Telomere clustering is a widespread phenomenon among eukaryotes. However, the molecular mechanisms that regulate formation of telomere clustering in mammalian meiotic prophase I, are still largely unknown. Here, we show that CDK2, especially p39(cdk2), as a potential meiosis-specific connector interaction with SUN1 mediates formation of telomere clustering during mouse meiosis. The transition from CDK2 to p-CDK2 also regulates the progression from homologous recombination to desynapsis by interacting with MLH1. In addition, disappearance of CDK2 on the telomeres and of p-CDK2 on recombination sites, were observed in Sun1(-/-) mice and in pachytene-arrested hybrid sterile mice (pwk×C57BL/6 F1), respectively. These results suggest that transition from CDK2 to p-CDK2 plays a critical role for regulating meiosis progression.

Incompatibilities in interspecific hybrids, such as reduced hybrid fertility and lethality, are common features resulting from reproductive isolation that lead to speciation. Subspecies crosses of house mice produce offspring in which one sex is infertile or absent, yet the molecular mechanisms of hybrid sterility are poorly understood. In this study, we observed extensive asynapsis of chromosomes and disturbance of the sex body in pachytene spermatocytes of sterile F1 males (PWK/Ph female × C57BL/6J male). We report the high-confidence identification of 4005 proteins in the pachytene spermatocytes of fertile F1 males (PWK/Ph male × C57BL/6J female) and sterile F1 males (PWK/Ph female × C57BL/6J male), of which 215 were upregulated and 381 were downregulated. Bioinformatics analysis of the proteome led to the identification of 43 and 59 proteins known to be essential for male meiosis and spermatogenesis in mice, respectively. Characterization of the proteome of pachytene spermatocytes associated with hybrid male sterility provides an inventory of proteins that is useful for understanding meiosis and the mechanisms of hybrid male infertility.

In mammalian meiosis, the X and Y chromosomes are largely unsynapsed and transcriptionally silenced during the pachytene stage of meiotic prophase (meiotic sex chromosome inactivation), forming a specialized nuclear territory called sex or XY body. An increasing number of proteins and noncoding RNAs were found to localize to the sex body and take part in influencing expression of sex chromosome genes. Cyclin-dependent kinase 2 (Cdk2 (-/-)) spermatocytes show incomplete sex chromosome pairing. Here, we further showed that phosphorylation of CDK2 isoform 1 (p-CDK2(39) [39 kDa]) on threonine 160 localizes to the sites of asynapsis and the sex body, interacting with phosphorylated gamma-H2AX. Meanwhile, p-CDK2(39) is frequently mislocalized throughout the sex body, and meiotic sex chromosome inactivation is disrupted in PWK×C57BL/6J hybrid mice. Furthermore, pachytene spermatocytes treated with mevastatin (an inhibitor of p-CDK2) showed overexpression of sex chromosome-linked genes. Our results highlight an important role for p-CDK2(39) in influencing silencing of the sex chromosomes during male meiosis by interacting with gamma-H2AX.

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The DDK syndrome is known as the polar-lethal embryonic death that occurs at the morula-blastocyst stage when female mice of the DDK strain are mated with males from many other inbred strains (alien males). Embryonic death is interpreted to be caused by incompatibility between a DDK oocyte factor and the product from male pronucleus, both of which map to the Om locus on mouse chromosome 11. We compared development of DDK ×DDK embryos (high viability) and DDK × BALB/c embryos (low viability) before the morula stage (as 2 cell, 4 cell and 8 cell), there was no any morphological manifestations of DDK syndrome are observed. To make sure if the transcripts that are differentially in the DDK ×BALB/c embryos, we selected a series reference genes such as proto-oncogenes, growth factors, and growth and apoptosis genes and confirmed by quantitative RT-PCR that numbers of genes in those stages are down regulated in the DDK ×BALB/c embryos. However, except the LIF (leukemia inhibitory factor) was negative expressed and the other genes all detected in three stages. The expression of EGF (epidermal growth factor), EGF-R (epidermal growth factor receptor), Bcl-2 were significant variations (P< 0.01) at the early 4 cell and 8 cell stage, and also the test was significant variations (P<0.01) for the Mcl-1 at all the three stages. Our results indicate that the Om was effected the low-expression of functional genes indirectly to induce embryos destined to die of DDK syndrome and that the embryonic death observed is result of the regulation of multiple genes. Keywords-mouse eimplantation embry; polar-lethal embryonic death; ovum mutant or Om; DDK syndrome I.978-1-4244-9171-1/11/$26.00 ©2011 IEEE