Primary and motile cilia in the efferent ductules: a role for IFT88 in maintaining male fertility.

The efferent ductules are male reproductive tubules that support fertility by reabsorbing fluid and transporting sperm from testis to the epididymis. They are lined with multiciliated cells (MCCs) and reabsorptive primary ciliated cells (RPCCs). While motile cilia drive fluid flow, the contribution of primary cilia and their interaction with motile cilia remain unclear. To address this, we generated a conditional Ift88 knockout (cKO) to disrupt both primary and motile cilia in the efferent ductule epithelium. Loss of IFT88 caused shortened cilia, epithelial disorganization, and impaired fluid homeostasis. Ift88 cKO males developed early-onset infertility with luminal dilation, sperm agglutination, and obstructive azoospermia. We observed reduced ESR1 expression in proximal ductules with disruption of estrogen-dependent signaling pathways. We propose that primary cilia maintain trafficking and glycosylation machinery required for correct AQP1 localization, a key estrogen-regulated mediator of fluid reabsorption in RPCCs, as well as for postnatal epithelial maturation from a predominantly secretory to a reabsorptive state. These results identify IFT88-dependent ciliogenesis as essential for efferent ductule architecture, luminal homeostasis, and male fertility.