GGA1 participates in spermatogenesis in mice under stress

Background. Infertility is recognized as a common and worrisome problem of human reproduction worldwide. Based on previous studies, male factors account for about half of all infertility cases. Exposure to environmental toxicants is an important contributor to male infertility. Bisphenol A (BPA) is the most prominent toxic environmental contaminant worldwide affecting the male reproductive system. BPA can impair the function of the Golgi apparatus which is important in spermatogenesis. GGA1 is known as Golgi-localized, gamma adaptin ear-containing, ARF-binding protein 1. Previously, it has been shown that GGA1 is associated with spermatogenesis in Drosophila, however, its function in mammalian spermatogenesis remains unclear. Methods. Gga1 knockout mice were generated using the CRISPR/Cas9 system. Gga1-/-male mice and wild-type littermates received intraperitoneal (i.p.) injections of BPA (40 mu g/kg) once daily for 2 weeks. Histological and immunofluorescence staining were performed to analyze the phenotypes of these mice. Results. Male mice lacking Gga1 had normal fertility without any obvious defects in spermatogenesis, sperm count and sperm morphology. Gga1 ablation led to infertility in male mice exposed to BPA, along with a significant reduction in sperm count, sperm motility and the percentage of normal sperm. Histological analysis of the seminiferous epithelium showed that spermatogenesis was severely disorganized, while apoptotic germ cells were significantly increased in the Gga1 null mice exposed to BPA. Our findings suggest that Gga1 protects spermatogenesis against damage induced by environmental pollutants.