TMC7 is required for spermiogenesis and male fertility by regulating TGN-derived vesicles.

Infertility affects 10-12 % of couples worldwide, 50 % of which are male. Abnormal spermatogenesis is among the main causes of male infertility. We were curious about the possible role of transmembrane channel-like protein 7 (TMC7) in spermatogenesis because of its aberrant expression in several male infertility patients. In this study, we found that deletion of Tmc7, which is highly expressed during spermiogenesis, causes a human oligoasthenoteratozoospermia (OAT)-like phenotype in male mice. By histological analysis, TEM, RNA-seq and library-free data-independent acquisition mass spectrometry (DIA-MS) of TMC7-null mouse testes, we found that Tmc7 deletion caused abnormal swelling of trans-Golgi network (TGN) vesicles in elongated spermatids. Further immunofluorescence localization analysis revealed that these vesicles were defined by synaptophysin-like 1 (SYPL1). In addition, TMC7 may act as a potential chloride transport channel to regulate the size of transport vesicles. In conclusion, this study demonstrated that TMC7 is essential for male fertility and may be used as a potential protein for the identification and recognition of OAT. On the other hand, TMC7 may be a potential male contraceptive target.