Oligo-astheno-teratozoospermia in mice lacking Cnot7, a regulator of retinoid X receptor beta

Abstract

Spermatogenesis is a complex process that involves cooperation of germ cells and testicular somatic cells. Various genetic disorders lead to impaired spermatogenesis, defective sperm function and male infertility. Here we show that Cnot7-/- males are sterile owing to oligo-astheno-teratozoospermia, suggesting that Cnot7, a CCR4-associated transcriptional cofactor, is essential for spermatogenesis. Maturation of spermatids is unsynchronized and impaired in seminiferous tubules of Cnot7 -/- mice. Transplantation of spermatogonial stem cells from male Cnot7-/- mice to seminiferous tubules of Kit mutant mice (Kit W/W-v) restores spermatogenesis, suggesting that the function of testicular somatic cells is damaged in the Cnot7-/- condition. The testicular phenotypes of Cnot7-/- mice are similar to those of mice deficient in retinoid X receptor beta (Rxrb). We further show that Cnot7 binds the AF-1 domain of Rxrb and that Rxrb malfunctions in the absence of Cnot7. Therefore, Cnot7 seems to function as a coregulator of Rxrb in testicular somatic cells and is thus involved in spermatogenesis.