Events of Gestation

Human development begins with fertilization when a sperm penetrates an egg. The fertilized egg proceeds through several progressive stages. Gestation, or pregnancy, is the carrying and development of an embryo, which forms into a fetus in the uterus, from fertilization and implantation until childbirth. Conception includes fertilization and implantation. A fertilized ovum must be implanted in the uterine wall for gestation to take place. In about half of all situations, fertilized eggs are expelled from the female's body without undergoing implantation. A full pregnancy period takes 280 days, or 40 weeks, and is measured from the start of the female's last menstrual period. Human gestation involves three stages: the germinal, or preembryonic, stage, the embryonic stage, and the fetal stage. The gestational age of a pregnancy is marked from the start of the female's last menstrual period. If the last menstrual period began on April 1 and the current date is May 13, then the gestational age of the pregnancy is six weeks.

Successful fertilization of an egg usually takes place in the widened portion of the fallopian tube nearest to the ovary, as eggs must be fertilized within 12 to 24 hours of ovulation. Very few sperm reach that point, as they are deterred by vaginal acid, cervical mucus, uterine leukocytes, or simply gravity. The first sperm to reach an egg does not fertilize it. Instead, it and many others after it penetrate the egg's surrounding granulosa cells of the corona radiata and then the underlying zona pellucida. This process is called an acrosomal reaction because each sperm releases enzymes from the acrosome on its head. The acrosomal reaction is the release of enzymes from the head of the sperm, which causes the sperm to penetrate the zona pellucida of the ovum, allowing fertilization to take place. Many sperm cells may begin the acrosomal reaction, but only the sperm cell that successfully fertilizes the egg completes it. Fertilization is normally followed by the cortical reaction when the cortical granules fuse with the cell membrane of the egg and release enzymes that cause changes in the zona pellucida to make it impenetrable to sperm. Fertilization produces a zygote, which develops into a preembryo, then an embryo, and eventually a fetus. A zygote is the fertilized egg, the single-celled union of the male gamete, or sperm, with the female gamete, or egg. A gamete is a mature haploid cell carrying the genetic material for potential offspring.

During the two-week preembryonic stage, an embryo gradually develops from the zygote. A zygote is a fertilized egg—the single-celled union of the male gamete or germ cell, the sperm, with the female gamete or germ cell, the egg. The preembryonic stage begins with cleavage, rapid mitotic divisions of the zygote during the three days postfertilization. A blastomere forms, which is one of the two daughter cells produced by the first cleavage of the zygote following fertilization. Blastomeres divide repeatedly, doubling in number with each division.

The dividing preembryo moves down the fallopian tube. As it reaches the uterus approximately 72 hours postovulation, the preembryo is considered a morula. A morula is a spherical bundle of 16 or more cells, or blastomeres, in the preembryonic stage produced by successive divisions. The morula, now a blastocyst, remains free in the uterus for four to five days, dividing into approximately 100 cells. The zona pellucida then disintegrates, which releases the dividing preembryo, or blastocyst. A blastocyst is the pre-embryonic stage consisting of an inner cell mass called the embryoblast. This structure is surrounded by the trophoblast, which is the outer squamous cell layer of the blastocyst. Eventually the trophoblast develops into part of the placenta, and the embryoblast develops into the embryo.

The blastocyst attaches to the endometrium, the uterus lining, around six days after ovulation. This initiates implantation—the portion of the preembryonic stage when the blastocyst burrows or implants into the uterine wall. Implantation occurs as the trophoblast releases enzymes that stimulate the endometrium to thicken. The trophoblast separates into two layers, the inner cytotrophoblast and the syncytiotrophoblast, that will form the embryo's portion of the placenta, which is a temporary vascular organ that allows the diffusion of essential materials from the mother to the embryo. The deeper cytotrophoblast continues to divide, and the more superficial syncytiotrophoblast is a nondividing mass with multiple nuclei. The syncytiotrophoblast extends into the uterus, and the endometrium responds by growing over and enclosing the trophoblast. A hormone secreted by the trophoblast, human chorionic gonadotropin (HCG), stimulates the corpus luteum, a hormone-generating structure in the ovary, to produce estrogen and progesterone. Progesterone suppresses menstruation, is essential for the implantation of the fertilized ovum, and maintains pregnancy. The mother's HCG levels climb until the end of the second month, when the chorion has developed. The chorion is an extraembryonic membrane that takes over the corpus luteum's hormone production, rendering HCG unnecessary. At this point, the ovaries become inactive because there is no need to release additional eggs.

As implantation ends, the embryoblast goes through embryogenesis, with blastomeres arranging into the three primary germ layers: (from inside to out) the endoderm, mesoderm, and ectoderm. This happens through gastrulation, which is the process in which the embryo changes. The layers develop through a series of steps. Ectoderm and endoderm flatten into the embryonic disc, and cells migrate along and within a lateral groove called the primitive streak to form mesoderm. Upon completion of embryogenesis, the developing individual is a two-week-old, 2-millimeter-long embryo. An embryo is the developing human formed from the end of week two through week eight of gestation. Embryonic stages begin after germ layers form and end, as all organ systems appear. Germ layers form during gastrulation in the early embryonic stage beginning week three of the gestational stage. In addition to organ development, embryonic stages mark the start of nutrient delivery through the placenta and membranes forming outside the embryo.

The placenta is a temporary vascular organ that normally forms on the uterine wall and through which nutrients and oxygen diffuse from the maternal bloodstream to the developing embryo or fetus. Prior to placental development, the trophoblast makes up protective outer layers around the blastocyst and nourishes the blastocyst by digesting nutrient-rich endometrial cells into nutritious fluid. Placental nutrition gradually phases out trophoblastic nutrition, which ends at 12 weeks. The trophoblast is replaced by the chorion as the outermost extra-embryonic membrane. The chorion forms the fetal contribution to the placenta and secretes hormones, removes wastes, and provides fetal nutrition. During placenta formation, chorionic villi extend from the chorionic wall, which becomes the chorionic plate of the placenta. Chorionic villi are branching protrusions of the embryo's syncytiotrophoblast that penetrate progressively deeper into the endometrium, providing extensive contact with maternal blood. There is no direct mixing of maternal blood with the blood of the embryo and later the fetus. However, water, oxygen, lipids, and nutrients pass from mother to fetus, while waste products pass from fetus to mother for removal. All exchanges of nutrients and gases occur across capillary walls.

The umbilical cord is a tissue cord connecting the embryo or fetus to the placenta through three blood vessels, which are the uterine artery and vein, the umbilical vein, and the umbilical artery. These vessels deliver oxygen and nutrients and remove wastes. Both the uterus and the umbilical cord are supplied with oxygen through their respective arteries.

As the embryo develops, it requires four extra-embryonic membranes, which provide protection and nutrition for the embryo. First, the amnion forms a transparent sac that fully encloses the embryo. Formed from the embryonic disc, the amnion fills with amniotic fluid. Amniotic fluid is a clear fluid that surrounds and cushions the embryo within the amnion and enables movement and development. The yolk sac is an extra-embryonic membrane forming a small sac that contributes to digestive tract development and formation of blood, sperm, and egg cells. It arises from the embryonic disc. The allantois is an extra-embryonic membrane consisting of endoderm that grows out from the yolk sac. It incorporates into the umbilical cord and urinary bladder. Organs develop within the embryo. They arise from particular germ layers related to body location (exterior to interior). The innermost germ layer of the embryo, the endoderm, develops into structures of the respiratory, digestive, and endocrine systems. The medial germ layer of the embryo, the mesoderm, develops into the skeleton, blood vessels, and other organs. The outermost germ layer of the embryo, the ectoderm, develops into the skin and other external structures.

The fetus occurs in the final stage of gestational development. The fetal stage extends from week 9 to week 40 of gestation (birth) and involves major growth and differentiation of organ systems.

• 8 weeks: The embryo is typically 3 centimeters (cm) long and weighs 1 gram (g). It has closed eyes, undifferentiated genitals (not distinguished by sex), and a heart that circulates blood.
• 12 weeks: The fetus has well-developed eyes and limbs and a liver producing bile. The fetus is able to swallow and to generate urine. Male and female genitals are recognizable. Ossification (bone formation) has begun.
• 16 weeks: The fetus exhibits a distinct face, kidneys, hair, and a detectable heartbeat. It is 14 cm long and weighs 100 g. Measurement is based on the crown-to-rump length (from the top of the head to the bottom of the buttocks).
• 20 weeks: The body of the fetus is covered in hair called lanugo, and its skin is coated by vernix, which is a substance composed of sebum, skin cells, and lanugo. The fetus's movements can be felt by the mother.
• 24 weeks: The fetus has eyelashes and open eyes, and the lungs start producing surfactant, an important lipoprotein complex. The fetus's skin is wrinkled. It has begun gaining weight rapidly, and its size varies. Typically, a fetus at this stage measures from 27 to 35 cm long and weighs 550 to 800 g.
• 28 weeks: The fetus has usually turned upside (head) down. In males, the testes have descended into the scrotum. At this stage of development, some fetuses undergo premature birth. Fetuses born after 25 weeks generally survive.
• 32 weeks: The fetus primarily gains weight. It begins storing fat, so its skin is less wrinkled, and is typically 41 to 45 cm long and weighs 2,000 to 2,300 g. At the end of gestation, the fetus averages 50 cm in length and weighs 3,200 to 3,400 g. It has gained more fat and shed the lanugo.

Development of all organ systems is complicated and gradual. For instance, development of external genitalia begins at five weeks of gestation and ends near birth. At first, males and females are the same, exhibiting a genital tubercle, genital folds, urethral grooves, and labioscrotal swellings. At 10 weeks, genital structures remain similar but are larger in males. From the genital tubercle, testosterone has triggered development of a glans penis in males. Without testosterone, females develop a glans clitoris. Both sexes have open urethral grooves. By birth, external genitalia have developed fully. Labioscrotal swellings form into the labia majora in females and the scrotum in males. Genital folds form labia majora in females but fuse into the body of the penis in males. The urethral groove remains open in females but is closed in males.