• PMID: 12695510
• Gene Name: GPX4
• Condition: Assocaited with inability of the sperm to regulate the cell volume and in abnormal sperm morphology and immotility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Assocaited with inability of the sperm to regulate the cell volume and in abnormal sperm morphology and immotility

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

Andersen OM, Yeung CH, Vorum H, Wellner M, Andreassen TK, Erdmann B, Mueller EC, Herz J, Otto A, Cooper TG, Willnow TE.

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. FAU - Andersen, Olav M AU - Andersen OM AD - Max-Delbrueck-Center for Molecular Medicine and Medical Faculty of the Free University, D-13125 Berlin, Germany. FAU - Yeung, Ching-Hei AU - Yeung CH FAU - Vorum, Henrik AU - Vorum H FAU - Wellner, Maren AU - Wellner M FAU - Andreassen, Thomas K AU - Andreassen TK FAU - Erdmann, Bettina AU - Erdmann B FAU - Mueller, Eva-Christina AU - Mueller EC FAU - Herz, Joachim AU - Herz J FAU - Otto, Albrecht AU - Otto A FAU - Cooper, Trevor G AU - Cooper TG