Knockdown of lncRNA Meg3 delays the onset of puberty in female rats

Abstract

This study investigated how lncRNA Meg3 affects the onset of puberty in female rats. We determined Meg3 expression in the hypothalamus-pituitary-ovary axis of female rats at the infancy, prepubertal, pubertal, and adult life stages, using quantitative reverse transcription polymerase chain reaction (qRT-PCR). We also assessed the effects of Meg3 knockdown on the expression levels of puberty-related genes and Wnt/β-catenin proteins in the hypothalamus, time of puberty onset, levels of reproductive genes and hormones, and ovarian morphology in female rats. Meg3 expression in the ovary varied significantly between prepuberty and puberty (P < 0.01). Meg3 knockdown decreased the expression of Gnrh, and Kiss1 mRNA (P < 0.05) and increased the expression of Wnt (P < 0.01) and β-catenin proteins (P < 0.05) in the hypothalamic cells. Onset of puberty in Meg3 knockdown rats was delayed compared to the control group (P < 0.05). Meg3 knockdown decreased Gnrh mRNA levels (P < 0.05) and increased Rfrp-3 mRNA levels (P < 0.05) in the hypothalamus. The serum concentrations of progesterone (P₄) and estradiol (E₂) of Meg3 knockdown rats were lower than those in the control animals (P < 0.05). Higher longitudinal diameter and ovary weight were found in Meg3 knockdown rats (P < 0.05). These findings suggest that Meg3 regulates the expression of Gnrh, Kiss-1 mRNA and Wnt/β-catenin proteins in the hypothalamic cells, and Gnrh, Rfrp-3 mRNA of the hypothalamus and the serum concentration of P₄ and E₂, and its knockdown delays the onset of puberty in female rats.

Keywords: Hypothalamic–pituitary–gonadal axis; Lentiviral RNAi; Puberty; lncRNA Meg3.