Involvement of ACE2/Ang-(1-7)/MAS1 Axis in the Regulation of Ovarian Function in Mammals
Open accessAbstract
In addition to the classic, endocrine renin-angiotensin system, local renin-angiotensin system (RAS) has been documented in many tissues and organs, including the ovaries. The localization and functional activity of the two opposing axes of the system, viz. ACE1/Ang II/AT1 and ACE2/Ang-(1-7)/MAS1, differs between animal species and varied according to the stage of follicle development. It appears that the angiotensin peptides and their receptors participate in reproductive processes such as folliculogenesis, steroidogenesis, oocyte maturation, and ovulation. In addition, changes in the constituent compounds of local RAS may contribute to pathological conditions, such as polycystic ovary syndrome, ovarian hyperstimulation syndrome, and ovarian cancer. This review article examines the expression, localization, metabolism, and activity of individual elements of the ACE2/Ang-(1-7)/MAS1 axis in the ovaries of various animal species. The manuscript also presents the relationship between the secretion of gonadotropins and sex hormones and expression of Ang-(1-7) and MAS1 receptors. It also summarizes current knowledge regarding the positive and negative impact of ACE2/Ang-(1-7)/MAS1 axis on ovarian function.
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In the human ovary, local RAS is involved in supporting oogenesis, regulating ovulation function, synthesizing steroid hormones, and mediating gonadotropin function.
“In the human ovary, local RAS is involved in many important physiological processes such as supporting oogenesis, regulating ovulation function, synthesizing steroid hormones, and mediating gonadotropin function [7, 23–25].”
From Transplantation of human umbilical cord-derived mesenchymal stem cells improves age-related ovarian functional decline via regulating the local renin–angiotensin system on inflammation and oxidative stress (2024) · cites this paper as [24]
The Conclusions (section 7; page unavailable) say ovarian RAS appears to mediate gonadotropin function and is involved in steroidogenesis, but describe its involvement in ovulation as possible. The human-ovary discussion (section 5.5; page unavailable) reports a correlation between follicular-fluid Ang-(1-7) and mature oocytes, not that local RAS supports oogenesis or regulates ovulation in humans. The sentence presents these qualified findings, some drawn across mammalian species, as established human-ovary functions. (LLM, conf=0.87)
Experimental — accuracy not yet measuredThe Ang(1-7) axis exists in the human ovary.
“Since it was first proved that the Ang(1–7) axis exists in the human ovary in 2011 [24]”
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The role of enalapril in the prevention of ovarian hyperstimulation syndrome: a rabbit model
Gul, T. G. (2001) · Human Reproduction · doi:10.1093/humrep/16.11.2253 · Cited by 8 · see citing works
Angiotensin II receptor type 1 on granulosa and thecal cells of rabbit preovulatory follicles
Féral, C., Benhaïm, A., & Leymarie, P. (1996) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/s0005-2736(96)00134-4 · Cited by 7 · see citing works
The effect of angiotensin-converting enzyme inhibition throughout a superovulation protocol in ewes
Pereira, A. M., Júnior, A. D. S., Machado, F. B., Gonçalves, G. K. N., Feitosa, L. C. S., dos Reis, A. M., Santos, R. A. S., Sampaio, K. H., & Costa, A. P. R. (2015) · Research in Veterinary Science · doi:10.1016/j.rvsc.2015.10.013 · Cited by 6 · see citing works
Renin Angiotensin System Components and Cancer: Reports of Association
Wolgien, M. D. C. G. M., Corrêa, S. A. A., Breuel, P. A. F., Nazário, A. C. P., & Facina, G. (2016) · Journal of Biosciences and Medicines · doi:10.4236/jbm.2016.45007 · Cited by 6 · see citing works
Endoplasmic Reticulum Stress during Mammalian Follicular Atresia
Torres‐Ramírez, N., Ortiz-Hernández, R., Escobar-Sánchez, M. L., Echeverría, O. M., & Vázquez‐Nin, G. H. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.82687 · Cited by 3 · see citing works
Flagged first, then by citations
1 of the 98 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
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Cited by
Sorted by citations
Targeting purine metabolism in ovarian cancer
Liu, J., Hong, S., Jiang, Y., Zhang, X., Wang, Y., Wang, H., Peng, J., & Hong, L. (2022) · Journal of Ovarian Research · doi:10.1186/s13048-022-01022-z · Cited by 88 · see citing works
Opportunities, Challenges and Pitfalls of Using Cannabidiol as an Adjuvant Drug in COVID-19
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Mild COVID-19 infection does not alter the ovarian reserve in women treated with ART
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Physiological and pathological roles of Ang II and Ang- (1-7) in the female reproductive system
Liu, Y., Hao, H., Lan, T., Jia, R., Cao, M., Zhou, L., Zhao, Z., & Pan, W. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1080285 · Cited by 20 · see citing works
Effects of COVID-19 Infection and Vaccination on the Female Reproductive System: A Narrative Review
Pourmasumi, S., Kounis, N. G., Naderi, M., Hosseinisadat, R., Khoradmehr, A., Fagheirelahee, N., Kouni, S. N., GREGORIO, C. D., Dousdampanis, P., Mplani, V., et al. (2023) · Balkan Medical Journal · doi:10.4274/balkanmedj.galenos.2023.2023-3-4 · Cited by 19 · see citing works
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Non-Hormonal Strategies in Endometriosis: Targets with Future Clinical Potential
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“Since it was first proved that the Ang(1–7) axis exists in the human ovary in 2011 [24], the most valuable research result is the discovery that Ang(1–7) is positively correlated with oocyte maturation rate [64].”
BackgroundInteraction of SARS-CoV-2 With RAS / ACE2 in the Female Reproductive System
Zangeneh, F. Z. (2022) · Journal of Family & Reproductive Health · doi:10.18502/jfrh.v16i1.8588 · Cited by 10 · see citing works
Effect of prior female SARS-CoV-2 infection on IVF outcomes: a prospective cohort study
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Chen, Q., Liu, R., Wei, C., Wang, X., Wu, X., Fan, R., Yu, X., Li, Z., Mao, R., Hu, J., et al. (2023) · Nutrients · doi:10.3390/nu15245130 · Cited by 9 · see citing works
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Chaudhari, S., Pereira, S. D., Asare-Werehene, M., Naha, R., Kabekkodu, S. P., Tsang, B. K., & Satyamoorthy, K. (2021) · Journal of Ovarian Research · doi:10.1186/s13048-021-00787-z · Cited by 8 · see citing works
Ma, Y., Zhang, Y., Li, S., Yang, H., Li, H., Cao, Z., Xu, F., Sun, L., & Wang, Y. (2021) · Drugs & Aging · doi:10.1007/s40266-021-00886-y · Cited by 8 · see citing works
Braga, D. P. A. F., Setti, A. S., Iaconelli, A., & Borges, E. (2022) · Molecular Reproduction and Development · doi:10.1002/mrd.23658 · Cited by 7 · see citing works
Renin–angiotensin system: a novel target for brain health
Xu, T., Fu, K., Ma, C., Yao, D., & Becker, B. (2025) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2025.10.001 · Cited by 6 · see citing works
Physiological implications of COVID-19 in reproduction: angiotensin-converting enzyme 2 a key player
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Can Coronavirus Disease 2019 Effect on Human Reproduction?
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- Authors
- Domińska, K.
- Affiliations
- Medical University of Lodz (PL)
- Corresponding author
- Domińska, Kamila
- ORCID
- Domińska, Kamila
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-06-27
- Volume
- 21
- Issue
- 13
- Pages
- 4572
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7369927
- OpenAlex
- W3037060068
- Cited by
- 38
- References
- 98
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 3 · 2022: 8 · 2021: 8
- FWCI
- 0.80
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Medical University of Lodz (503/0-078-04/503-01-001)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Keywords
- ACE2, angiotensin-(1-7), local renin-angiotensin system, ovarian function, folliculogenesis, steroidogenesis, oocyte maturation, ovulation, polycystic ovary syndrome, ovarian hyperstimulation syndrome, ovarian cancer, gonadotropins, sex hormones, angiotensin peptides
- MeSH terms
- Angiotensin-Converting Enzyme 2, Proto-Oncogene Mas, Angiotensin I, Animals, Female, Humans, Ovary, Peptide Fragments, Proto-Oncogene Proteins, Receptors, G-Protein-Coupled
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