Metabolism of renin-angiotensin and enkephalin in human follicular fluid: An experimental study

Victoria Rodríguez Gallego M, María Victoria Rodríguez Gallego, Maria Victoria Rodríguez Gallego, María Victoria Aparicio Prieto, Maria Victoria Aparicio Prieto, A. Leza, Andrea Leza García, Juana Hernández, Juana Hernández Hernández, Hernández Hernández J, Antonio Arizaleta Uralde J, Jose Antonio Arizaleta Uralde, Luı́s Casis, Casis Sáenz L, Luis Casis Sáenz
International journal of reproductive biomedicine · 2022 · vol. 20(10) , pp. 851–860 · doi:10.18502/ijrm.v20i10.12269 · PMID:36381359 · PMC9644645 · W4308318192
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⚙ AI-generated summary by claude@2026-06, 2026-06-12 ⓘ

This study analyzed peptide metabolism in human follicular fluid from women undergoing IVF, finding alterations in enkephalin and angiotensin systems in pathological samples compared to controls.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-12 · read from full text ⓘ

This experimental study measured enzymatic activities involved in local follicular-fluid metabolism of enkephalin-related peptidases (aminopeptidase-N/APN, puromycin-sensitive aminopeptidase/PSA, and neutral endopeptidase/NEP) and renin-angiotensin system peptidases (prolyl endopeptidase/PEP, APN, aspartate-aminopeptidase/Asp-AP, and basic aminopeptidase/APB) in follicular fluid from 30 women undergoing IVF, with 3 independently aspirated follicle samples per person (82 non-hemolyzed samples analyzed). Key findings were that within-individual sample variability was not observed and the presence/absence of an oocyte did not change peptidase activities, while PSA activity was significantly increased in endometriosis and age >39 groups and APB activity was significantly reduced in the endometriosis group; the paper also reports lowest Asp-AP activity in endometriosis with highest levels in unexplained infertility. A major limitation is the small, preliminary sample size with group sizes that differ by inclusion criteria and broad age ranges, along with ex vivo activity assays rather than direct substrate/peptide concentration measurements. Relevance to endometriosis: the study includes an endometriosis group and reports specific differences in PSA and APB (and Asp-AP) enzymatic activity in follicular fluid from women with endometriosis, linking peptidase-mediated peptid metabolism to endometriosis in the context of IVF-derived samples.

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Abstract

BACKGROUND: The relationship between the biochemical characteristics of follicular fluid (FF), oocyte quality and embryonic development has not yet been elucidated. We compared samples of FF with a normal metabolic profile against samples with metabolic abnormalities to identify potential predictive biomarkers of reproductive success. OBJECTIVE: To analyze peptide activity in the FF of women undergoing in vitro fertilization using 3 samples of FF per individual. MATERIALS AND METHODS: FF samples were obtained by ovum pick-up. Pathological samples were defined as samples of FF obtained from women with a gynecological condition or with infertility. A total of 30 women participated in this study. 3 samples of FF were obtained per individual (90 samples), but 8 samples were excluded because they were hemolyzed. The samples (n = 82 FF) included controls (n = 36, donors without fertility problems), women with endometriosis (n = 15), unexplained infertility (n = 19), and aged > 39 (n = 12). We assessed local encephalinergics: aminopeptidase-N (puromycin sensitive aminopeptidase and neutral endopeptidase; and components of the angiotensin system of the reproductive tract: prolyl-endopeptidase, APN, aspartate-aminopeptidase, and basic-aminopeptidase. RESULTS: No differences were observed in peptide metabolism based on the presence or absence of oocytes in the FF. Women with endometriosis and aged > 39 yr showed alterations in puromycin sensitive aminopeptidase (p = 0.01), aminopeptidase-B (p = 0.01), aspartate-aminopeptidase (p < 0.001) and neutral endopeptidase (p < 0.001). CONCLUSION: This study reveals alterations in the metabolism of enkephalin and angiotensin in pathological FF, which points to these components as potential diagnostic biomarkers.
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The results obtained in this study suggest that an adverse follicular environment shows alterations in the metabolism of enkephalins and angiotensins. Therefore, some of these peptides can be used as diagnostic biomarkers. However, due to the limitations of the study (i.e., the limited number of samples), further studies are needed to verify the role of these peptides in FF stability and to validate the value of FF components as predictive biomarkers of reproductive success.

Coi Statement

The authors declare that there is no conflict of interest.

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endometriosisinfertility

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