Gonadotropin Releasing Hormone Agonists Have an Anti-apoptotic Effect on Cumulus Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2019 Dec 6

PMID 31801245

Citations 10

Authors

Paola Scaruffi

Sara Stigliani

Barbara Cardinali

Claudia Massarotti

Matteo Lambertini

Fausta Sozzi

Chiara Dellepiane

Domenico Franco Merlo

Paola Anserini

Lucia Del Mastro

Affiliations

Soon will be listed here.

Abstract

Background: Ovaries are sensitive to chemotherapy, which may lead to early depletion of primordial follicle reserve. One strategy for gonadal function preservation is temporary ovarian suppression with Gonadotropin Releasing Hormone agonists (GnRHa) during chemotherapy. To date, GnRHa protective mechanism of action remains not fully elucidated.

Methods: We collected 260 immature cumulus cell-oocyte complexes (COC) from 111 women < 38 years old, with a normal ovarian reserve. The COC were randomly assigned to the following groups: a) control; culture with the addition of b) GnRHa; c) cyclophosphamide; d) cyclophosphamide plus GnRHa. After in vitro treatments, RNA and proteins were extracted from oocytes and cumulus cells (CC), separately. Potential effects of drugs were evaluated on GnRH receptors, apoptosis pathways, ceramide pathway, and glutathione synthesis by quantitative PCR and, whenever possible, by Western blot.

Results: Cyclophosphamide triggered activation of the extrinsic pathway of apoptosis mediated by BAX in CC. The co-administration of GnRHa inhibited the apoptosis pathway in CC. According to our model, the GnRHa does not directly act on oocytes, which do not express GnRH receptors. Moreover, glutathione synthesis was decreased after GnRHa treatment both in CC and oocytes.

Conclusion: Our data suggest that the protective mechanisms induced by GnRHa is mediated by an anti-apoptotic effect on CC.

Citing Articles

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Long-acting gonadotropin-releasing hormone agonist trigger in fertility preservation cycles before chemotherapy.

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The effects and mechanism of taxanes on chemotherapy-associated ovarian damage: A review of current evidence.

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Yuan J, Lai Y, Li T Ann Transl Med. 2022; 10(7):409.

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GnRH Analogues as a Co-Treatment to Therapy in Women of Reproductive Age with Cancer and Fertility Preservation.

Valsamakis G, Valtetsiotis K, Charmandari E, Lambrinoudaki I, Vlahos N Int J Mol Sci. 2022; 23(4).

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