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The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes
Alécio Matos Pereira1, Antônio de Souza Júnior1, Fernanda Brandão Machado2
1Universidade Federal do Piauí, Teresina, PI, Brazil.
Abstract:
Many studies identified new components of the renin–angiotensin system (RAS), such as Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), in mammalian ovaries.We previously showed Angiotensin-Converting Enzyme (ACE) inhibition, which increases the level of Ang-(1–7), stimulated ovarian estradiol output in ewe after estrous synchronization. Considering that Ang-(1–7) stimulates ovarian function and elevated estradiol before ovulation is associated with increased chance of achieving pregnancy, the present study investigated whether ACE inhibition throughout a superovulation protocol in ewe might improve ovulation outcome. At first, immunohistochemistry in ovaries of nonpregnant ewes revealed localization of Angiotensin II (Ang II), Ang-(1–7) and ACE2 in theca cells of antral follicles and in corpus luteum. Ang II and Ang-(1–7)were also detected in follicular fluid (FF) by Radioimmunoassay (RIA). Enalapril treatment throughout the superovulation protocol decreased 17β-estradiol (E2) output and raised progesterone:estradiol (P4:E2) ratio without a direct influence on ovulation and quality of embryos.
Insights
Angiotensin-Converting Enzyme (ACE) inhibition in ewes did not improve ovulation outcomes during superovulation. While ACE inhibition altered hormone levels, it did not directly impact embryo quality or ovulation rates.
Area of Science:
- Reproductive biology
- Endocrinology
- Mammalian ovarian function
Background:
- The renin-angiotensin system (RAS) components, including Angiotensin-(1-7) [Ang-(1–7)] and Angiotensin-converting enzyme type 2 (ACE2), are present in mammalian ovaries.
- Previous research indicated that Angiotensin-Converting Enzyme (ACE) inhibition enhances ovarian estradiol output in ewes.
- Elevated estradiol levels before ovulation are linked to improved pregnancy rates.
Purpose of the Study:
- To investigate the effect of ACE inhibition during a superovulation protocol on ovulation outcomes in ewes.
- To determine if ACE inhibition influences ovarian hormone production and embryo quality in the context of superovulation.
Main Methods:
- Immunohistochemistry was used to localize Angiotensin II (Ang II), Ang-(1–7), and ACE2 in ovarian tissues (theca cells, corpus luteum).
- Radioimmunoassay (RIA) was employed to quantify Ang II and Ang-(1–7) levels in follicular fluid (FF).
- Ewes underwent a superovulation protocol with Enalapril treatment (ACE inhibitor).
Main Results:
- Ang II, Ang-(1–7), and ACE2 were localized in theca cells of antral follicles and corpus luteum.
- Ang II and Ang-(1–7) were detected in follicular fluid.
- Enalapril treatment reduced 17β-estradiol (E2) output and increased the progesterone:estradiol (P4:E2) ratio.
- Ovulation rates and embryo quality were not directly influenced by ACE inhibition.
Conclusions:
- ACE inhibition during superovulation in ewes alters ovarian hormone profiles, specifically decreasing estradiol and increasing the P4:E2 ratio.
- Despite hormonal changes, ACE inhibition does not enhance ovulation rates or embryo quality in this superovulation model.
- The role of the ovarian RAS in superovulation requires further investigation, as ACE inhibition did not yield the anticipated improvements in reproductive outcomes.

