JZUS - Journal of Zhejiang University SCIENCE

Journal of Zhejiang University SCIENCE B

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High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression in ovarian hyperstimulation in mice

Author(s): Quanmin KANG, Fang LE, Xiayuan XU, Lifang CHEN, Shi ZHENG, Lijun LOU, Nan JIANG, Ruimin ZHAO, Yuanyuan ZHOU, Juan SHEN, Minhao HU, Ning WANG, Qiongxiao HUANG, Fan JIN
Affiliation(s): Department of Reproductive Endocrinology, Key Laboratory of Reproductive Genetics of National Ministry of Education, Women’s Reproductive Health Laboratory of Zhejiang Province, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, P. R. China; more
Corresponding email(s): jinfan@zju.edu.cn, huangqiongxiao@hmc.edu.cn
Key Words: Ovarian stimulation; Histone methylation; Assisted reproductive technology (ART)

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Quanmin KANG, Fang LE, Xiayuan XU, Lifang CHEN, Shi ZHENG, Lijun LOU, Nan JIANG, Ruimin ZHAO, Yuanyuan ZHOU, Juan SHEN, Minhao HU, Ning WANG, Qiongxiao HUANG, Fan JIN. High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression in ovarian hyperstimulation in mice[J]. Journal of Zhejiang University Science B,in press.Frontiers of Information Technology & Electronic Engineering,in press.https://doi.org/10.1631/jzus.B2300681

@article{title="High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression in ovarian hyperstimulation in mice",
author="Quanmin KANG, Fang LE, Xiayuan XU, Lifang CHEN, Shi ZHENG, Lijun LOU, Nan JIANG, Ruimin ZHAO, Yuanyuan ZHOU, Juan SHEN, Minhao HU, Ning WANG, Qiongxiao HUANG, Fan JIN",
journal="Journal of Zhejiang University Science B",
year="in press",
publisher="Zhejiang University Press & Springer",
doi="https://doi.org/10.1631/jzus.B2300681"
}

%0 Journal Article
%T High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression in ovarian hyperstimulation in mice
%A Quanmin KANG
%A Fang LE
%A Xiayuan XU
%A Lifang CHEN
%A Shi ZHENG
%A Lijun LOU
%A Nan JIANG
%A Ruimin ZHAO
%A Yuanyuan ZHOU
%A Juan SHEN
%A Minhao HU
%A Ning WANG
%A Qiongxiao HUANG
%A Fan JIN
%J Journal of Zhejiang University SCIENCE B
%P
%@ 1673-1581
%D in press
%I Zhejiang University Press & Springer
doi="https://doi.org/10.1631/jzus.B2300681"

TY - JOUR
T1 - High-dose estrogen impairs demethylation of H3K27me3 by decreasing Kdm6b expression in ovarian hyperstimulation in mice
A1 - Quanmin KANG
A1 - Fang LE
A1 - Xiayuan XU
A1 - Lifang CHEN
A1 - Shi ZHENG
A1 - Lijun LOU
A1 - Nan JIANG
A1 - Ruimin ZHAO
A1 - Yuanyuan ZHOU
A1 - Juan SHEN
A1 - Minhao HU
A1 - Ning WANG
A1 - Qiongxiao HUANG
A1 - Fan JIN
J0 - Journal of Zhejiang University Science B
SP -
EP -
%@ 1673-1581
Y1 - in press
PB - Zhejiang University Press & Springer
ER -
doi="https://doi.org/10.1631/jzus.B2300681"

Abstract
Chinese Summary
Academic Network
Reviewer Comment

Abstract: Given that ovarian stimulation is vital for assisted reproductive technology (ART), and results in elevated serum estrogen levels, exploring the impact of elevated estrogen exposure on oocytes and embryos is necessary. We investigated the effects of various ovarian stimulation treatments on oocyte and embryo morphology and gene expression using a mouse model and estrogen-treated mouse embryonic stem cells (mESCs). Female C57BL/6J mice were subjected to two types of conventional ovarian stimulation and ovarian hyperstimulation; mice treated with only normal saline served as controls. Hyperstimulation resulted in high serum estrogen levels, enlarged ovaries, an increased number of aberrant oocytes, and decreased embryo formation. mRNA-sequencing of oocytes revealed the dysregulated expression of Lysine (K)-specific demethylase 6b (Kdm6b), which may be a key factor indicating hyperstimulation-induced aberrant oocytes and embryos. In vitro, Kdm6b expression was downregulated in mESCs treated with high-dose estrogen; treatment with an estrogen receptor antagonist could reverse this downregulated expression level. Furthermore, treatment with high-dose estrogen resulted in the upregulated expression of histone H3 lysine 27 trimethylation (H3K27me3) and γ-H2AX. Notably, knockdown of Kdm6b and high estrogen levels hindered the formation of embryoid bodies, with a concomitant increase in the expression of H3K27me3 and γ-H2AX. Collectively, our findings revealed that hyperstimulation-induced high-dose estrogen could impair the demethylation of H3K27me3 by reducing Kdm6b expression. Accordingly, Kdm6b could be a promising marker for predicting clinically ART outcomes in patients with ovarian hyperstimulation syndrome.

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