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Impact of human ovarian tissue manipulation on follicles: evidence of a potential first wave of follicle activation during fertility preservation procedures

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Abstract

Purpose

The aim of this study was to investigate the impact of processing human ovarian tissue on follicle activation dynamics.

Methods

Fresh ovarian tissue was retrieved from 9 women undergoing laparoscopic surgery for benign conditions. Biopsies from each patient were divided into 3 fragments, the first of which was immediately fixed in the operating room (T0) and the second and third just after processing at 25 (T25) and (T90) 90 min. To evaluate follicle activation, markers of the PI3K and Hippo signaling pathways were immunolabeled at each time point, targeting phospho-Akt (p-Akt) by immunohistochemistry and yes-associated protein (YAP) cellular localization in the granulosa cell layer by immunofluorescence.

Results

Four hundred forty primordial follicles were evaluated for p-Akt and 420 for YAP. Significantly stronger p-Akt expression was observed at T25 (23.01 ± 13.45%; p=0.04) and T90 (38.99 ± 25.21%; p<0.001) than at T0 (2.72 ± 3.35%). A significant nucleus-to-cytoplasm shift in YAP was detected at T25 (1.21 ± 0.25; p=0.015 compared to T0 (0.95 ± 0.09), while T90 (1.10 ± 0.16) values were similar to T25.

Conclusion

Our data prove that ovarian tissue manipulation significantly impacts follicle dynamics by stimulating the PI3K and Hippo signaling pathways involved in primordial follicle activation. Further experimental evidence must nevertheless be gathered to understand and gain control of follicle activation mechanisms in non-physiological conditions (like ovarian tissue manipulation), in order to optimize fertility preservation and restoration strategies.

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Acknowledgements

The authors thank Mira Hryniuk, B.A., for reviewing the English language of the manuscript, Maria Dolores Gonzalez and Olivier Van Kerk for their technical assistance, Francisco Vitale for his help with the statistical analysis, and the IREC-2IP imaging platform for their contribution to image processing.

Funding

This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (CDR J.0063.20, FNRS-PDR T.0064.22, grant 5/4/150/5 awarded to MM. Dolmans and Télévie grant 7.6511.20F awarded to C. Hossay).

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Authors and Affiliations

  1. Gynecology Research Unit, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Avenue Mounier 52, bte B1.52.02, 1200, Brussels, Belgium

    Marta Barretta, Luciana Cacciottola, Camille Hossay & Marie-Madeleine Dolmans

  2. Department of Biomedical Science for Health, University of Milan, Milan, Italy

    Marta Barretta

  3. Université Catholique de Louvain, Brussels, Belgium

    Jacques Donnez

  4. Société de Recherche pour l’Infertilité, Brussels, Belgium

    Jacques Donnez

  5. Gynecology Department, Cliniques Universitaires Saint-Luc, Avenue Mounier 52, bte B1.52.02, 1200, Brussels, Belgium

    Marie-Madeleine Dolmans

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  1. Marta Barretta
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  4. Jacques Donnez
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Correspondence to Marie-Madeleine Dolmans.

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Barretta, M., Cacciottola, L., Hossay, C. et al. Impact of human ovarian tissue manipulation on follicles: evidence of a potential first wave of follicle activation during fertility preservation procedures. J Assist Reprod Genet 40, 2769–2776 (2023). https://doi.org/10.1007/s10815-023-02930-9

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