Core binding factor-β knockdown alters ovarian gene expression and function in the mouse

Kalin Wilson, Jiyeon Park, Thomas E. Curry, Birendra Mishra, Jan Gossen, Ichiro Taniuchi, Misung Jo

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Core binding factor (CBF) is a heterodimeric transcription factor complex composed of a DNAbinding subunit, one of three runt-related transcription factor (RUNX) factors, and a non-DNA binding subunit, CBFβ. CBFβ is critical for DNA binding and stability of the CBF transcription factor complex. In the ovary, the LH surge increases the expression of Runx1 and Runx2 in periovulatory follicles, implicating a role for CBFs in the periovulatory process. The present study investigated the functional significance of CBFs (RUNX1/CBFβ and RUNX2/CBFβ) in the ovary by examining the ovarian phenotype of granulosa cell-specific CBFβ knockdown mice; CBFβ f/f * Cyp19 cre. The mutant female mice exhibited significant reductions in fertility, with smaller litter sizes, decreased progesterone during gestation, and fewer cumulus oocyte complexes collected after an induced superovulation. RNA sequencing and transcriptome assembly revealed altered expression of more than 200 mRNA transcripts in the granulosa cells of Cbfb knockdown mice after human chorionic gonadotropin stimulation in vitro. Among the affected transcripts are known regulators of ovulation and luteinization including Sfrp4, Sgk1, Lhcgr, Prlr, Wnt4, and Edn2 as well as many genes not yet characterized in the ovary. Cbfβ knockdown mice also exhibited decreased expression of key genes within the corpora lutea and morphological changes in the ovarian structure, including the presence of large antral follicles well into the luteal phase. Overall, these data suggest a role for CBFs as significant regulators of gene expression, ovulatory processes, and luteal development in the ovary.

Original languageEnglish
Pages (from-to)733-747
Number of pages15
JournalMolecular Endocrinology
Volume30
Issue number7
DOIs
StatePublished - Jul 2016

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health (NIH) Grants RO1HD061617, RO3HD066012, and PO1HD71875.

Publisher Copyright:
© 2016 by the Endocrine Society.

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

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