Membrane protein CD9 is repositioned and released to enhance uterine function

Maki Iwai, Toshio Hamatani, Akihiro Nakamura, Natsuko Kawano, Seiya Kanai, Woojin Kang, Noriko Yoshii, Yasushi Odawara, Mitsutoshi Yamada, Yoshitaka Miyamoto, Takakazu Saito, Hidekazu Saito, Mami Miyado, Akihiro Umezawa, Kenji Miyado, Mamoru Tanaka

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Tetraspanin CD9 is essential for sperm–egg fusion and also contributes to uterine repair through microexosome formation. Microexosomes share CD9 with exosomes and are released from eggs and uterine epithelial cells. However, the mechanism for the formation of microexosomes remains unknown. To address this issue, we examined membrane localization and extracellular release of CD9 proteins using uterine epithelial cells and secretions in mice and humans. In mice, CD9 localized predominantly on the basal region of the plasma membrane and relocated to the apical region upon embryo implantation. Furthermore, extracellular CD9 proteins were detected in uterine secretions of mice and women undergoing infertility treatment, but were below detectable levels in supernatants of pluripotent stem cells. Ultrastructural analysis demonstrated that membrane projections were shortened and the number of mitochondria was reduced in uterine epithelial cells lacking Cd9 genes. Our results suggest that CD9 repositioning and release affect both membrane structures and mitochondrial state in the uterus, and contribute to female fertility.

Original languageEnglish
Pages (from-to)200-209
Number of pages10
JournalLaboratory Investigation
Volume99
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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    Iwai, M., Hamatani, T., Nakamura, A., Kawano, N., Kanai, S., Kang, W., Yoshii, N., Odawara, Y., Yamada, M., Miyamoto, Y., Saito, T., Saito, H., Miyado, M., Umezawa, A., Miyado, K., & Tanaka, M. (2019). Membrane protein CD9 is repositioned and released to enhance uterine function. Laboratory Investigation, 99(2), 200-209. https://doi.org/10.1038/s41374-018-0145-1