Pre-implantation effects of progesterone administration on ovarian angiogenesis after ovarian stimulation: a histological, hormonal, and molecular analysis

Abstract

Objective: Progesterone (P4) is known to directly affect ovarian tissue angiogenesis. The present study was designed to show how P4 affects ovarian angiogenesis in hormonal, histological, and molecular levels. Methods: Fifteen adult female NMRI mice were divided into three groups: Control Group; Case Group I (ovarian stimulation alone); and Case Group II (ovarian stimulation followed by P4 administration). Blood and ovarian tissue samples were assessed for hormonal, histological, and molecular alterations. Gene expression for ovarian vascular endothelium growth factor (VEGF) and hypoxia-inducible factor-1 alpha (HIF-1α) was analyzed using real-time PCR. Results: Ovarian hormone levels were increased in the case groups compared with the control group ( p <0.05). Quantitative corpus luteum parameters were increased in the case groups compared with the control group ( p <0.05). Quantitative ovarian vascular parameters were significantly different in the case groups compared with the control group. Gene expression analyses shows that the mice in Case Group I had higher levels of ovarian VEGF expression than the mice in the control group ( p <0.05). No significant difference in gene expression was observed for HIF-1ɑ. Conclusion: Treatment with P4 after ovarian stimulation enhanced ovarian angiogenesis by increasing hormone levels and causing significant structural changes.

Solving the Puzzle: What Is the Role of Progestogens in Neovascularization?

“…These observations support the vital role of VEGF in progestogen-mediated neovascularization. In addition to in the endometrium, progestogens promote VEGF expression in skin flaps [ 32 ], ovarian tissue [ 33 , 34 ], bovine granulosa cells [ 35 , 36 ], embryonic lung cells [ 37 ], granulomas [ 38 ] and tumor tissues [ 39 , 40 , 41 , 42 ]. However, Keck et al reported an opposite result, founding that P4 has no impact on the proliferation rate of human umbilical vein endothelial cells (HUVECs), a macrovascular cell model used for endothelial studies in vitro [ 43 ].…”