Expression and regulation of the differentiation regulators ERBB Receptor Feedback Inhibitor 1 (ERRFI1) and Interferon-related Developmental Regulator 1 (IFRD1) during the periovulatory period in the rat ovary

Mol Reprod Dev. 2016 Aug;83(8):714-23. doi: 10.1002/mrd.22673. Epub 2016 Jul 7.


The current study investigated the regulation and the spatiotemporal expression pattern of Errfi1 and Ifrd1, genex encoding factors that regulate differentiation and cessation of cell division, in the rat ovary during the periovulatory period. Immature female rats (22-23 days old) were injected with pregnant-mare serum gonadotropin to stimulate folliculogenesis, followed by human chorionic gonadotropin (hCG) to induce ovulation. Ovaries, granulosa cells, theca-interstitial cells, or cumulus oocyte complexes (COCs) were collected at various times after hCG administration (n = 3 per time point). Expression analysis revealed that Errfi1 and Ifrd1 were highly induced in the ovary, although their spatiotemporal expression differed: In situ hybridization analysis demonstrated that Errfi1 mRNA expression was initially induced in theca-interstitial cells at 4 and 8 hr after hCG, then transitioned to granulosa cells at 12 hr, and decreased in newly forming corpora lutea at 24 hr. Ifrd1 mRNA, on the other hand, was primarily induced in granulosa cells, and expression remained elevated in newly forming corpora lutea. Interestingly, Errfi1 and Ifrd1 were also expressed in the COC, suggesting a potential role in cumulus cell expansion or oocyte maturation. Inhibition of progesterone or prostaglandin synthesis reduced Errfi1 and Ifrd1 transcription, whereas inhibition of epidermal growth factor signaling inhibited only Errfi1 mRNA abundance. Down-regulation of both genes led to further suppression of progesterone. Our findings thus suggest that the stimulation of Errfi1 and Ifrd1 may be important for theca and granulosa cell differentiation and COC expansion. Mol. Reprod. Dev. 83: 714-723, 2016 © 2016 Wiley Periodicals, Inc.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Chorionic Gonadotropin / pharmacology
  • Cumulus Cells / cytology
  • Cumulus Cells / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Immediate-Early Proteins / biosynthesis*
  • Membrane Proteins / biosynthesis*
  • Ovulation / drug effects
  • Ovulation / physiology*
  • Progesterone / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Theca Cells / cytology
  • Theca Cells / metabolism*
  • Tumor Suppressor Proteins / biosynthesis*


  • Chorionic Gonadotropin
  • Ifrd1 protein, rat
  • Immediate-Early Proteins
  • Membrane Proteins
  • Tumor Suppressor Proteins
  • Progesterone