Skewed X inactivation and recurrent spontaneous abortion

Recent studies show that women experiencing recurrent spontaneous abortion exhibit nonrandom X-chromosome inactivation (XCI) more often than in contro ls. This suggests that genetic factors may be important in explaining the l osses in this subset of women. Nonetheless there are a number of possible e xplanations for this finding and the underlying causes may be heterogeneous . One hypothesis commonly cited is that a mutation on the X chromosome resu lts in both preferential inactivation of the mutated X as well as lethality of male embryos inheriting this mutated X. However, this hypothesis does n ot explain the increase in chromosome abnormalities observed in the karyoty ped losses from women with recurrent pregnancy loss and skewed XCI. This fi nding leads us to suggest that the mechanism involved may be associated wit h a reduction in number of ovarian follicles, either due to X mutations aff ecting oocyte atresia or a restriction in precursor pool size during develo pment.