Excess cholesterol induces mouse egg activation and may cause female infertility

Ayce Yesilaltay, Gregoriy A. Dokshin, Dolores Busso, Li Wang, Dalia Galiani, Tony Chavarria, Eliza Vasile, Linda Quilaqueo, Juan Andrés Orellana, Dalia Walzer, Ruth Shalgi, Nava Dekel, David F. Albertini, Attilio Rigotti, David C. Page, Monty Krieger*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

The HDL receptor scavenger receptor, class B type I (SR-BI) controls the structure and fate of plasma HDL. Female SR-BI KO mice are infertile, apparently because of their abnormal cholesterol-enriched HDL particles. We examined the growth and meiotic progression of SR-BI KO oocytes and found that they underwent normal germinal vesicle breakdown; however, SR-BI KO eggs, which had accumulated excess cholesterol in vivo, spontaneously activated, and they escapedmetaphase II (MII) arrest and progressed to pronuclear, MIII, and anaphase/telophase III stages. Eggs from fertile WT mice were activated when loaded in vitro with excess cholesterol by a cholesterol/methyl-β-cyclodextrin complex, phenocopying SR-BI KO oocytes. In vitro cholesterol loading of eggs induced reduction in maturation promoting factor and MAPK activities, elevation of intracellular calcium, extrusion of a second polar body, and progression to meiotic stages beyond MII. These results suggest that the infertility of SR-BI KO females is caused, at least in part, by excess cholesterol in eggs inducing premature activation and that cholesterol can activate WTmouse eggs to escape from MII arrest. Analysis of SR-BI KO female infertility raises the possibility that abnormalities in cholesterol metabolism might underlie some cases of human female infertility of unknown etiology.

Original languageEnglish
Article numberA66
Pages (from-to)E4972-E4980
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number46
DOIs
StatePublished - 18 Nov 2014
Externally publishedYes

Keywords

  • Cholesterol
  • Egg
  • Fertility
  • HDL
  • Meiosis

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