Meiotic Divisions: No Place for Gender Equality

Abstract

In multicellular organisms the fusion of two gametes with a haploid set of chromosomes leads to the formation of the zygote, the first cell of the embryo. Accurate execution of the meiotic cell division to generate a female and a male gamete is required for the generation of healthy offspring harboring the correct number of chromosomes. Unfortunately, meiosis is error prone. This has severe consequences for fertility and under certain circumstances, health of the offspring. In humans, female meiosis is extremely error prone. In this chapter we will compare male and female meiosis in humans to illustrate why and at which frequency errors occur, and describe how this affects pregnancy outcome and health of the individual. We will first introduce key notions of cell division in meiosis and how they differ from mitosis, followed by a detailed description of the events that are prone to errors during the meiotic divisions.

Loss and Rebirth of the Animal Microtubule Organizing Center: How Maternal Expression of Centrosomal Proteins Cooperates with the Sperm Centriole in Zygotic Centrosome Reformation

“…The sperm's morphology, in turn, is optimized for motility and fertilization: adjacent to the sperm nucleus sits the basal body (i.e., centriole) of the flagellum next to a number of mitochondria, while the actual cytoplasm is reduced to a minimum. In contrast, female reproductive cells usually stay immobile and establish a very large cytoplasm that dominates the first steps in development after fertilization . The large supply of female cytoplasm will carry the zygote through several rounds of cell divisions (“cleavage divisions”) right after fertilization, often in very short time.…”

Cyclin B3 promotes APC/C activation and anaphase I onset in oocyte meiosis

“…Under these conditions, germinal vesicle breakdown (GVBD, corresponding to nuclear envelope breakdown in mitosis) occurred with normal timing (within 90 min) and efficiency in Ccnb3 -/-oocytes ( Figure 1D), indicating that cyclin B3 is dispensable for entry into meiosis I. At ~7-10 hours in culture after entry into meiosis I, depending on the mouse strain, oocytes extrude a polar body (PB), indicating execution of the first division and exit from meiosis I [6,28]. Unlike for other aspects of female reproduction described above, Ccnb3 -/-mice displayed a highly penetrant defect at this stage of meiosis: oocytes failed to extrude a PB in most cyclin B3-deficient mice (50 out of 58 mice) ( Figure 1D).…”

“…In mice, as in other mammals, female meiosis initiates during fetal development [6,22]. Oocytes complete the chromosome pairing and recombination steps of meiotic prophase prior to birth, then enter a prolonged period of arrest (the dictyate stage) and coordinate with surrounding somatic cells during the first few days after birth to form follicles [6,22]. Primordial follicles are the resting pool of germ cells that will be recruited for further development and ovulation during the reproductive life of the animal [6,22].…”

“…Ordered CDK activity likewise governs progression through meiosis: chromosome condensation, congression, and alignment require a rise in cyclin B-CDK1 activity, then anaphase onset and chromosome segregation are driven by sudden inactivation of cyclin B-CDK1 by the anaphase promoting complex/ cyclosome (APC/C), an E3 ubiquitin ligase that targets substrates for degradation by the 26S proteasome [5]. Cyclin B-CDK1 activity re-accumulates following its depletion, but meiotic cells have the challenge of not inducing DNA replication during the period of low cyclin B-CDK1 activity between meiosis I and II [6,7]. The roles of specific cyclins in shaping CDK oscillations and thus in determining the orderly progression of meiosis remain poorly understood, particularly in mammalian oocytes.…”

“…Oocytes complete the chromosome pairing and recombination steps of meiotic prophase prior to birth, then enter a prolonged period of arrest (the dictyate stage) and coordinate with surrounding somatic cells during the first few days after birth to form follicles [6,22]. Primordial follicles are the resting pool of germ cells that will be recruited for further development and ovulation during the reproductive life of the animal [6,22]. Ovary sections from Ccnb3 -/-females showed abundant oocytes in primordial and growing follicles at 2-3 months of age, and were quantitatively and morphologically indistinguishable from littermate controls ( Figure 1C).…”