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Molecular Endocrinology, doi:10.1210/me.2005-0019
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Molecular Endocrinology 19 (9): 2299-2308
Copyright © 2005 by The Endocrine Society

Haploinsufficiency of Chicken Ovalbumin Upstream Promoter Transcription Factor II in Female Reproduction

Norio Takamoto, Isao Kurihara, Kevin Lee, Francesco J. DeMayo, Ming-Jer Tsai and Sophia Y. Tsai

Department of Molecular and Cellular Biology and Program of Development, Baylor College of Medicine, Houston, Texas 77030

Address all correspondence and requests for reprints to: Sophia Y. Tsai, Ph.D., and Ming-Jer Tsai, Ph.D., Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030. E-mail: stsai{at}bcm.tmc.edu or mtsai{at}bcm.tmc.edu.

The chicken ovalbumin upstream promoter transcription factor II, COUP-TFII, is a member of the orphan nuclear receptor transcription factor family. Genetic ablation of COUP-TFII results in early embryonic lethality and demonstrates that this gene is required for cardiac and vascular development. Expression of COUP-TFII persists throughout postnatal life in various tissues including the female reproductive tract. However, the physiological function of COUP-TFII in female reproduction has not been extensively analyzed. Here, we provide phenotypic evidences that haploinsufficiency of COUP-TFII in mice demonstrates an important role of COUP-TFII for normal female reproduction. COUP-TFII +/– females show significantly reduced fecundity, irregular estrus cycles, delayed puberty, and retarded postnatal growth. Analysis of the reduced fertility revealed that although ovarian function was normal with respect to ovulation, the ovaries have reduced ability to synthesize progesterone in response to exogenous gonadotropins. This reduction is due to the reduction of the expression of steroidogenic enzymes important for progesterone synthesis and the reduction of vascularization in COUP-TFII heterozygotes. Analysis of uterine function demonstrated a reduced response to an experimentally induced decidual cell reaction indicating that the ability of the uterus to support embryo implantation was reduced. Taken together, our data show global impact of gene dosage effects of COUP-TFII on female postnatal life and indicates requirement of COUP-TFII in normal female reproduction, in particular for uterine endometrial functions during the periimplantation period.

NURSA Molecule Pages Link:

Nuclear Receptors:   COUP-TFII



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