Abstract

Sex ratio is an important indicator of reproductive health, and its skewing reflects disturbed embryonic development. This study focused on sex skewing, which has recently identified in human in vitro fertilization (IVF) babies. We reported herein that the skewed sex ratio in mouse IVF offspring was due to the impaired imprinted X chromosome inactivation via suppressing the ring finger protein 12 (Rnf12)/X-inactive specific transcript (Xist) pathway; the sex skewing can be corrected by overexpressing Rnf12 or by supplementation of retinoic acid in embryo culture medium. Hence, our study not only identified a major epigenetic error responsible for sex skewing in IVF offspring, but also implicated a potential strategy for preventing sex skewing and IVF-associated complications by targeting erroneous epigenetic modifications induced by IVF.