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Aneuploidy in Human Oocytes and Preimplantation Embryos
Published in Carlos Simón, Carmen Rubio, Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
The loss of cohesion and structural integrity of bivalent chromosomes are age-dependent and is one manifestation of “chromosomal aging” in human oocytes (83–85). However, the molecular mechanism underlying loss of cohesion is currently not known. Studies from rodents suggest that the loading of cohesin complexes may be restricted to fetal development (86–88) and subsequently affected during the extended dictyate arrest (89,90). Intriguingly, SMC1β, a meiosis-specific component of meiotic cohesin complexes is haploinsufficient for maintaining the bivalent configuration in mouse oocytes (91,92). Whether depletion of meiotic cohesin complexes underlies cohesion loss in human oocytes is not clear, since loss of cohesin staining does not appear to preferentially affect the chromosomes that have lost their bivalent structure (93). Since only a proportion of cohesin complexes are thought to mediate sister chromatid cohesion in mitotic cells (94,95), it is possible that the cohesive function of the cohesin complexes, an acetylated form of SMC3, may be affected during the extended dictyate arrest. Common genetic variants in cohesin genes have been linked to trisomy 21 risk in a recent genome-wide association study (96).
Reproductive System and Mammary Gland
Published in Pritam S. Sahota, James A. Popp, Jerry F. Hardisty, Chirukandath Gopinath, Page R. Bouchard, Toxicologic Pathology, 2018
Justin D. Vidal, Charles E. Wood, Karyn Colman, Katharine M. Whitney, Dianne M. Creasy
The development of the female reproductive tract begins with formation of the PGC in the yolk sac. The PGC subsequently migrate to and colonize the genital ridge where they stimulate splanchnic mesoderm of the genital ridge to develop into the gonad. In females, failure of PGC to colonize the genital ridge results in a small ovary containing only stromal elements in the adult (McLaren 1991). In the developing ovary, the PGC continue to proliferate, develop into oogonia and enter into meiosis I, arresting in the dictyate stage before birth. In the absence of Sry expression (which activates the male differentiation pathway), the secondary sex cords develop in the developing gonad, giving rise to pre-granulosa cells that associate with the oocytes to form primordial follicles (McLaren 1991; Pepling 2006). A review of ovarian development and differentiation, with an emphasis on current knowledge of the molecular mechanisms associated with these processes, has been described elsewhere (Edson et al. 2009). In the absence of androgenic stimulation, the mesonephric (Wolffian) duct degenerates and the upper portion of the female reproductive tract (uterine tubes, uterus, cervix, and anterior vagina) develops from the paramesonephric (Müllerian) duct. The lower portion of the tract, including the posterior vagina, vulva, and clitoris are derived from the urogenital sinus.
Heterologous Pairing and Fertility in Humans
Published in Christopher B. Gillies, Fertility and Chromosome Pairing: Recent Studies in Plants and Animals, 2020
In the human female, however, the germ cells or oogonia within the fetal ovary continue their development, increasing greatly in number by mitotic division. In the human female, approximately 7 million oocytes are present at midterm, but decline in number to about 2 million by birth.34 The elimination of so many oocytes by degeneration or atresia seems quite a drastic selection when we consider that only 400 to 500 oocytes will finally be ovulated. After oogonia enter the final mitotic interphase, they proceed through a premeiotic DNA synthesis stage and enter the prophase of meiosis as early as week 11 of gestation.35 By birth, they will have entered a resting stage known as dictyotene, which is characterized by highly diffuse chromosomes. The important feature of human female meiosis, then, is that synapsis and recombination will have taken place by birth. Although the dictyotene stage has been termed a resting stage, just after birth, when the oocyte and the follicle that it is enclosed in are growing in size, active replication of RNA occurs, the chromosomes now having a lampbrush-like structure.36 Such RNA may be laid down for the subsequent stages of meiosis and early stages of embryogenesis. Only later, as the granulous cells of the follicle become active, supplying maternal proteins to the ooplasm, can the dictyate nucleus be said to be in the resting state. This stage persists until puberty in the female, at approximately 12 years of age. Follicular maturation then takes place and, with cyclical ovulation, a certain percentage of oocytes are deemed mature enough to respond to pituitary gonadotrophin. Some follicles then respond to follicle stimulating hormone and undergo final maturation, and are induced to move out of the dictyate stage and progress through diplotene and metaphase I under the influence of luteinizing hormones (LH). This LH peak is about 36 h before ovulation in the human female. The first meiotic division occurs with the formation of the metaphase II chromosomes and the first polar body. This is the stage where meiotic nondisjunction can first occur, due to the failure of bivalent separation or random segregation of univalent chromosomes. There may be total nondisjunction leading to diploid metaphase II oocytes which, on fertilization, would yield triploid fetuses. The secondary oocyte then arrests at metaphase II and it is at this point that ovulation takes place. No further development occurs unless fertilization takes place, when the second meiotic division occurs with the separation of chromatids and second polar body extrusion. This is the second stage where meiotic nondisjunction can occur.
Oocyte Survival and Development during Follicle Formation and Folliculogenesis in Mice Lacking Aromatase
Published in Endocrine Research, 2022
Jessica M. Toothaker, Kristen Roosa, Alexandra Voss, Suzanne M. Getman, Melissa E. Pepling
The process of oocyte development and follicle formation begins in the fetus with the migration of primordial germ cells to the developing ovary.2 The germ cells then undergo several rounds of mitosis, and during this time they are referred to as oogonia. Groups of oogonia, connected by intracellular bridges, are formed as the result of incomplete cytokinesis after each round of mitosis.3 These groups of oogonia are referred to as germ cell cysts and become oocytes when they enter meiosis.4,5 In mice, cysts first fragment into smaller cysts which then reassociate so that clusters contain some oocytes connected by intercellular bridges and other oocytes associated by aggregation.6 During this time, the oocytes progress through the first stages of meiotic prophase I and become arrested at an extended diplotene stage called dictyate.7,8 Beginning at 17.5 days post coitum (dpc) the cells separate and individual oocytes become surrounded with pregranulosa cells.9 This process is accompanied by apoptosis of several oocytes from each cyst.10 There is evidence that the oocytes that are lost serve to support or “nurse” the surviving oocytes.11 Those that remain become enclosed by pregranulosa cells to make up the ovarian reserve consisting of diplotene-arrested oocytes housed within primordial follicles.12 Despite the significance of this process for female fertility, the precise mechanisms that regulate cyst breakdown and follicle formation in mammals remain poorly understood.
Genetic variations as molecular diagnostic factors for idiopathic male infertility: current knowledge and future perspectives
Published in Expert Review of Molecular Diagnostics, 2021
Mohammad Karimian, Leila Parvaresh, Mohaddeseh Behjati
A study in 2000 by Baudat et al. showed that disruption of Spo11 in mice has led to severe gonadal abnormalities owing to defective meiosis and apoptosis of spermatocytes during the initial prophase. Eggs reach the diplotene/dictyate stage almost normally, but most of them die immediately after birth. Spo11-/- myocytes also showed synaptic defects of homologous chromosomes [84]. In another study, it was found that deletion of Spo11 caused significant changes in the expression of genes involved in meiosis recombination (Hop2, Brca2, Mnd1, FancG) and at the miotic checkpoints (cyclin B2, Cks2) without any impact on the genes encoding the protein components of the synaptonemal complex. Finally, they discovered unknown genes that are affected by the Spo11 disrupted gene that could therefore be specifically involved in meiosis and spermatogenesis [85]. The details of the important genetic polymorphisms of the aforementioned genes as well as some characteristics including pathological effects, sample size, and ethnicity of the studied population are summarized in Table 1.
The existence and potential of germline stem cells in the adult mammalian ovary
Published in Climacteric, 2019
The mammalian ovary is a highly dynamic organ that undergoes many structural and functional changes as it fulfills its two major roles of producing female gametes and the synthesis of sex steroids. In the human ovary, germ cells (oocytes) are formed during fetal life and they are enclosed within somatic cells (granulosa cells) to form primordial follicles. The primordial follicles consist of an oocyte, arrested at the diplotene (dictyate) stage of prophase I of meiosis, surrounded by a few flattened somatic cells (granulosa cells). For many years it has been assumed that there is a limited period during which oocytes can be formed and that the adult ovary has no capacity for germ cell renewal, and therefore primordial follicles represent a pool of oocytes that must last the woman throughout her reproductive lifespan (Figure 1).