Melatonin promotes the proliferation of GC-1 spg cells by inducing metallothionein-2 expression through ERK1/2 signaling pathway activation

Abstract

Synthesized by the pineal gland, melatonin is a neurohormone implicated in diverse physiological functions via several mechanisms. However, the role of melatonin in spermatogenesis and its underlying mechanisms have yet to be completely understood. In the present study, transcriptome sequencing was performed to characterize the mechanism of melatonin-induced GC-1 spg proliferation. Gene ontology (GO) enrichment and pathway analyses were also conducted to identify the signaling pathways and biological processes involved in differential mRNA expression. Results revealed 28 differential genes. Of these genes, 11 were upregulated and 17 were downregulated. Melatonin increased the expression of metallothionein-2 (Mt2), a gene that acts as a protector to sequester nonessential toxic heavy metals. Functional investigations demonstrated that Mt2 overexpression promoted the proliferation of GC-1 spg cells, but Mt2 knockdown significantly suppressed their proliferation and increased their apoptosis. Mechanistic analysis indicated that the extracellular-signal-regulated kinase 1/2 (ERK1/2) pathway participated in melatonin-promoted proliferation of GC-1 spg cells. Therefore, melatonin induces the proliferation of GC-spg 1 cells by stimulating Mt2 expression, and this process is mediated by the ERK1/2 signaling pathway.