Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction

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

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2299-2308
Number of pages10
JournalMolecular Endocrinology
Volume19
Issue number9
DOIs
Publication statusPublished - 2005 Sep
Externally publishedYes

Fingerprint

COUP Transcription Factor II
Haploinsufficiency
Reproduction
Progesterone
Fertility
Delayed Puberty
Orphan Nuclear Receptors
Gene Dosage
Estrus
Heterozygote
Ovulation
Gonadotropins
Uterus
Blood Vessels
Ovary
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

Cite this

Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. / Takamoto, Norio; Kurihara, Isao; Lee, Kevin; DeMayo, Francesco J.; Tsai, Ming Jer; Tsai, Sophia Y.

In: Molecular Endocrinology, Vol. 19, No. 9, 09.2005, p. 2299-2308.

Research output: Contribution to journalArticle

Takamoto, Norio ; Kurihara, Isao ; Lee, Kevin ; DeMayo, Francesco J. ; Tsai, Ming Jer ; Tsai, Sophia Y. / Haploinsufficiency of chicken ovalbumin upstream promoter transcription factor II in female reproduction. In: Molecular Endocrinology. 2005 ; Vol. 19, No. 9. pp. 2299-2308.
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