Efficient phagocytic clearance of apoptotic spermatogenic cells and residual bodies (RBs) by Sertoli cells (SCs) is crucial for functional mature spermatogenesis. However, little is known about the molecular mechanisms underlying this SCs function. Herein, we reported for the first time that SCs-expressing metastasis associated protein 2 (Mta2), a chromatin modifier playing a critical role in modifying DNA accessibility for transcriptional regulation, was steadily up-regulated when SCs were co-cultured with RBs. The most efficient stimulatory substrates for the inducement of phagocytosis-elicited Mta2 expression were RBs and fragments from apoptotic spermatocytes. Furthermore, one major result of this response is the transcriptional repression of follicle-stimulating hormone receptor gene (Fshr) expression during phagocytosis, which should lead to a low level of circulated FSH because effects of FSH on spermatogenesis is fundamentally regulated by the down-regulation of Fshr after exposure to FSH. Given that high concentration of circulated FSH inhibits SCs phagocytic activity and impairment of MTA2 expression is associated with the abnormal high level of serum FSH, our present results suggest that the FSH/MTA2/ Fshr cascade may serve as an indispensable negative feedback mechanism to help to maintain low level of circulated FSH, which is required for the normal occurrence of SCs phagocytosis. (C) 2014 Elsevier Inc. All rights reserved.