Ovarian stimulation and exogenous progesterone affect the endometrial miR-16-5p, VEGF protein expression, and angiogenesis

Abstract

Angiogenesis, where vascular endothelial growth factor (VEGF) is critically involved, is an important factor in endometrial receptivity. Angio-miRNAs form a special class of microRNAs (miRNAs) that target angiogenic genes and regulate angiogenesis. Various studies have shown that ovarian stimulation and exogenous progesterone affect endometrial vascular density. The present research aimed to assess the impact of HMG/HCG and progesterone on miR-16-5p, VEGF protein expression, and angiogenesis in the mouse endometrium during the preimplantation period. Forty adult female mice were divided into four groups: 1) control, 2) ovarian stimulation (HMG and 48 h after HCG IP), 3) progesterone (progesterone IP for 3 days), 4) ovarian stimulation + progesterone (HMG and 48 h after HCG IP) + (progesterone IP for 3 days) groups.The mice were sacrificed 96 h following HCG administration. miR-16-5p, VEGF protein expression, and CD31-positive cell (Endothelial cell) density were specified.The results showed that endothelial cell density,VEGF protein, and miR-16-5p expression increased in all treatment groups, with the maximum increase belonging to the ovarian stimulation + progesterone group. This study provides evidence that ovarian stimulation and progesterone administration enhance endometrial angiogenesis through VEGF protein upregulation. Furthermore, except for miR-16-5p, other miRNAs and molecules appear to be involved in angiogenic pathways, thereby requiring further studies.