Sexual Reproduction in Humans

The Problems to be Solved

• differ in structure ("anisogamy") and
• are contributed by different parents.

• motility to be able to meet and unite
• food to nourish the developing embryo.

• sperm that are motile (and small)
• eggs that contain food.

Sex Organs of the Human Male

• production of sperm
• delivery of these to the reproductive tract of the female.

Each testis is packed with seminiferous tubules (laid end to end, they would extend more than 20 meters) where spermatogenesis occurs.

Spermatogenesis

The walls of the seminiferous tubules consist of diploid spermatogonia, stem cells that are the precursors of sperm.

• divide by mitosis to produce more spermatogonia or
• differentiate into spermatocytes.

Meiosis of each spermatocyte produces 4 haploid spermatids. These then differentiate into sperm, losing most of their cytoplasm in the process.

Sperm

• a head, which has
  • an acrosome at its tip and
  • contains a haploid set of chromosomes in a compact, inactive, state.
• a midpiece containing mitochondria and a centriole
• a tail

This electron micrograph (courtesy of Dr. Don W. Fawcett and Susumu Ito) shows the sperm cell of a bat. Note the orderly arrangement of the mitochondria. They supply the ATP to power the whiplike motion of the tail.

An adult male manufactures over 100 million sperm cells each day. These gradually move into the epididymis and the first portion of the vas deferens, where they undergo further maturation and are stored.

LH

FSH

Sex Organs of the Human Female

The responsibility of the female mammal for successful reproduction is considerably greater than that of the male.

• manufacture eggs
• be equipped to receive sperm from the male
• provide an environment conducive to fertilization
• nourish the developing baby not only before birth but after.

Oogenesis

• develop into primary oocytes
• begin the first steps of meiosis and then
• stop.

The primary oocyte grows much larger and completes the first meiotic division, forming a large secondary oocyte and a small polar body that receives little more than one set of chromosomes. Which chromosomes end up in the egg and which in the polar body is entirely a matter of chance. In humans, the first polar body does not complete meiosis.

As in the diagram for spermatogenesis, the behavior of the chromosomes is greatly simplified.

The photomicrograph (courtesy of Turtox) shows polar body formation during oogenesis in the whitefish. Even allowing for the fact that fish eggs are larger than mammalian eggs, you can readily see how the polar body gets little more than one set of chromosomes.

• a broadening of the pelvis
• development of the breasts
• growth of hair around the genitals and in the armpits
• development of adipose tissue leading to the more rounded body contours of adult women.

Ovulation

Ovulation occurs about two weeks after the onset of menstruation. In response to a sudden surge of LH, the follicle ruptures and discharges a secondary oocyte. This is swept into the open end of the fallopian tube and begins to move slowly down it.

Copulation and Fertilization

The mixture of sperm and accessory fluids is called semen. It passes through the urethra and is expelled into the vagina.

Physiological changes occur in the female as well as the male in response to sexual excitement, although these are not as readily apparent. In contrast to the male, however, such responses are not a prerequisite for copulation and fertilization to occur.

Once deposited within the vagina, the sperm proceed on their journey into and through the uterus and on up into the fallopian tubes. It is here that fertilization may occur if an "egg" is present (strictly speaking, it is still a secondary oocyte until after completion of meiosis II).

The same path allows other enzymes to leave the cytoplasm of the egg. Within moments, these act on the zona making it impermeable to the other sperm that arrive.

The male and female pronuclei move toward each other. Their nuclear envelopes disintegrate. A spindle is formed, and a full diploid set of chromosomes assembles on it. The fertilized egg or zygote is now ready for its first mitosis.

Pregnancy

Embryonic development begins while the fertilized egg is still within the fallopian tube. The developing embryo travels down the tube, reaching the uterus in three or four days. As a result of repeated mitotic divisions and some migration of cells, a hollow ball of cells is formed called the blastocyst. Approximately one week after fertilization, the blastocyst embeds itself in the thickened wall of the uterus, a process called implantation, and pregnancy is established.

• Three or four blastocyst cells develop into the inner cell mass, which will become the fetus and, ultimately, the baby.
• The remaining 100 or so cells form the trophoblast, which will produce the four extraembryonic membranes. These will play vital roles during development but will be discarded at the time of birth.

• receiving food
• receiving oxygen and discharging carbon dioxide
• discharging urea and other wastes
• receiving antibodies (chiefly of the IgG class). These remain for weeks after birth, protecting the baby from the diseases to which the mother is immune.

The umbilical cord connects the fetus to the placenta. It receives deoxygenated blood from the iliac arteries of the fetus and returns oxygenated blood to the liver and on to the inferior vena cava.

Because its lungs are not functioning, circulation in the fetus differs dramatically from that of the baby after birth. While within the uterus, blood pumped by the right ventricle bypasses the lungs by flowing through the foramen ovale and the ductus arteriosus.

Although the blood in the placenta is in close contact with the mother's blood in the uterus, intermingling of their blood does not normally occur. However, some of the blood cells of the fetus usually do get into the mother's circulation - where they have been know to survive for decades. This raises the possibility of doing prenatal diagnosis of genetic disorders by sampling the mother's blood rather than having to rely on the more invasive procedures of amniocentesis and chorionic villus sampling (CVS).

Far rarer is the leakage of mother's blood cells into the fetus. However, it does occur. A few pregnant women with leukemia or lymphoma have transferred the malignancy to their fetus. Some babies have also acquired melanoma from the transplacental passage of these highly-malignant cells from their mother.

During the first 2 months of pregnancy, the basic structure of the baby is being formed. This involves cell division, cell migration, and the differentiation of cells into the many types found in the baby. During this period, the developing baby - called an embryo - is very sensitive to anything that interferes with the steps involved. Virus infection of the mother, e.g., by rubella ("German measles") virus or exposure to certain chemicals may cause malformations in the developing embryo. Such agents are called teratogens ("monster-forming"). The tranquilizer, thalidomide, taken by many pregnant European women between 1954 and 1962, turned out to be a potent teratogen and was responsible for the birth of several thousand deformed babies.

By 3 months, all the systems of the baby have been formed, at least in a rudimentary way. From then on, development of the fetus, as it is now called, is primarily a matter of growth and minor structural modifications. The fetus is less susceptible to teratogens than is the embryo.

The placenta is an allograft

One of the greatest unsolved mysteries in immunology is how the placenta survives for 9 months without being rejected by the mother's immune system. Every cell of the placenta carries the father's genome (a haploid set of his chromosomes); including one of his #6 chromosomes where the genes for the major histocompatibility antigens are located.

Thus the placenta is immunologically as foreign to the mother as a kidney transplant would be.

Yet it thrives.

Despite a half-century of research, the mechanism for this immunologically privileged status remains uncertain. But one thing is clear:

The mother is not intrinsically tolerant of the father's antigens.

Some evidence:

• She will promptly reject a skin transplant from the father.
• She develops antibodies against his histocompatibility antigens expressed by the fetus. In fact, women who have borne several children by the same father are often excellent sources of anti-HLA serum for use in tissue typing.

• The placenta does not express class II histocompatibility antigens.

  Discussion of the role of class II antigens in immunity.

• The class I histocompatibility antigens that it does express are only weakly immunogenic.
• A recent report shows that in normal mice, the cells of the placenta degrade the amino acid tryptophan. Tryptophan is essential for T-cell function. When mice were treated with an inhibitor of the Trp-degrading enzyme, their fetuses were promptly aborted by the action of the mother's lymphocytes. (D. H. Munn, et. al., Science, 281: 1191, 21 Aug 1998.)

Birth and Lactation

The infant's lungs expand, and it begins breathing. This requires a major switchover in the circulatory system. Blood flow through the umbilical cord, ductus arteriosus, and foramen ovale ceases, and the adult pattern of blood flow through the heart, aorta, and pulmonary arteries begins. In some infants, the switchover is incomplete, and blood flow through the pulmonary arteries is inadequate. Failure to synthesize enough nitric oxide (NO) is one cause.

Shortly after the baby, the placenta and the remains of the umbilical cord (the "afterbirth") are expelled.

At the time of birth, and for a few days after, the mother's breasts contain a fluid called colostrum. It is rich in calories and protein, including antibodies that provide passive immunity for the newborn infant.

• Its synthesis is stimulated by the pituitary hormone prolactin.
• Its release is stimulated by a rise in the level of oxytocin when the baby begins nursing.