Oligo‐astheno‐teratozoospermia in mice lacking ORP4, a sterol‐binding protein in the OSBP‐related protein family |
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Authors: | Osamu Udagawa Chizuru Ito Narumi Ogonuki Hiroyasu Sato Shoken Lee Pearlta Tripvanuntakul Ikuyo Ichi Yasunori Uchida Taki Nishimura Makoto Murakami Atsuo Ogura Takao Inoue Kiyotaka Toshimori Hiroyuki Arai |
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Institution: | 1. Graduate School of Pharmaceutical Sciences, University of Tokyo, , Tokyo, 113‐0033 Japan;2. Department of Anatomy and Developmental Biology, Graduate School of Medicine, Chiba University, , Chiba, 260‐8670 Japan;3. BioResource Center, RIKEN, , Ibaraki, 305‐0024 Japan;4. Lipid Metabolism Project, Department of Advanced Science for Biomolecules, The Tokyo Metropolitan Institute of Medical Science, , Tokyo, 156‐8506 Japan;5. CREST, Japan Science and Technology Agency (JST), , Tokyo, 102‐0075 Japan |
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Abstract: | Oligo‐astheno‐teratozoospermia (OAT), a condition that includes low sperm number, low sperm motility and abnormal sperm morphology, is the commonest cause of male infertility. Because genetic analysis is frequently impeded by the infertility phenotype, the genetic basis of many of OAT conditions has been hard to verify. Here, we show that deficiency of ORP4, a sterol‐binding protein in the oxysterol‐binding protein (OSBP)‐related protein family, causes male infertility due to severe OAT in mice. In ORP4‐deficient mice, spermatogonia proliferation and subsequent meiosis occurred normally, but the morphology of elongating and elongated spermatids was severely distorted, with round‐shaped head, curled back head or symplast. Spermatozoa derived from ORP4‐deficient mice had little or no motility and no fertilizing ability in vitro. In ORP4‐deficient testis, postmeiotic spermatids underwent extensive apoptosis, leading to a severely reduced number of spermatozoa. At the ultrastructural level, nascent acrosomes appeared to normally develop in round spermatids, but acrosomes were detached from the nucleus in elongating spermatids. These results suggest that ORP4 is essential for the postmeiotic differentiation of germ cells. |
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