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

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 fragme...

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Bibliographic Details
Published in:Matrix biology 2023-01, Vol.115, p.16-31
Main Authors: Sagae, Yusuke, Horie, Akihito, Yanai, Akihiro, Ohara, Tsutomu, Nakakita, Baku, Kitawaki, Yoshimi, Okunomiya, Asuka, Tani, Hirohiko, Yamaguchi, Ken, Hamanishi, Junzo, Lydon, John P., Daikoku, Takiko, Watanabe, Hideto, Mandai, Masaki
Format: Article
Language:English
Subjects:
Animals
Arteries - metabolism
Dilatation
Extracellular matrix
Female
Fetal Development
Fetal growth restriction
Humans
Mammals - metabolism
Mice
Preeclampsia
Pregnancy
Spiral artery
Uterine NK cell
Uterus - metabolism
Versican
Versicans - genetics
Versicans - metabolism
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Summary: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. [Display omitted]
ISSN:0945-053X
1569-1802
DOI:10.1016/j.matbio.2022.11.004