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FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants

Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pre...

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Autores principales: Eozenou, Caroline, Lesage-Padilla, Audrey, Mauffré, Vincent, Healey, Gareth D., Camous, Sylvaine, Bolifraud, Philippe, Giraud-Delville, Corinne, Vaiman, Daniel, Shimizu, Takashi, Miyamoto, Akio, Sheldon, Iain Martin, Constant, Fabienne, Pannetier, Maëlle, Sandra, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073057/
https://www.ncbi.nlm.nih.gov/pubmed/32098259
http://dx.doi.org/10.3390/ijms21041478
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author Eozenou, Caroline
Lesage-Padilla, Audrey
Mauffré, Vincent
Healey, Gareth D.
Camous, Sylvaine
Bolifraud, Philippe
Giraud-Delville, Corinne
Vaiman, Daniel
Shimizu, Takashi
Miyamoto, Akio
Sheldon, Iain Martin
Constant, Fabienne
Pannetier, Maëlle
Sandra, Olivier
author_facet Eozenou, Caroline
Lesage-Padilla, Audrey
Mauffré, Vincent
Healey, Gareth D.
Camous, Sylvaine
Bolifraud, Philippe
Giraud-Delville, Corinne
Vaiman, Daniel
Shimizu, Takashi
Miyamoto, Akio
Sheldon, Iain Martin
Constant, Fabienne
Pannetier, Maëlle
Sandra, Olivier
author_sort Eozenou, Caroline
collection PubMed
description Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pregnancy signal in cattle, interferon-Tau, does not regulate FOXL2 expression. Therefore, in the present study, we examined whether the ovarian steroid hormones that orchestrate implantation regulate FOXL2 gene expression in ruminants. In sheep, we confirmed that FOXL2 mRNA and protein was expressed in the endometrium across the oestrous cycle (day 4 to day 15 post-oestrus). Similar to the bovine endometrium, ovine FOXL2 endometrial expression was low during the luteal phase of the oestrous cycle (4 to 12 days post-oestrus) and at implantation (15 days post-oestrus) while mRNA and protein expression significantly increased during the luteolytic phase (day 15 post-oestrus in cycle). In pregnant ewes, inhibition of progesterone production by trilostane during the day 5 to 16 period prevented the rise in progesterone concentrations and led to a significant increase of FOXL2 expression in caruncles compared with the control group (1.4-fold, p < 0.05). Ovariectomized ewes or cows that were supplemented with exogenous progesterone for 12 days or 6 days, respectively, had lower endometrial FOXL2 expression compared with control ovariectomized females (sheep, mRNA, 1.8-fold; protein, 2.4-fold; cattle; mRNA, 2.2-fold; p < 0.05). Exogenous oestradiol treatments for 12 days in sheep or 2 days in cattle did not affect FOXL2 endometrial expression compared with control ovariectomized females, except at the protein level in both endometrial areas in the sheep. Moreover, treating bovine endometrial explants with exogenous progesterone for 48h reduced FOXL2 expression. Using in vitro assays with COS7 cells we also demonstrated that progesterone regulates the FOXL2 promoter activity through the progesterone receptor. Collectively, our findings imply that endometrial FOXL2 is, as a direct target of progesterone, involved in early pregnancy and implantation.
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spelling pubmed-70730572020-03-19 FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants Eozenou, Caroline Lesage-Padilla, Audrey Mauffré, Vincent Healey, Gareth D. Camous, Sylvaine Bolifraud, Philippe Giraud-Delville, Corinne Vaiman, Daniel Shimizu, Takashi Miyamoto, Akio Sheldon, Iain Martin Constant, Fabienne Pannetier, Maëlle Sandra, Olivier Int J Mol Sci Article Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pregnancy signal in cattle, interferon-Tau, does not regulate FOXL2 expression. Therefore, in the present study, we examined whether the ovarian steroid hormones that orchestrate implantation regulate FOXL2 gene expression in ruminants. In sheep, we confirmed that FOXL2 mRNA and protein was expressed in the endometrium across the oestrous cycle (day 4 to day 15 post-oestrus). Similar to the bovine endometrium, ovine FOXL2 endometrial expression was low during the luteal phase of the oestrous cycle (4 to 12 days post-oestrus) and at implantation (15 days post-oestrus) while mRNA and protein expression significantly increased during the luteolytic phase (day 15 post-oestrus in cycle). In pregnant ewes, inhibition of progesterone production by trilostane during the day 5 to 16 period prevented the rise in progesterone concentrations and led to a significant increase of FOXL2 expression in caruncles compared with the control group (1.4-fold, p < 0.05). Ovariectomized ewes or cows that were supplemented with exogenous progesterone for 12 days or 6 days, respectively, had lower endometrial FOXL2 expression compared with control ovariectomized females (sheep, mRNA, 1.8-fold; protein, 2.4-fold; cattle; mRNA, 2.2-fold; p < 0.05). Exogenous oestradiol treatments for 12 days in sheep or 2 days in cattle did not affect FOXL2 endometrial expression compared with control ovariectomized females, except at the protein level in both endometrial areas in the sheep. Moreover, treating bovine endometrial explants with exogenous progesterone for 48h reduced FOXL2 expression. Using in vitro assays with COS7 cells we also demonstrated that progesterone regulates the FOXL2 promoter activity through the progesterone receptor. Collectively, our findings imply that endometrial FOXL2 is, as a direct target of progesterone, involved in early pregnancy and implantation. MDPI 2020-02-21 /pmc/articles/PMC7073057/ /pubmed/32098259 http://dx.doi.org/10.3390/ijms21041478 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Eozenou, Caroline
Lesage-Padilla, Audrey
Mauffré, Vincent
Healey, Gareth D.
Camous, Sylvaine
Bolifraud, Philippe
Giraud-Delville, Corinne
Vaiman, Daniel
Shimizu, Takashi
Miyamoto, Akio
Sheldon, Iain Martin
Constant, Fabienne
Pannetier, Maëlle
Sandra, Olivier
FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title_full FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title_fullStr FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title_full_unstemmed FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title_short FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
title_sort foxl2 is a progesterone target gene in the endometrium of ruminants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7073057/
https://www.ncbi.nlm.nih.gov/pubmed/32098259
http://dx.doi.org/10.3390/ijms21041478
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