Abstract
The aryl hydrocarbon receptor (AHR) is known for its roles in xenobiotic metabolism and essential physiologic processes such as cell growth, death, and differentiation. AHR is also an important regulator of male reproductive processes. However, no studies have characterized the consequences of loss of AHR in spermatogenesis. We used Ahr knockout (Ahr(-/-)) mice to assess the effects of loss of AHR on the architecture and gene expression of the seminiferous epithelium and functional sperm outcomes. The histopathological defects of the Ahr(-/-)seminiferous epithelium included vacuoles, multinucleated giant cells, hypocellularity with widened intercellular spaces, apical sloughing, and an excess number of retained elongated spermatids. Quantitative real-time PCR revealed significant down-regulation of Testin and Magea4, indicating Sertoli cell and spermatogenic dysregulation. Moreover, the reduced expression of Hspa2, Prm1, and Prm2 as well as decreased expression of Nrf2, Sod2, and Ucp2 suggested poorly remodeled germ cells with increased vulnerability to oxidative stress. In wild-type sperm, AHR protein was localized to the acrosome and the principal piece of the mature sperm flagellum. The in vitro fertilization rate was significantly lower with Ahr(-/-) sperm as compared to wild-type sperm, and there were morphologic abnormalities of the Ahr(-/-) sperm head and tail. Taken together, our data indicate that AHR plays an important role in normal sperm development.