Region-specific roles of oviductal motile cilia in oocyte/embryo transport and fertility†.

Abstract

The physiological and clinical importance of motile cilia in reproduction is well recognized; however, the specific role they play in transport through the oviduct and how ciliopathies lead to subfertility and infertility are still unclear. The contribution of cilia beating, fluid flow, and smooth muscle contraction to overall progressive transport within the oviduct remains under debate. Therefore, we investigated the role of cilia in the oviduct transport of preimplantation eggs/embryos using a combination of genetic and advanced imaging approaches. We show that the region of the oviduct where cumulus-oocyte complex circling occurs, around the time of fertilization, is correlated with asymmetrical mucosal fold arrangement and non-radially distributed ciliated epithelium. Our results suggest that motile cilia, as well as mucosal fold asymmetry, may contribute to the local flow fields that help steer luminal contents away from the epithelial walls. We also present, in vivo, volumetric evidence of delayed egg transport in a genetic mouse model with disrupted motile cilia function in the female reproductive system. Females with Dnah5 deleted in the oviduct epithelium are subfertile and demonstrate disrupted motile cilia activity within the oviduct mucosa. Fifty percent of Dnah5 mutant females have delayed egg transport where cumulus-oocyte complexes did not progress to the ampulla at the expected time point and remained within the ovarian bursa. The integration of advanced imaging with genetic dysfunction of motile cilia provides valuable insights into oviductal transport. Potentially, these data could be valuable for better understanding and management of tubal pathologies and human infertility.