miR-34b/c-miR-449-dependent multiciliogenesis is essential for oocyte capture and efficient gamete and embryo transport in the oviduct. Mus musculus strain:C57

The mammalian oviduct has many functions that are essential for female fertility, including oocyte capture, gamete (sperm/oocyte) and embryo transport and nurturing. However, relative contributions to these functions by different cell types within the oviduct remain undefined. By inactivating two miRNA clusters (miR34b/c and miRNA-449), we generated knockout (KO) mice lacking motile cilia in the oviducts and this mouse model allowed us to unequivocally define the physiological role of oviductal motile cilia. Here we report that female mice without motile cilia in their oviducts failed to capture the ovulated oocytes, leading to female infertility. Sperm could still reach the ampulla region in the cilia-less oviducts, but the number of sperm was greatly reduced. Similarly, embryos manually transferred to the ampulla region of the cilia-less oviducts could reach the uterus for implantation, but the efficiency was much lower compare to wild type controls. Our data suggest that motile cilia in the fimbriae of the oviducts are essential for oocyte capture and thus female fertility, whereas motile cilia in the isthmus and ampulla regions of the oviducts appear to facilitate game/embryo transport, but are not absolutely required for female fertility. miR34b/c and miRNA-449 control normal multiciliogenesis in the oviductal epithelia by stabilizing their target genes, most of which are involved in multiciliogenesis.