Association of the Renin-Angiotensin System Components in Human Follicular Fluid with Age, Ovarian Function and IVF Outcome: A Cross-Sectional Study

Abstract

Abstract Background Previous studies have found that there is the local renin-angiotensin system (RAS) in human ovary, and it independently plays a regulatory role in ovarian function. Age-related reproductive aging is an inevitable process. To explore the relationship between RAS components in human follicular fluid (hFF) and age, ovarian function, so as to help clinical evaluation of oocyte quality and prediction of in vitro fertilization (IVF) outcome. Methods hFF of 139 women who received IVF simply because of their husband's factors from January 2021 to February 2022. The levels of RAS components in hFF were measured, including Renin, ACE, ACE2, AngⅡ and Ang(1–7). The correlation between age and RAS in hFF was analyzed by simple linear regression, and multivariate linear regression was used to further analyze the correlation between the RAS and IVF outcome. Results A total of 139 samples of analysable hFF were obtained in this study. It was found that there was a linear negative correlation between age and renin, ACE, AngⅡ, ACE/ACE2, AngⅡ/Ang(1–7) (Pearson's r < 0, P < 0.05), while the linear relationship with ACE2 and Ang (1–7) was not significant (P > 0.05). It was found that bFSH and bLH were correlated with age, ACE-AngⅡ-AT1/2R axis, ACE2-Ang(1–7)-MAS axis (P < 0.05), AFC was correlated with age, ACE2-Ang(1–7)-MAS axis (P < 0.05), and bAMH was only correlated with age (P < 0.01). There was no correlation between RAS and bE2, bP, bPRL, bT (P > 0.05). It was found that the number of oocyte retrieval and MⅡ maturation rate were correlated with age, renin, ACE-AngⅡ-AT1/2R axis and ACE2-Ang(1–7)-MAS axis (P < 0.05), and the rate of 2PN embryos, transplantable embryos, high-quality embryos were only correlated with age (P < 0.01). Conclusions ①The influence of age on ACE-AngⅡ-AT1/2R axis was more significant than that on ACE2-Ang(1–7)-MAS axis in hFF; ②Provides evidence that gonadotropins mediate RAS activation of local ovarian follicles; ③It is still impossible to prove the effect of RAS on steroid hormone production, at least in ovarian follicles RAS cannot affect steroid hormones in the systemic circulation; ④Age and the level of RAS components in hFF have certain clinical value in predicting the number of oocyte retrieval and the rate of MⅡ maturation.