Subfertility with defective folliculogenesis in female mice lacking testicular orphan nuclear receptor 4

Lu Min Chen, Ruey Sheng Wang, Yi Fen Lee, Ning Chun Liu, Yu Jia Chang, Cheng Chia Wu, Shaozhen Xie, Yao Ching Hung, Chawnshang Chang

Research output: Contribution to journalArticlepeer-review

34 Citations (Scopus)


Testicular orphan nuclear receptor 4 (TR4) plays essential roles for normal spermatogenesis in male mice. However, its roles in female fertility and ovarian function remain largely unknown. Here we found female mice lacking TR4 (TR4-/-) displayed subfertility and irregular estrous cycles. TR4-/- female mice ovaries were smaller with fewer or no preovulatory follicles and corpora lutea. After superovulation, TR4-/- female mice produced fewer oocytes, preovulatory follicles, and corpora lutea. In addition, more intensive granulosa apoptosis was found in TR4-/- ovaries. Functional analyses suggest that subfertility in TR4-/- female mice can be due to an ovarian defect with impaired folliculogenesis rather than a deficiency in pituitary gonadotropins. Molecular mechanism dissection of defective folliculogenesis found TR4 might induce LH receptor (LHR) gene expression via direct binding to its 5′ promoter. The consequence of reduced LHR expression in TR4-/- female mice might then result in reduced gonadal sex hormones via reduced expression of enzymes involved in steroido-genesis. Together, our results showed TR4 might play essential roles in normal folliculogenesis by influencing LHR signals. Modulation of TR4 expression and/or activation via its upstream signals or unidentified ligand(s) might allow us to develop small molecule(s) to control folliculogenesis.

Original languageEnglish
Pages (from-to)858-867
Number of pages10
JournalMolecular Endocrinology
Issue number4
Publication statusPublished - Apr 2008

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology


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