• PMID: 8622925
• Gene Name: HSPA1A
• Condition: Associated with failed meiosis, germ cell apoptosis, and male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Associated with failed meiosis, germ cell apoptosis, and male infertility

Targeted gene disruption of Hsp70-2 results in failed meiosis, germ cell apoptosis, and male infertility

Dix DJ, Allen JW, Collins BW, Mori C, Nakamura N, Poorman-Allen P, Goulding EH, Eddy EM.

In addition to the five 70-kDa heat shock proteins (HSP70) common to germ cells and somatic tissues of mammals, spermatogenic cells synthesize HSP70-2 during meiosis. To determine if this unique stress protein has a critical role in meiosis, we used gene-targeting techniques to disrupt Hsp70-2 in mice. Male mice homozygous for the mutant allele (Hsp70-2 -/-) did not synthesize HSP70-2, lacked postmeiotic spermatids and mature sperm, and were infertile. However, neither meiosis nor fertility was affected in female Hsp70-2 -/- mice. We previously found that HSP70-2 is associated with synaptonemal complexes in the nucleus of meiotic spermatocytes from mice and hamsters. While synaptonemal complexes assembled in Hsp70-2 -/- spermatocytes, structural abnormalities became apparent in these cells by late prophase, and development rarely progressed to the meiotic divisions. Furthermore, analysis of nuclei and genomic DNA indicated that the failure of meiosis in Hsp70-2 -/- mice was coincident with a dramatic increase in spermatocyte apoptosis. These results suggest that HSP70-2 participates in synaptonemal complex function during meiosis in male germ cells and is linked to mechanisms that inhibit apoptosis. FAU - Dix, D J AU - Dix DJ AD - Reproductive Toxicology Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. FAU - Allen, J W AU - Allen JW FAU - Collins, B W AU - Collins BW FAU - Mori, C AU - Mori C FAU - Nakamura, N AU - Nakamura N FAU - Poorman-Allen, P AU - Poorman-Allen P FAU - Goulding, E H AU - Goulding EH