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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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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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. |
format | Online Article Text |
id | pubmed-7073057 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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