes.  During their journey through the cervical mucus, the uterus, and the uterine tubes cholesterol is depleted from their membranes, making them more fragile. This process takes somewhere around 6 - 8 hours.

When sperm cells bind to the zona pellucida surrounding the egg, they undergo an acrosomal reaction, where acrosomal enzymes are released to the oocyte. 

Hundreds of sperm cells must release their acrosomal enzymes before fertilization can occur.  When the intracellular binding between granulosa cells is disrupted and holes are digested in the zona pellucida membrane receptors on the oocyte membrane are exposed.

Once a sperm cell binds to membrane receptors on the oocyte membrane, its nucleus is pulled into the cytoplasm of the oocyte. 

Polyspermy, or fertilization by more than one sperm cell, leads to a lethal number of chromosomes, and must be prevented. 

The fast block to polyspermy occurs when the membrane of the oocyte depolarizes and prevents similar binding by other sperm cells. 

The slow block to polyspermy results in destruction of sperm receptors, and the formation of a swollen membrane that removes other sperm cells from the surface of the oocyte. 

After a sperm enters an oocyte, it loses its tail and midpiece, and migrates to the center of the oocyte while the oocyte completes meiosis II. 

After meiosis II is completed, male and female pronuclei fuse and produce a zygote, which almost immediately enters into mitosis.

Preembryonic Development

Preembryonic development begins with fertilization and continues with the movement of the preembryo to the uterus, where it implants in the uterine wall. 

The mitotic divisions after fertilization occur without much growth between divisions, resulting in progressively smaller cells, a process called cleavage. 

Cleavage forms two identical cells, blastomeres, which then form a morula, a hollow ball of 16 or more cells, by 72 hours.  The cells continue to divide and begin to compact, developing a fluid filled blastocyst cavity.

After 4–5 days, the blastocyst escapes from the degrading zona pellucida to implant in the uterine wall.  The blastocyst consists of a single later of large, flattened cells called trophoblast cells and a small cluster of rounded cells, called the inner cell mass.

Implantation occurs after 6–7 days; the trophoblast cells express integrin and selectin proteins on thier surface which bind to extracellular matrix components of the endometrial cells and selectin-binding carbohydrates on the inner uterine wall. The trophoblast cells that lie over the inner cell mass adhere to the endometrium and produce growth factors and digestive enzymes that irritate the endometrium. 

Uterine capillaries become permeable and leaky, and the trophoblast proliferates, forming two layers, the inner cytotrophoblast and the outer syncytiotrophoblast. 

The cytotrophoblast maintains cell boundaries and develops into the chorion after implantation.

The syncytiotrophoblast results from cell fusion (forms a multi-nucleated cytoplasmic mass) and invades the endometrium, digesting the endometrial cells and allowing the blastocyst to burrow into the endometrium.

The blastocyst is surrounded by blood from the leaky uterine capillaries and walled off from the uterine cavity by proliferating endometrial cells.

Trophoblast cells secrete human chorionic gonadotropin (hCG), which acts on the corpus luteum to keep it secreting estrogen and progesterone.  The chorion continues to secrete hCG until the placenta is able to take over estrogen and progesterone production.

Placentation is the formation of the placenta, and is the process of proliferation of the trophoblast. The inner cell mass of the trophoblast produces a layer of extraembryonic mesoderm that lines the inner surface of the trophoblast and together they become the chorion.

The chorion develops chorionic villi, which are in contact with maternal blood. The mesoderm in the core of the villi form new blood vessels, which extend into the embryo as umbilical arteries and veins. Continued erosion of the endometrial cells open up intervillus spaces or lacuna in the stratum fuctionalis, wihch are filled with maternal blood.

The endometrial cells between the chorionic villi and the stratum basalis form the the decidua basalis; the endometrial cells that form the uterine lining over the implanted embryo forms the decidua capsularis.

 

The placenta is fully functional as a nutritive, respiratory, excretory, and endocrine organ by the end of the third month of gestation.

Events of Embryonic Development

Formation and Roles of the Embryonic Membranes

While implantation is occurring, the blastocyst is being converted into a gastrula, in which three primary germ layers form and embryonic membranes develop. The first step is when the inner cell mass differentiates into two layers, the ipiblast and hypoblast. Thes cells form two of the four embryonic membranes.

The amnion develops from the epiblast and forms the fluid-filled transparent sac ultimately containing the embryo. The amnion provides a buoyant environment that protects the embryo from physical trauma and maintains a constant temperature. The amniotic fluid allows developing body parts to move freely, advoids adhesion, and assists musculoskeletal development. It is initially derived from the maternal blood but after fetal renal development fetal urine contributes to the make-up of the amniotic fluid. 

The yolk sac forms from the cells of the hypoblast. Rather than provide nutrition for the embryo (as in many animals) the yolk sac forms part of the gut, produces the earliest blood cells and blood vessels, and is the source of germ cells that migrate into the embryo to seed the gonads.  Nutrition is provided by the placenta.

The allantois is an outpocketing of the yolk sac that is a disposal site for solid wastes in animals that develop in shells; in humans it is the structural base for the umbilical cord that links the embryo to the placenta, and becomes part of the urinary bladder. 

The umbilical cord contains the umbilical arteries and vein, a core of embryonic connective tissue (Wharton's jelly) and is covered externally by the amniotic membrane.

The chorion helps to form the placenta, and encloses the embryonic body and all other membranes.

 

Gastrulation: Germ Layer Formation

Gastrulation is the process, occuring in the third week, of transforming the two-layered embryonic disc to a three-layered embryo containing three germ layers: ectoderm, mesoderm, and endoderm. 

Gastrulation begins with the appearance of the primitive streak, which establishes the long axis of the embryo. 

The endoderm gives rise to epithelial linings of the gut, respiratory, and urogenital systems, and associated glands. 

The mesoderm gives rise to all types of tissues not formed by ectoderm or endoderm, such as muscle tissue.

The ectoderm gives rise to structures of the nervous system and the epidermis.

Organogenesis: Differentiation of the Germ Layers

Organogenesis is the formation of organs and organ systems; by the end of the embryonic period, all organ systems are recognizable. 

Neurulation is the process of differentiation of ectoderm that gives rise to the formation of the brain and spinal cord, and is the first event of organogenesis. 

As the embryo develops from a flat plate of cells, it rolls into a tube and the inferior endoderm becomes the lining of the primitive gut. 

Neurulation

Specialization of the endoderm involves lateral folding into a tube, which encloses part of the yolk sac as the eges fuse. The tube of endoderm is the primitive gut and forms the epithelial lining of the GI tract, the organs of the GI tract, and oral and anal openings when the tube perforates at either end.

Respiratory mucosa forms from the foregut (pharyngeal endoderm) ; the thyroid, parathyroids, and thymus form from the pharyngeal endoderm, the liver and pancreas from the midgut (intestinal mucosa).

Endodermal Differentiation

Mesodermal specialization forms the notochord, and gives rise to the dermis, parietal serosa, bones, muscles, cardiovascular structures, and connective tissues. 

Mesodermal Differentiation

By 3 1/2 weeks, the embryo has a blood vessel system and a pumping heart.

Vascular modifications include umbilical arteries and veins, a ductus venosus, and the foramen ovale and ductus arteriosus.

 

Events of Fetal Development

The fetal period extends from weeks 9–38, and is a time of rapid growth of body structures established in the embryo. 

During the first half of the fetal period, cells are still differentiating into specific cell types to form the body’s distinctive tissues.

Effects of Pregnancy on the Mother

Anatomical Changes

The female reproductive organs and breasts become increasingly vascular and engorged with blood. 

The uterus enlarges dramatically, causing a shift in the woman’s center of gravity and an accentuated lumbar curvature (lordosis). 

Placental production of the hormone relaxin causes pelvic ligaments and the pubic symphysis to soften and relax. 

There is a normal weight gain of around 28 pounds, due to growth of the fetus, maternal reproductive organs, and breasts, and increased blood volume. 

Metabolic Changes

As the placenta enlarges, it produces human placental lactogen, which woks with estrogen and progesterone to promote maturation of the breasts for lactation. 

Human placental lactogen also promotes the growth of the fetus, and exerts a glucose-sparing effect on maternal metabolism. 

Human chorionic thyrotropin from the placenta increases maternal metabolic rate. 

Physiological Changes

Many women suffer morning sickness during the first few months of pregnancy, until their systems adapt to elevated levels of estrogen and progesterone. 

Heartburn often results from the displacement of the esophagus, and constipation may result due to the decreased motility of the digestive tract.  

The kidneys produce more urine, since there is additional fetal metabolic waste. 

Vital capacity and respiratory rate increases, but there is a decrease in residual volume, and many women suffer from difficult breathing, or dyspnea. 

Blood volume increases to accommodate the needs of the fetus, so blood pressure and heart rate rise, increasing cardiac output.

Parturition (Birth)

Parturition is the process of giving birth, and usually occurs within 15 days of the calculated due date, which is 280 days from the last menstrual period. 

Initiation of Labor

Estrogen levels peak, stimulating myometrial cells of the uterus to form abundant oxytocin receptors, and antagonizing the quieting effect of progesterone on uterine muscle. 

Fetal cells produce oxytocin, which promotes the release of prostaglandins from the placenta, and further stimulates uterine contraction. 

Increasing emotional and physical stresses activate the mother’s hypothalamus, which signals the release of oxytocin.

Expulsive contractions are aided by a change that occurs in an adhesive protein, fetal fibronectin, converting it to a lubricant.

Stages of Labor

The dilation stage of labor extends from onset of labor to the time when the cervix is fully dilated by the baby’s head, at about 10 cm in diameter. 

The expulsion stage extends from full dilation until the time the infant is delivered. 

When the baby is in the vertex, or head first, position, the skull acts as a wedge to dilate the cervix.

Crowning occurs when the baby’s head distends the vulva, and once the head has been delivered, the rest of the baby follows much more easily. 

After birth, the umbilical cord is clamped and cut.

During the placental stage, uterine contractions cause detachment of the placenta from the uterine wall, followed by delivery of the placenta and membranes (afterbirth).

Adjustments of the Infant to Extrauterine Life

The Apgar score is an assessment of the infant’s physiological status based on heart rate, respiration, color, muscle tone, and reflexes.

Taking the First Breath

Once the placenta is no longer removing carbon dioxide from the blood, it builds up in the infant’s blood, resulting in acidosis that signals the respiratory control centers.

The transitional period is the 6–8 hours after birth characterized by intermittent waking periods in which the infant’s heart rate, respiratory behavior, and body temperature fluctuate.

Occlusion of Special Fetal Blood Vessels and Vascular Shunts

After birth, the umbilical arteries and veins constrict and become fibrosed, becoming the medial umbilical ligaments, superior vesical arteries of the bladder, and the round ligament of the liver, or ligamentum teres.

The ductus venosus closes, and is eventually converted to the ligamentum venosum.

A flap of tissue covers the foramen ovale, ultimately sealing it and becoming the fossa ovalis, while the ductus arteriosus constricts, becoming the ligamentum arteriosus.

Lactation

Lactation is the production of milk by the hormone-prepared mammary glands.

Rising levels of placental estrogens, progesterone, and lactogen stimulate the hypothalamus to produce prolactin-releasing hormone (PRH), which promotes secretion of prolactin by the anterior pituitary. 

Colostrum, a high-protein, low-fat product is initially secreted by the mammary glands, but after two to three days, true milk is produced. 

Nipple stimulation during nursing sends neural signals to the hypothalamus, resulting in production of PRH and a burst of prolactin that stimulates milk production for the next feeding. 

Oxytocin causes the let-down reflex, resulting in the release of milk from the alveoli of the mammary glands in both breasts. 

Advantages of breast milk are: better absorption and more efficient metabolism of many components; antibodies and other chemicals that protect the infant; a natural laxative effect that helps to prevent physiological jaundice; and encouragement of the natural intestinal fauna.

Assisted Reproductive Technology and Reproductive Cloning

Hormones can be used to increase sperm or egg production and surgery can be used to open blocked tubes.

Assisted reproductive technology involves surgically removing oocytes from a woman’s ovaries, fertilizing the eggs and returning them to the woman’s body.

Cloning involves the placing of a somatic cell nucleus into an oocyte.