FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants

被引:13
|
作者
Eozenou, Caroline [1 ,2 ]
Lesage-Padilla, Audrey [1 ]
Mauffre, Vincent [1 ]
Healey, Gareth D. [3 ]
Camous, Sylvaine [1 ]
Bolifraud, Philippe [1 ]
Giraud-Delville, Corinne [1 ]
Vaiman, Daniel [4 ]
Shimizu, Takashi [5 ]
Miyamoto, Akio [5 ]
Sheldon, Iain Martin [3 ]
Constant, Fabienne [1 ]
Pannetier, Maelle [1 ]
Sandra, Olivier [1 ]
机构
[1] Univ Paris Saclay, BREED, ENVA, INRAE,UVSQ, F-78350 Jouy En Josas, France
[2] Inst Pasteur, Lab Genet Dev Humain, UMR 3738, Biol Dev & Cellules Souches, 25 Rue Docteur Roux, F-75015 Paris, France
[3] Swansea Univ, Med Sch, Singleton Pk, Swansea SA2 8PP, W Glam, Wales
[4] Fac Rene Descartes, Inst Cochin, UMR CNRS 8104, INSERM U1016, 24 Rue Faubourg St Jacques, F-75014 Paris, France
[5] Obihiro Univ Agr & Vet Med, Obihiro, Hokkaido 0808555, Japan
关键词
FOXL2; endometrium; sheep; cattle; progesterone; TRANSCRIPTION FACTOR FOXL2; MENSTRUAL-CYCLE; CONCEPTUS DEVELOPMENT; MATERNAL RECOGNITION; UTERINE RECEPTIVITY; BOVINE ENDOMETRIUM; POTENTIAL TARGETS; EARLY-PREGNANCY; MESSENGER-RNA; ESTROUS-CYCLE;
D O I
10.3390/ijms21041478
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:17
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