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

TLDR

HSP70‑2 is a germ‑cell‑specific heat shock protein expressed during meiosis and associates with synaptonemal complexes in mouse spermatocytes. The authors disrupted Hsp70‑2 in mice using gene‑targeting to test its essential role in meiosis. Hsp70‑2 knockout males lacked postmeiotic spermatids, mature sperm, and were infertile, with meiotic arrest, synaptonemal complex defects, and heightened spermatocyte apoptosis, whereas females remained fertile.

Abstract

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.