Essential role of the apolipoprotein E receptor-2 in sperm development

Olav M. Andersen, Ching Hei Yeung, Henrik Vorum, Maren Wellner, Thomas K. Andreassen, Bettina Erdmann, Eva Christina Mueller, Joachim Herz, Albrecht Ott, Trevor G. Coopers, Thomas E. Willnow

Research output: Contribution to journalArticlepeer-review

94 Scopus citations


The apolipoprotein (apo) E receptor-2 (apoER2) is a member of the low density lipoprotein receptor gene family and an important regulator of neuronal migration. It acts as a receptor for the signaling factor Reelin and provides positional cues to neurons that migrate to their proper position in the developing brain. Besides brain formation defects, apoER2-deficient mice also exhibit male infertility. The role of the receptor in male reproduction, however, remained unclear. Here we demonstrate that apoER2 is highly expressed in the initial segment of the epididymis, where it affects the functional expression of clusterin and phospholipid hydroperoxide glutathione peroxidase (PHGPx), two proteins required for sperm maturation. Reduced PHGPx expression in apoER2 knockout mice results in the inability of the sperm to regulate the cell volume and in abnormal sperm morphology and immotility. Because insufficient expression of PHGPx is a major cause of infertility in men, these findings not only highlight an important new function for apoER2 that is unrelated to neuronal migration, but they also suggest a possible role for apoER2 in human infertility.

Original languageEnglish (US)
Pages (from-to)23989-23995
Number of pages7
JournalJournal of Biological Chemistry
Issue number26
StatePublished - Jul 27 2003

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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