Cilia are evolutionarily conserved microtubule-based structures that perform diverse biological functions. Cilia are assembled on basal bodies and anchored to the plasma membrane via distal appendages. In the male reproductive tract, multicilia in efferent ducts (EDs) move in a whip-like motion to prevent sperm agglutination. Previously, we demonstrated that the distal appendage protein CEP164 recruits Chibby1 (Cby1) to basal bodies to facilitate basal body docking and ciliogenesis. Mice lacking CEP164 in multiciliated cells (MCCs) (FoxJ1-Cre;CEP164fl/fl) show a significant loss of multicilia in the trachea, oviduct, and ependyma. In addition, we observed male sterility; however, the precise role of CEP164 in male fertility remained unknown. Here, we report that the seminiferous tubules and rete testis of FoxJ1-Cre;CEP164fl/fl mice exhibit substantial dilation, indicative of dysfunctional multicilia in the EDs. We found that multicilia were hardly detectable in the EDs of FoxJ1-Cre;CEP164fl/fl mice although FoxJ1-positive immature cells were present. Sperm aggregation and agglutination were commonly noticeable in the lumen of the seminiferous tubules and EDs of FoxJ1-Cre;CEP164fl/fl mice. In FoxJ1-Cre;CEP164fl/fl mice, the apical localization of Cby1 and the transition zone marker NPHP1 was severely diminished, suggesting basal body docking defects. TEM analysis of EDs further confirmed basal body accumulation in the cytoplasm of MCCs. Collectively, we conclude that male infertility in FoxJ1-Cre;CEP164fl/fl mice is caused by sperm agglutination and obstruction of EDs due to loss of multicilia. Our study, therefore, unravels an essential role of the distal appendage protein CEP164 in male fertility.
Mohammed Hoque, Danny Chen, Rex A Hess, Feng-Qian Li, and Ken-Ichi Takemaru
Brooke E Barton, Gerardo G Herrera, Prashanth Anamthathmakula, Jenna K Rock, Anna M Willie, Emily A Harris, Ken-Ichi Takemaru, and Wipawee Winuthayanon
The oviduct (known as the fallopian tube in humans) is the site for fertilization and pre-implantation embryo development. Female steroid hormones, estrogen and progesterone, are known to modulate the morphology and function of cells in the oviduct. In this review, we focus on the actions of estrogen and progesterone on secretory, ciliated, and muscle cell functions and morphologies during fertilization, pre-implantation embryo development, and embryo transport in humans, laboratory rodents and farm animals. We review some aspects of oviductal anatomy and histology and discuss current assisted reproductive technologies (ARTs) that bypass the oviduct and their effects on embryo quality. Lastly, we review the causes of alterations in secretory, ciliated, and muscle cell functions that could result in embryo transport defects.