GRPR down-regulation inhibits spermatogenesis through Ca mediated by PLCβ/IP3R signaling pathway in long-term formaldehyde-exposed rats.

Formaldehyde (FA), which is known as an air pollutant, has been proven to induce male infertility. However, the underlying mechanism of FA-induced male infertility remains elusive. In this study, 24 male SD rats were exposed to different levels of FA (0, 0.5, 2.46, and 5 mg/m) for eight consecutive weeks. Through HE staining and sperm smear, we observed that FA exposure resulted in spermatogenic injury and the sperm quality decreased in rats. The qRT-PCR and Western blot analysis further revealed that GRPR was down-regulated in testicular tissues of FA-exposed rats as well as primary spermatogenic cells. Meanwhile, ZDOCK uncovered an interaction between GRPR and PLCβ. In addition, the CCK8, Fluo 3-AM and Flow cytometry results showed that FA exposure suppressed the expression of GRPR, PLCβ and IP3R, consequently reducing the Ca concentration in spermatogenic cells, inducing apoptosis and inhibiting proliferation of spermatogenic cells. Moreover, rescue experiments confirmed that promoting GRPR could improve intracellular Ca concentration by upregulating PLCβ and IP3R, partially reducing the apoptosis and promoting the proliferation of FA-treated spermatogenic cells. These findings revealed that GRPR participates in spermatogenesis through Ca mediated by the PLCβ/IP3R signaling pathway in FA-exposed rats.