☆ 4.7 Article

Down-Regulation of S100A11, a Calcium-Binding Protein, in Human Endometrium May Cause Reproductive Failure

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2012)

Journal

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM

Volume 97, Issue 10, Pages 3672-3683

Publisher

ENDOCRINE SOC

DOI: 10.1210/jc.2012-2075

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Funding

National Key Technology R&D Program of China [2012BAI32B00]
National Basic Research Program of China [2012CB944901, 2011CB944502]
Zhejiang Provincial Natural Science Foundation of China [LY12H04008]

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Abstract

Background: Low expression levels of S100A11 proteins were demonstrated in the placental villous tissue of patients with early pregnancy loss, and S100A11 is a Ca2+-binding protein that interprets the calcium fluctuations and elicits various cellular responses. Objectives: The objective of the study was to determine S100A11 expression in human endometrium and its roles in endometrial receptivity and embryo implantation. Methods: S100A11 expression in human endometrium was analyzed using quantitative RT-PCR, Western blot, and immunohistochemical techniques. The effects of S100A11 on embryo implantation were examined using in vivo mouse model, and JAr (a human choriocarcinoma cell line) spheroid attachment assays. The effects of endometrial S100A11 on factors related to endometrial receptivity and immune responses were examined. Using a fluorescence method, we examined the changes in cytosolic Ca2+ and Ca2+ release from intracellular stores in epidermal growth factor (EGF)-treated endometrial cells transfected with or without S100A11 small interfering RNA. Results: S100A11 was expressed in human endometrium. S100A11 protein levels were significantly lower in endometrium of women with failed pregnancy than that in women with successful pregnancy outcomes. The knockdown of endometrial S100A11 not only reduced embryo implantation rate in mouse but also had adverse effects on the expression of factors related to endometrial receptivity and immune responses in human endometrial cells. Immunofluorescence analysis showed that S100A11 proteins were mainly localized in endoplasmic reticulum. The EGF up-regulated endometrial S100A11 expression and promoted the Ca2+ uptake and release from Ca2+ stores, which was inhibited by the knockdown of S100A11. Conclusions: Endometrial S100A11 is a crucial intermediator in EGF-stimulated embryo adhesion, endometrium receptivity, and immunotolerance via affecting Ca2+ uptake and release from intracellular Ca2+ stores. Down-regulation of S100A11 may cause reproductive failure. (J Clin Endocrinol Metab 97: 3672-3683, 2012)

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NRSF-GNAO1 Pathway Contributes to the Regulation of Cardiac Ca2+ Homeostasis

Hideaki Inazumi, Koichiro Kuwahara, Yasuaki Nakagawa, Yoshihiro Kuwabara, Takuro Numaga-Tomita, Toshihide Kashihara, Tsutomu Nakada, Nagomi Kurebayashi, Miku Oya, Miki Nonaka, Masami Sugihara, Hideyuki Kinoshita, Kenji Moriuchi, Hiromu Yanagisawa, Toshio Nishikimi, Hirohiko Motoki, Mitsuhiko Yamada, Sachio Morimoto, Kinya Otsu, Richard M. Mortensen, Kazuwa Nakao, Takeshi Kimura

Summary: NRSF is a transcriptional repressor that suppresses the reactivation of fetal cardiac gene program and maintains cardiac integrity. This study reveals that NRSF regulates ventricular function by controlling the expression of G alpha(o) gene, and excessive expression of G alpha(o) leads to cardiac dysfunction. Additionally, G alpha(o) plays a critical role in cardiac Ca2+ homeostasis and systolic function.

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