PARENT SESSION
SLIDE SESSION 5: REGULATION OF MEIOSIS
Chairs: Stephen Downs, Sue Varmuza, Michele Calder (Trainee)
Univ Ottawa-Monpetit 202
2:30 PM-4:30 PM

INCREASED RATE OF MEIOSIS IN A MURINE MODEL OF MALE INFERTILITY - CAN IT EXPLAIN INCREASED ANEUPLOIDY?

Varmuza, Sue¹, ¹

ABSTRACT- Loss of PP1c causes male sterility with features reminiscent of OAT (oligoasthenoteratozoospermia) in humans. PP1c encodes a protein phosphatase catalytic subunit that is required for completion of spermiogenesis. The histopathology is consistent with a defect in either completion of cytodifferentiation of haploid sperm, or in maintenance of seminiferous epithelial integrity leading to premature release of immature spermatids. We have demonstrated that mutant spermatids display increased levels of aneuploidy when compared with wild type and heterozygous littermates (Oppedisano et al, submitted). This suggests that meiotic divisions are adversely affected by the mutation, either directly through a PP1c specific function in meiotic cells, or indirectly through abnormal responses to a defective testicular environment. While the sterility in PP1c mutant males is fully penetrant (all males are completely sterile), aneuploidy levels vary among mutant males from severe to almost indistinguishable from wild type, lending support to the latter hypothesis. In the present series of experiments, recombination frequency was assayed indirectly by recording the number and distribution of mlh foci in pachytene spermatocytes from mutant males, using an immunohistochemical approach. The rationale for these experiments is based on observations of altered recombination frequencies in aneuploid gametes in humans. I found that mutant pachytene spermatocytes display a higher frequency of mlh foci when compared with wild type and heterozygous littermates. Interestingly, mutant testes appear to proceed through meiosis more rapidly than wild type and heterozygous testes, as measured by the proportion of spermatocytes in testicular cell suspensions. This latter observation suggests that the increase in mlh foci, and possibly also in formation of aneuploid gametes, may be a function of the accelerated meiotic cell cycle.

KEY WORDS: infertility, aneuploidy, recombination, meiosis