Expression and Distribution Pattern of DNMT1 and MeCP2 and their Relationship with GnRH and Kisspeptin in the Hypothalamus during Puberty Onset in Ewes

Abstract

Background: The puberty onset is directly related to the sexual maturity and reproductive performance of ewes and the economic benefits of sheep raising industry. Previous studies have shown that DNA methylation in hypothalamus plays an important role in puberty onset of female mammals, but the mechanism is still unclear. The present study aims to investigate the expression and distribution of DNA methyltransferase 1 (DNMT1) and Methyl-CpG-binding protein 2 (MeCP2) and their relationship with Gonadotropin-releasing hormone (GnRH) and kisspeptin in the hypothalamus during the onset of puberty in ewes.Methods: We choose three female small-tailed Han sheep at peri-puberty, pre-puberty and puberty respectively. There after, hypothalamus tissue samples from each ewe were harvested for Real-Time quantitative PCR and double-labeling immunofluorescence.Result: The mRNA expression of GnRH and KiSS-1 were increased significantly, while the mRNA expression levels of DNMT1 and MeCP2 decreased during puberty onset in ewes. DNMT1 and MeCP2 were uniformly distributed in preoptic area (POA) and arcuate nucleus (ARC) in the hypothalamus and both exhibits co-expression patterns with GnRH and kisspeptin. The rate of co-expressing positive cells increased in ARC, while it decreased in POA during puberty onset in ewes. The results indicate that DNMT1 and MeCP2 might be involved in puberty onset through co-expression with GnRH and kisspeptin in the hypothalamus of ewes. Our findings not only provide a reference for the comprehensive understanding of the mechanism for mammalian puberty onset, but also lay a foundation for improving reproductive capacity of ewes.