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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

Putative mechanism of the DSB-independent surveillance system for synapsis during meiosis I. (A) Surveillance system for detecting extensive synapsis failure that is typically observed in Spo11 deficiency. (B) Surveillance system for detecting partial synapsis failure that is typically observed in translocation carriers.
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Figure 4: Putative mechanism of the DSB-independent surveillance system for synapsis during meiosis I. (A) Surveillance system for detecting extensive synapsis failure that is typically observed in Spo11 deficiency. (B) Surveillance system for detecting partial synapsis failure that is typically observed in translocation carriers.

Mentions: Next, we set out to determine what mechanism triggers apoptosis at the Hormad1-dependent pachytene checkpoint for synapsis that operates both in males and females. One plausible idea is the transcriptional silencing of autosomes via MSUC. As mentioned above, Spo11 deficiency induces the formation of the pseudo-sex body, within which the transcription of autosomes might be silenced, possibly leading to cell death. Hormad1 deficiency abrogates formation of the pseudo-sex body in Hormad1/Spo11 double-knockout females (Daniel et al., 2011; Kogo et al., 2012). Therefore, MSUC within the pseudo-sex body might be the cause of cell death in Spo11-deficient mice and, furthermore, it appears to be Hormad1-dependent. On the other hand, another pathway that is not involved in MSUC also underlies the etiology of Hormad1-dependent cell death in synapsis failure (Kouznetsova et al., 2009). We found that Hormad1 is abundant at the unsynapsed chromosomes axes and highly phosphorylated in Spo11-deficient mice (Kogo et al., 2012). We propose the hypothesis that extensive asynapsis activates the pachytene checkpoint signaling pathway via the phosphorylation of Hormad1, thereby leading to stage IV apoptosis in both males and females. A possible mechanism is illustrated in Figure 4A.


Failure of homologous synapsis and sex-specific reproduction problems.

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

Putative mechanism of the DSB-independent surveillance system for synapsis during meiosis I. (A) Surveillance system for detecting extensive synapsis failure that is typically observed in Spo11 deficiency. (B) Surveillance system for detecting partial synapsis failure that is typically observed in translocation carriers.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 4: Putative mechanism of the DSB-independent surveillance system for synapsis during meiosis I. (A) Surveillance system for detecting extensive synapsis failure that is typically observed in Spo11 deficiency. (B) Surveillance system for detecting partial synapsis failure that is typically observed in translocation carriers.
Mentions: Next, we set out to determine what mechanism triggers apoptosis at the Hormad1-dependent pachytene checkpoint for synapsis that operates both in males and females. One plausible idea is the transcriptional silencing of autosomes via MSUC. As mentioned above, Spo11 deficiency induces the formation of the pseudo-sex body, within which the transcription of autosomes might be silenced, possibly leading to cell death. Hormad1 deficiency abrogates formation of the pseudo-sex body in Hormad1/Spo11 double-knockout females (Daniel et al., 2011; Kogo et al., 2012). Therefore, MSUC within the pseudo-sex body might be the cause of cell death in Spo11-deficient mice and, furthermore, it appears to be Hormad1-dependent. On the other hand, another pathway that is not involved in MSUC also underlies the etiology of Hormad1-dependent cell death in synapsis failure (Kouznetsova et al., 2009). We found that Hormad1 is abundant at the unsynapsed chromosomes axes and highly phosphorylated in Spo11-deficient mice (Kogo et al., 2012). We propose the hypothesis that extensive asynapsis activates the pachytene checkpoint signaling pathway via the phosphorylation of Hormad1, thereby leading to stage IV apoptosis in both males and females. A possible mechanism is illustrated in Figure 4A.

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