Absence of p53 and FasL has sexually dimorphic effects on both development and reproduction

Reproduction and development are highly dependent on apoptosis to balance the proliferation that necessarily occurs during these processes. How the absence of two apoptotic factors in mice would affect reproduction and development was examined. Given previous reports of increased neural tube defects in p53-/- female fetuses, decreased fertility in gld female mice, and altered spermatogenesis in both p53 and gld male mice, the possibility that these phenotypes might be enhanced by the elimination of a second apoptotic factor was investigated. The reproductive vigor and the health of offspring were monitored during the production of the new double-deficient strain (FasL-/-p53-/-) for any changes from the reported phenotypes. Thus, any unusual phenotypes that could lead to new models for studying mechanisms of health and disease would be identified. Double-deficient male offspring appeared healthy and occurred at expected frequencies. Additionally, spermatogenesis and male fertility were unaffected by the gene deficiencies. On the other hand, FasL+/+p53-/- and FasL-/-p53-/- female mice were susceptible to increased malformations and post-natal death. These abnormalities were consistent with previous reports of neural tube defects in p53-/- female mice. Fertility rates were also significantly decreased in p53-/- female mice that lived to be adults, an observation not previously reported. Finally, the absence of both FasL- and p53 led to dystocia in pregnant female mice, suggesting that the two genes play complementary roles in parturition. Therefore, although male mouse development and reproduction remained unaffected by p53 and FasL deficiencies, female mouse development was adversely affected by the absence of p53, and no live litters were born to female mice with the combined absence of both FasL and p53. In this report, we suggest a potential mechanism involving corpora luteal regression to explain this defect in parturition in Fast-/-p53-/- female mice.