Human Gametogenesis and Fertilization
المؤلف:
Cohn, R. D., Scherer, S. W., & Hamosh, A.
المصدر:
Thompson & Thompson Genetics and Genomics in Medicine
الجزء والصفحة:
9th E, P20-22
2025-11-05
139
The cells in the germline that undergo meiosis, primary spermatocytes or primary oocytes, are derived from the zygote by a long series of mitoses before the onset of meiosis. Male and female gametes have different histories, marked by different patterns of gene expression that reflect their developmental origin as an XY or XX embryo. The human primordial germ cells are recognizable by the fourth week of development outside the embryo proper, in the endoderm of the yolk sac. From there, they migrate during the sixth week to the genital ridges and associate with somatic cells to form the primitive gonads, which soon differentiate into testes or ovaries, depending on the cells’ sex chromosome constitution (XY or XX), as we examine in greater detail in Chapter 6. Both spermatogenesis and oogenesis require meiosis but have important differences in detail and timing that may have clinical and genetic consequences for the offspring. Female meiosis is initiated once, early during fetal life, in a limited number of cells. In contrast, male meiosis is initiated continuously in many cells from a dividing cell population throughout the adult life of a male.
In the female, successive stages of meiosis take place over several decades—in the fetal ovary before the female in question is even born, in the oocyte near the time of ovulation in the sexually mature female, and after fertilization of the egg that can become that female’s off spring. Although postfertilization stages can be studied in vitro, access to the earlier stages is limited. Testicular material for the study of male meiosis is less difficult to obtain, inasmuch as testicular biopsy is included in the assessment of many men attending infertility clinics. Much remains to be learned about the cytogenetic, bio chemical, and molecular mechanisms involved in nor mal meiosis and about the causes and consequences of meiotic irregularities.
Spermatogenesis
The stages of spermatogenesis are shown in Fig. 1. The seminiferous tubules of the testes are lined with spermatogonia, which develop from the primordial germ cells by a long series of mitoses and are in different stages of differentiation. Sperm (spermatozoa) are formed only after sexual maturity is reached. The last cell type in the developmental sequence is the primary spermatocyte, a diploid germ cell that undergoes meiosis I to form two haploid secondary spermatocytes. Secondary spermatocytes rapidly enter meiosis II, each forming two spermatids, which differentiate without further division into sperm. In humans, the entire process takes approximately 64 days. The enormous number of sperm produced, typically approximately 200 million per ejaculate and an estimated 1012 in a lifetime, requires several hundred successive mitoses.
Fig1. Human spermatogenesis in relation to the two meiotic divisions. The sequence of events begins at puberty and takes approximately 64 days to be completed. The chromosome number (46 or j23) and the sex chromosome constitution (X or Y) of each cell are shown. (Modified from Moore KL, Persaud TVN: The developing human: clinically oriented embryology, ed 6, Philadelphia, 1998, WB Saunders.)
As discussed earlier, normal meiosis requires pairing of homologous chromosomes followed by recombination. The autosomes and the X chromosomes in females present no unusual difficulties in this regard; but what of the X and Y chromosomes during spermatogenesis? Although the X and Y chromosomes are different and are not homologues in a strict sense, they do have relatively short identical segments at the ends of their respective short arms (Xp and Yp) and long arms (Xq and Yq) (see Chapter 6). Pairing and crossing over occurs in both regions during meiosis I. These homologous segments are called pseudoautosomal to reflect their autosome like pairing and recombination behavior, despite being on different sex chromosomes.
Oogenesis
Whereas spermatogenesis is initiated only at the time of puberty, oogenesis begins during a female’s development as a fetus (Fig. 2). The ova develop from oogonia, cells in the ovarian cortex that have descended from the primordial germ cells by a series of approximately 20 mitoses. Each oogonium is the central cell in a developing follicle. By approximately the third month of fetal development, the oogonia of the embryo have begun to develop into primary oocytes, most of which have already entered prophase of meiosis I. The process of oogenesis is not synchronized, and both early and late stages coexist in the fetal ovary. Although there are several million oocytes at the time of birth, most of these degenerate; the others remain arrested in prophase I for decades. Only approximately 400 eventually mature and are ovulated as part of a woman’s menstrual cycle.
Fig2. Human oogenesis and fertilization in relation to the two meiotic divisions. The primary oocytes are formed prenatally and remain suspended in prophase of meiosis I for years until the onset of puberty. An oocyte completes meiosis I as its follicle matures, resulting in a secondary oocyte and the first polar body. After ovulation, each oocyte continues to metaphase of meiosis II. Meiosis II is completed only if fertilization occurs, resulting in a fertilized mature ovum and the second polar body.
After a woman reaches sexual maturity, individual follicles begin to grow and mature, and a few (on average one per month) are ovulated. Just before ovulation, the oocyte rapidly completes meiosis I, dividing in such a way that one cell becomes the secondary oocyte (an egg or ovum), containing most of the cytoplasm with its organelles; the other cell becomes the first polar body (see Fig. 2). Meiosis II begins promptly and proceeds to the metaphase stage during ovulation, where it halts again, only to be completed if fertilization occurs.
Fertilization
Fertilization of the egg usually takes place in the fallopian tube within a day or so of ovulation. Although many sperm may be present, the penetration of a single sperm into the ovum sets up a series of biochemical events that usually prevent the entry of other sperm.
Fertilization is followed by the completion of meiosis II, with the formation of the second polar body (see Fig. 2). The chromosomes of the now-fertilized egg and sperm form pronuclei, each surrounded by its own nuclear membrane. It is only upon replication of the parental genomes after fertilization that the two haploid genomes become one diploid genome within a shared nucleus. The diploid zygote divides by mitosis to form two diploid daughter cells, the first in the series of cell divisions that initiate the process of embryonic development.
Although development begins at the time of conception, with the formation of the zygote, in clinical medicine the stage and duration of pregnancy are usually measured as the “menstrual age,” dating from the beginning of the mother’s last menstrual period, typically approximately 14 days before conception.
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