Obstructive azoospermia (OA) accounts for approximately 40% of males who suffer from azoospermia of male infertility. Currently, available treatment for OA consists of reproductive tract surgical reconstruction and sperm retrieval from the testis. However, both treatments result in low fertility compared to normal pregnancy, and the main reason remains largely unknown. Previous studies have shown that the quality of sperm retrieved from OA patients is poor compared with normal adult males but without an in-depth study. Herein, we generated a mouse OA model with vasectomy to evaluate sperm quality systematically. Our results showed that the testis had normal spermatogenesis but increased apoptotic activity in both OA patients and mice. More importantly, epididymal morphology was abnormal, with swollen epididymal tubules and vacuole-like principal cells. Especially, sperm retrieved from the epididymis of OA mice showed poor motility and low fertilization ability in vitro. Using mass spectrometry in epididymal fluid, we found differences in the expression of key proteins for sperm maturation, such as Angiotensinogen (AGT), rhophilin-associated tail protein 1 (ROPN1), NPC intracellular cholesterol transporter 2 (NPC2), and prominin 1 (PROM1). Furthermore, our results demonstrated that AGT, secreted by epididymal principal cells, could regulate sperm motility by managing PKCα expression to modify sperm phosphorylation. In conclusion, our data evaluate sperm quality systematically in OA mice and contribute to the understanding between the sperm and epididymis, which may provide novel insight into treating male infertility.
Keywords: AGT; epididymal principal cells; male infertility; obstructive azoospermia; phosphorylation; sperm motility.
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