Manganese exposure caused reproductive toxicity of male mice involving activation of GnRH secretion in the hypothalamus by prostaglandin E2 receptors EP1 and EP2

Exposure to manganese (Mn) can cause male reproductive damage and lead to abnormal secretion of sex hormones. Gonadotropin-releasing hormone (GnRH) plays an important role in the neuromodulation of vertebrate reproduction. Astrocytes can indirectly regulate the secretion of GnRH by binding paracrine prostaglandin E2 (PGE2) specifically to the EP1 and EP2 receptors on GnRH neurons. Prior studies assessed the abnormal secretion of GnRH caused by Mn exposure, but the specific mechanism has not been reported in detail. This study investigated the effects of Mn exposure on the reproductive system of male mice to clarify the role of PGE2 in the abnormal secretion of GnRH in the hypothalamus caused by exposure to Mn. Our data demonstrate that antagonizing the EP1 and EP2 receptors of PGE2 can restore abnormal levels of GnRH caused by Mn exposure. Mn exposure causes reduced sperm count and sperm shape deformities. These findings suggest that EP1 and EP2, the receptors of PGE2, may be the key to abnormal GnRH secretion caused by Mn exposure. Antagonizing the PGE2 receptors may reduce reproductive damage caused by Mn exposure.