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Effects of Gonadotropin-Releasing Hormone (GnRH) and Its Analogues on the Physiological Behaviors and Hormone Content of Tetrahymena pyriformis
Open AccessArticle

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

1
UOS Physiopathology of Human Reproduction, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
2
Breast Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
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Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genoa, 16132 Genoa, Italy
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Department of Internal Medicine, University of Genoa, 16132 Genoa, Italy
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U.O.C. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, 16132 Genoa, Italy
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Infrastruttura Ricerca e Statistica, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(23), 6045; https://doi.org/10.3390/ijms20236045
Received: 30 October 2019 / Revised: 22 November 2019 / Accepted: 25 November 2019 / Published: 30 November 2019
(This article belongs to the Special Issue The Role of Gonadotropin-Releasing Hormone Receptor in Human Diseases)
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. View Full-Text
Keywords: cyclophosphamide; GnRH agonist; apoptosis; oocytes; human cumulus cell-oocyte complexes cyclophosphamide; GnRH agonist; apoptosis; oocytes; human cumulus cell-oocyte complexes
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Scaruffi, P.; Stigliani, S.; Cardinali, B.; Massarotti, C.; Lambertini, M.; Sozzi, F.; Dellepiane, C.; Merlo, D.F.; Anserini, P.; Del Mastro, L. Gonadotropin Releasing Hormone Agonists Have an Anti-apoptotic Effect on Cumulus Cells. Int. J. Mol. Sci. 2019, 20, 6045.

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