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Lab Invest. 2018 Nov 6. doi: 10.1038/s41374-018-0145-1. [Epub ahead of print]

Membrane protein CD9 is repositioned and released to enhance uterine function.

Author information

1
Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan.
2
Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
3
Department of Obstetrics and Gynecology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, 160-8582, Japan. toshiohamatani@z3.keio.jp.
4
Department of Life Sciences, School of Agriculture, Meiji University, 1-1-1 Higashimita, Kawasaki, Kanagawa, 214-8571, Japan.
5
Department of Perinatal Medicine and Maternal Care, National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
6
Tokyo Adventist Hospital Megumi Clinic, 3-5-2 Amanuma, Suginami, Tokyo, 167-0032, Japan.
7
Fertility Clinic Tokyo, 3-13-11 Higashi, Shibuya, Tokyo, 150-0011, Japan.
8
Department of Molecular Endocrinology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan.
9
Department of Reproductive Biology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan. miyado-k@ncchd.go.jp.

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.

PMID:
30401958
DOI:
10.1038/s41374-018-0145-1

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