Modulation of the Notch System in Response to Wnt Inhibition Induces Restoration of the Rat Luteal Function

Reprod Sci. 2020 Feb;27(2):503-512. doi: 10.1007/s43032-019-00043-2. Epub 2020 Jan 6.

Abstract

The aim of this study was to investigate whether the Notch pathway is modulated in response to the downregulation of the Wnt/Β-catenin system in corpora lutea (CLs) from superovulated rats. To this end, we analyzed the effect of in vitro CL Wnt/Β-catenin inhibition on the expression of Notch members and on luteal function. Mechanically isolated rat CLs were cultured with ICG-001, a Wnt/B-catenin inhibitor. In this system, Wnt/B-catenin inhibition reduced progesterone production and decreased StAR protein levels. Besides, Wnt/B-catenin inhibition stimulated the Notch system, evidenced by an increase in Hes1 expression, and promoted the expression of selected Notch family members. At long incubation times, StAR levels and progesterone concentration reached the control values, effects probably mediated by the Notch pathway. These results provide the first evidence of a compensatory mechanism between Wnt/B-catenin signaling and the Notch system, which contributes to the homeostasis of luteal cells.

Keywords: Corpus luteum; HES1; Notch; StAR; WNT/B-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Luteum / metabolism*
  • Cyclin D1 / metabolism
  • Down-Regulation
  • Female
  • Phosphoproteins / metabolism
  • Progesterone / metabolism
  • Rats, Sprague-Dawley
  • Receptors, Notch / metabolism*
  • Transcription Factor HES-1 / metabolism
  • Wnt Signaling Pathway*

Substances

  • Ccnd1 protein, rat
  • Hes1 protein, rat
  • Phosphoproteins
  • Receptors, Notch
  • Transcription Factor HES-1
  • steroidogenic acute regulatory protein
  • Cyclin D1
  • Progesterone