Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances

Abstract

Angiotensin (Ang) II is widely known for its role in the control of systemic blood vessels. Moreover, Ang II acts on the vascular control of ovarian function, corpus luteum formation, and luteolysis. Over the past 10 years, our research group has been studying the new concept of the renin-angiotensin system (RAS) as an autocrine/paracrine factor regulating steroidogenesis and promoting different cellular responses in the ovary, beyond vascular function. We have developed and used different in vivo and in vitro experimental models to study the role of RAS in the ovary and a brief overview of our findings is presented here. It is widely accepted that there are marked species differences in RAS function in follicle development. Examples of species-specific functions of the RAS in the ovary include the involvement of Ang II in the regulation of follicle atresia in rats vs the requirement of this peptide for the dominant follicle development and ovulation in rabbits and cattle. More recently, Ang-(1-7), its receptor, and enzymes for its synthesis (ACE2, NEP, and PEP) were identified in bovine follicles, implying that Ang-(1-7) has an ovarian function. Other novel RAS components (e.g. (pro)renin receptor and renin-binding protein) recently identified in the bovine ovary show that ovarian RAS is poorly understood and more complex than previously thought. In the present review, we have highlighted the progress toward understanding the paracrine and autocrine control of ovarian antral follicle development and ovulation by ovarian tissue RAS, focusing on in vivo studies using cattle as a model.

Steroidogenic enzymes mRNA expression profile and steroids production in bovine theca cells cultured in vitro and stimulated with angiotensin II

“…Nevertheless, previous studies in rabbit have demonstrated that Ang II can stimulate testosterone production in theca cells cultured in vitro and treated with hCG (FERAL et al, 1995). These differences are likely due to a specie-specific factors since the RAS system is not uniform in mammals (GONÇALVES et al, 2012). In bovine, there was no effect of Ang II alone or in association with LH on androstenedione or testosterone synthesis in theca cells, neither on progesterone production induced by LH in granulosa cells (PORTELA et al, 2011).…”

Failure of fertility therapy and subsequent adverse cardiovascular events

“…8,9,39 One potential mechanism is direct activation of the renin-angiotensin system with ovarian hyperstimulation, [13][14][15] which influences systemic vascular permeability, sodium balance and blood pressure. 16 Fluid shifts may result in depletion of intravascular volume and interstitial edema that mediates ischemic stroke, heart failure and venothromboembolic risks during pregnancy and potentially thereafter.…”

“…In addition, fertility therapy may lead to adverse cardiovascular events by inducing background thrombosis, activating the renin-angiotensin system or inducing vascular injury from ovarian hyperstimulation. [8][9][10][11][12][13][14][15][16] The last mechanism may be further exacerbated in patients who undergo multiple cycles of fertility therapy or experience pregnancy miscarriages. [17][18][19][20][21] An association between fertility therapy failure and longterm cardiovascular risk could provide insight into nontraditional risk factors potentially contributing to the stagnation in the reduction of cardiovascular mortality observed among young women.…”

Bloqueio do receptor AT1 da Angiotensina II reduz o número de folículos antrais em ratas com obesidade induzida por dieta de cafeteria

“…Receptores AT 1 e AT 2 foram detectados em células da granulosa de folículos primordial, primário e secundários 17 . A Angiotensina II e seus receptores AT 1 e AT 2 parecem exercer efeitos reguladores no ovário em relação à maturação do núcleo do oócito e à ovulação em mulheres 18 . Além disso, folículos com elevada atividade SRA local foram associados com melhor qualidade do ovócito e aumento nas concentrações de fatores de crescimento vascular endotelial durante os procedimentos de fertilização in vitro 19 .…”