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.

Effect of progesterone administration on tissue mast cell population and histamine content in mice uterus after induction of ovulation

“…Then pseudo pregnancy was performed and after 3.5 days the animals were slaughtered for the study. Concerning the progesterone group (n=5), the process in the induction group was performed followed by daily administration of 1 mg subcutaneous (SC) progesterone for up to 3.5 days ( Narimani et al ., 2020 ). Ethical guidelines for working with laboratory animals were followed and the protocol of this study was approved in the ethics committee of Lorestan University of Medical Sciences under registration number IR.LUMS.REC.1399.300.…”

Progesterone signaling in the regulation of luteal steroidogenesis

“…Progesterone seems to support its own synthesis by inducing luteal vascularization ( Curry and Nothnick, 1996 ; Pall et al , 2000 ; Stouffer, 2003 ; Peluso et al , 2018 ). Progesterone is known to increase the expression of the vascular endothelial growth factor (VEGF) gene in ovarian tissue in mice ( Narimani et al , 2020 ), granulosa and theca cells in ewes ( Narimani et al , 2020 ), cows ( Shimizu and Miyamoto, 2007 ), and cattle ( Nichols et al , 2019 ). Inhibition of PGRMC1/2 activity is associated with a reduction in the number of vascular endothelial cells within the mouse corpus luteum ( Peluso et al , 2018 ), This effect seems to be independent of VEGF-A but rather related to another novel angiogenesis regulator, lipocalin 2, as its expression in corpus luteum is dependent on the presence of PGRMC1/2.…”

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 ].…”