Versican provides the provisional matrix for uterine spiral artery dilation and fetal growth

作者：Yusuke Sagae, Akihito Horie, Akihiro Yanai, Tsutomu Ohara, Baku Nakakita, Yoshimi Kitawaki, Asuka Okunomiya, Hirohiko Tani, Ken D Yamaguchi, Junzo Hamanishi, John P. Lydon, Takiko Daikoku, Hideto Watanabe, Masaki Mandai · 发表于：Matrix Biology · 年份：2022 · DOI：10.1016/j.matbio.2022.11.004 · 被引用次数：10 · 研究领域：Reproductive System and Pregnancy、Pregnancy and preeclampsia studies、Endometriosis Research and Treatment

The extracellular matrix (ECM) in the endometrium plays a crucial role in mammalian pregnancy. We have shown that versican secreted from the endometrial epithelium promotes embryo implantation. Versican is a proteoglycan, a major player in the provisional matrix, and versikine, its N-terminal fragment cleaved by ADAMTS proteinases, serves as a bioactive molecule. Here, since versican expression in the placenta was dynamically altered in humans and mice, we investigated the role of versican in pregnancy using uterine-specific Vcan deletion mice (uKO mice) and ADAMTS-resistant versican expressing mice (V1R mice). uKO mice exhibited insufficient spiral artery dilation, followed by fetal growth restriction and maternal hypertension. Further analysis revealed impaired proliferation of tissue-resident natural killer cells required for spiral artery dilation. V1R mice showed the same results as the control, eliminating the involvement of versikine. Our results provide a new concept that versican, one factor of ECM, contributes to placentation and following fetal growth.