Startseite Gonadotrophins modulate cell death-related genes expression in human endometrium
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Gonadotrophins modulate cell death-related genes expression in human endometrium

  • Sandro Sacchi , Paola Sena , Chiara Addabbo , Erika Cuttone und Antonio La Marca EMAIL logo
Veröffentlicht/Copyright: 17. April 2020
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Abstract

Background

Gonadotrophins exert their functions by binding follicle-stimulating hormone receptor (FSHR) or luteinizing hormone and human chorionic gonadotropin receptor (LHCGR) present on endometrium. Within ovaries, FSH induces autophagy and apoptosis of granulosa cells leading to atresia of non-growing follicles, whereas hCG and LH have anti-apoptotic functions. Endometrial cells express functioning gonadotrophin receptors. The objective of this study was to analyze the effect of gonadotrophins on physiology and endometrial cells survival.

Materials and methods

Collected endometria were incubated for 48 or 72 h with 100 ng/mL of recombinant human FSH (rhFSH), recombinant human LH (rhLH) or highly purified hCG (HPhCG) alone or combined. Controls omitted gonadotrophins. The effect of gonadotrophins on cytochrome P450 family 11 subfamily A polypeptide 1 (CYP11A1), hypoxia inducible factor 1α (HIF1A), and cell-death-related genes expression was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Immunohistochemistry for microtubule-associated proteins 1A/1B light chain 3B (MAP1LC3B) and apoptotic protease activating factor 1 (APAF-1) was performed.

Results

Gonadotrophins are able to modulate the endometrial cells survival. FSH induced autophagy and apoptosis by increasing the relative expression of MAP1LC3B and FAS receptor. In FSH-treated samples, expression of apoptosis marker APAF-1 was detected and co-localized on autophagic cells. hCG and LH does not modulate the expression of cell-death-related genes while the up-regulation of pro-proliferative epiregulin gene was observed. When combined with FSH, hCG and LH prevent autophagy and apoptosis FSH-induced.

Conclusions

Different gonadotrophins specifically affect endometrial cells viability differently: FSH promotes autophagy and apoptosis while LH and hCG alone or combined with rhFSH does not.

Acknowledgment

We are deeply grateful to Professor Franchini Antonella (Life Science Department of the University of Modena and Reggio Emilia) for her patience, advice and in providing assistance with the samples preparation for immunohistochemistry.

Author statement

  1. Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  2. Conflict of interest: None declared.

  3. Informed consent: All patients were required to give written informed consent to allow recording and using of their laboratory and clinical data related to medical history for clinical research purpose.

  4. Ethical approval: Institutional review board approval for this study was obtained.

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Supplementary Material

The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/hmbci-2019-0074).


Received: 2019-12-09
Accepted: 2020-02-18
Published Online: 2020-04-17

© 2020 Walter de Gruyter GmbH, Berlin/Boston

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