Syracuse

Nuclear orphan receptor COUP-TFII in reproduction

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Tsai, Sophia y | Kurihara, Isao | Lee, Dong-Kee | Qin, Jun | Petit, Fabrice G. | Takamoto, Norio | Demayo, Francesco J. | Tsai, Ming-Jer

Edité par CCSD -

International audience. COUP-TFII (Chicken Ovalbumin Upstream Promoter-Transcription Factor II) is an orphan nuclear receptor that belongs to the nuclear receptor superfamily. Genetic ablation of COUP-TFII results in early embryonic lethality due to defects in angiogenesis and heart development. COUP-TFII is expressed in the uterine stroma and is controlled by progesterone-Ihh-Ptch signaling. To assess the uterine function of COUP-TFII, we have ablated COUP-TFII in the uterine stroma by PR-Cre. The uterine specific null mutants are infertile and exhibit defects in blastocyst attachment and decidualization. We identified a genetic pathway in which the epithelial Ihh regulates COUP-TFII to control BMP-2, which then regulates decidualization. Interestingly, enhanced epithelial estrogen activity, which impedes the maturation of a receptive uterus, was noted in the absence of COUP-TFII. This finding reveals that COUP-TFII mediates progesterone signaling to inhibit estrogen activity, and establishes the requirement for epithelia-stromal interaction during the implantation process. COUP-TFII is also expressed in the Leydig cells of male mice. Conditional ablation of COUP-TFII in the male results in infertility due to impairment of spermatogenesis and Leydig cell differentiation. Taken together, COUP-TFII is a critical player for female and male reproduction.HL 076448, U54 H007495 PJ4, DK 62434

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