The effect of manganese exposure on GnRH secretion via Nrf2/mGluR5/COX-2/PGE2/signaling pathway:

There are limited studies focused on the precise mechanism of gonadotropin-releasing hormone (GnRH) secretion dysfunction after overexposure to manganese (Mn). The objective of the present study was to explore the mechanism of Mn disruption of GnRH synthesis via nuclear factor erythroid-2-related factor-2 (Nrf2)/metabotropic glutamate receptor-5 (mGluR5)/cyclooxygenase-2 (COX-2)/prostaglandin E2 (PGE2) signaling pathway in vitro and in vivo. Primary astrocytes were cultured and treated with different doses of Mn, tert-butylhydroquinonet (tBHQ; Nrf2 agonists), 3-[(2-methyl-4-thaizolyl) ethynyl] pyridine (MTEP; mGluR5 inhibitor), and celecoxib (COX-2 inhibitor) to measure the levels of COX-2, mGluR5, Nrf2, and Nrf2 target genes. Mice were randomly divided into 11 groups, of which included the control group, 12.5-, 25-, and 50-mg/kg MnCl2 group, dimethyl sulfoxide (DMSO) group, tBHQ control group, tBHQ pretreatment group, MTEP control group, MTEP pretreatment group, celecoxib control group, and celecoxib pre...