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Failure of homologous synapsis and sex-specific reproduction problems.

Kurahashi H, Kogo H, Tsutsumi M, Inagaki H, Ohye T - Front Genet (2012)

Bottom Line: Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis.This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved.We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.

ABSTRACT
The prophase of meiosis I ensures the correct segregation of chromosomes to each daughter cell. This includes the pairing, synapsis, and recombination of homologous chromosomes. A subset of chromosomal abnormalities, including translocation and inversion, disturbs these processes, resulting in the failure to complete synapsis. This activates the meiotic pachytene checkpoint, and the gametes are fated to undergo cell cycle arrest and subsequent apoptosis. Spermatogenic cells appear to be more vulnerable to the pachytene checkpoint, and male carriers of chromosomal abnormalities are more susceptible to infertility. In contrast, oocytes tend to bypass the checkpoint and instead generate other problems, such as chromosome imbalance that often leads to recurrent pregnancy loss in female carriers. Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis. This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved. We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females.

No MeSH data available.


Related in: MedlinePlus

Autosome–sex body association in a translocation carrier. (A) Progression of prophase in meiosis I and the formation of the sex body in male mice. Prophase I begins during the leptotene stage when each chromosome begins condensation. The subsequent stage is the zygotene, which occurs when homologous chromosomes are paired and initiate SC formation. Because the chromosomal axes are stained with anti-SYCP3 (green) and the central elements of the SC are indicated with anti-SYCP1 staining (red), the regions that complete synapsis appear as yellow. During pachytene, all of the autosomes finish SC formation, while the male sex chromosomes cannot complete synapsis and remain green. The unsynapsed X and Y chromosomes are confined within the γH2AX-stained nuclear domain (blue). (B) Diagrams illustrating the autosome–sex body association. The upper panel shows sex body formation during normal spermatogenesis. Unsynapsed regions of the X and Y chromosomes are confined within the sex body (light blue). In male translocation carriers (lower panel), translocated chromosomes form quadrivalents (red and blue lines), which often have unsynapsed regions around the breakpoints, that become associated with the sex body.
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Figure 2: Autosome–sex body association in a translocation carrier. (A) Progression of prophase in meiosis I and the formation of the sex body in male mice. Prophase I begins during the leptotene stage when each chromosome begins condensation. The subsequent stage is the zygotene, which occurs when homologous chromosomes are paired and initiate SC formation. Because the chromosomal axes are stained with anti-SYCP3 (green) and the central elements of the SC are indicated with anti-SYCP1 staining (red), the regions that complete synapsis appear as yellow. During pachytene, all of the autosomes finish SC formation, while the male sex chromosomes cannot complete synapsis and remain green. The unsynapsed X and Y chromosomes are confined within the γH2AX-stained nuclear domain (blue). (B) Diagrams illustrating the autosome–sex body association. The upper panel shows sex body formation during normal spermatogenesis. Unsynapsed regions of the X and Y chromosomes are confined within the sex body (light blue). In male translocation carriers (lower panel), translocated chromosomes form quadrivalents (red and blue lines), which often have unsynapsed regions around the breakpoints, that become associated with the sex body.

Mentions: How are the chromosomes that undergo partial synapsis subsequently processed? A good example can help imagine this process: the behavior of sex chromosomes during male meiosis. In general, because male sex chromosomes are heteromorphic with small homologous regions known as pseudoautosomal regions at both chromosomal ends, they can make a pair and undergo HR to form the obligatory chiasma required for correct segregation during meiosis I. However, male sex chromosomes cannot be fully synapsed throughout the X or Y chromosome-specific regions and, instead, form a specialized nuclear territory known as the sex body or XY body (Figure 2A; Handel, 2004). The sex body is typically found at the periphery of the nucleus with synapsed chromosomal ends that are anchored to the nuclear lamina. In females, the meiotic stage progress from the pachytene to the subsequent diplotene stage after almost all of the chromosomes are fully synapsed and all of the DSBs are repaired. In contrast, because sex chromosomes cannot be fully synapsed and the DSB repair is delayed in males, the sex body is likely to mask the unsynapsed and unrepaired regions of the male sex chromosomes and facilitate cell cycle progression to the subsequent stage despite the presence of unsynapsed and unrepaired chromosomes.


Failure of homologous synapsis and sex-specific reproduction problems.

Kurahashi H, Kogo H, Tsutsumi M, Inagaki H, Ohye T - Front Genet (2012)

Autosome–sex body association in a translocation carrier. (A) Progression of prophase in meiosis I and the formation of the sex body in male mice. Prophase I begins during the leptotene stage when each chromosome begins condensation. The subsequent stage is the zygotene, which occurs when homologous chromosomes are paired and initiate SC formation. Because the chromosomal axes are stained with anti-SYCP3 (green) and the central elements of the SC are indicated with anti-SYCP1 staining (red), the regions that complete synapsis appear as yellow. During pachytene, all of the autosomes finish SC formation, while the male sex chromosomes cannot complete synapsis and remain green. The unsynapsed X and Y chromosomes are confined within the γH2AX-stained nuclear domain (blue). (B) Diagrams illustrating the autosome–sex body association. The upper panel shows sex body formation during normal spermatogenesis. Unsynapsed regions of the X and Y chromosomes are confined within the sex body (light blue). In male translocation carriers (lower panel), translocated chromosomes form quadrivalents (red and blue lines), which often have unsynapsed regions around the breakpoints, that become associated with the sex body.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3376420&req=5

Figure 2: Autosome–sex body association in a translocation carrier. (A) Progression of prophase in meiosis I and the formation of the sex body in male mice. Prophase I begins during the leptotene stage when each chromosome begins condensation. The subsequent stage is the zygotene, which occurs when homologous chromosomes are paired and initiate SC formation. Because the chromosomal axes are stained with anti-SYCP3 (green) and the central elements of the SC are indicated with anti-SYCP1 staining (red), the regions that complete synapsis appear as yellow. During pachytene, all of the autosomes finish SC formation, while the male sex chromosomes cannot complete synapsis and remain green. The unsynapsed X and Y chromosomes are confined within the γH2AX-stained nuclear domain (blue). (B) Diagrams illustrating the autosome–sex body association. The upper panel shows sex body formation during normal spermatogenesis. Unsynapsed regions of the X and Y chromosomes are confined within the sex body (light blue). In male translocation carriers (lower panel), translocated chromosomes form quadrivalents (red and blue lines), which often have unsynapsed regions around the breakpoints, that become associated with the sex body.
Mentions: How are the chromosomes that undergo partial synapsis subsequently processed? A good example can help imagine this process: the behavior of sex chromosomes during male meiosis. In general, because male sex chromosomes are heteromorphic with small homologous regions known as pseudoautosomal regions at both chromosomal ends, they can make a pair and undergo HR to form the obligatory chiasma required for correct segregation during meiosis I. However, male sex chromosomes cannot be fully synapsed throughout the X or Y chromosome-specific regions and, instead, form a specialized nuclear territory known as the sex body or XY body (Figure 2A; Handel, 2004). The sex body is typically found at the periphery of the nucleus with synapsed chromosomal ends that are anchored to the nuclear lamina. In females, the meiotic stage progress from the pachytene to the subsequent diplotene stage after almost all of the chromosomes are fully synapsed and all of the DSBs are repaired. In contrast, because sex chromosomes cannot be fully synapsed and the DSB repair is delayed in males, the sex body is likely to mask the unsynapsed and unrepaired regions of the male sex chromosomes and facilitate cell cycle progression to the subsequent stage despite the presence of unsynapsed and unrepaired chromosomes.

Bottom Line: Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis.This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved.We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Aichi, Japan.

ABSTRACT
The prophase of meiosis I ensures the correct segregation of chromosomes to each daughter cell. This includes the pairing, synapsis, and recombination of homologous chromosomes. A subset of chromosomal abnormalities, including translocation and inversion, disturbs these processes, resulting in the failure to complete synapsis. This activates the meiotic pachytene checkpoint, and the gametes are fated to undergo cell cycle arrest and subsequent apoptosis. Spermatogenic cells appear to be more vulnerable to the pachytene checkpoint, and male carriers of chromosomal abnormalities are more susceptible to infertility. In contrast, oocytes tend to bypass the checkpoint and instead generate other problems, such as chromosome imbalance that often leads to recurrent pregnancy loss in female carriers. Recent advances in genetic manipulation technologies have increased our knowledge about the pachytene checkpoint and surveillance systems that detect chromosomal synapsis. This review focuses on the consequences of synapsis failure in humans and provides an overview of the mechanisms involved. We also discuss the sexual dimorphism of the involved pathways that leads to the differences in reproductive outcomes between males and females.

No MeSH data available.


Related in: MedlinePlus