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Tanshinone IIA increased amniotic fluid volume through down-regulating placental AQPs expression via inhibiting the activity of GSK-3β

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Abstract

The mechanism of idiopathic oligohydramnios is still uncertain, and there is no effective and targeted treatment for it. Placental aquaporins (AQPs) were associated with idiopathic oligohydramnios. This study aimed to investigate the effect of tanshinone IIA on amniotic fluid volume (AFV) and its underlying molecular mechanisms related to placental AQPs (AQP1, AQP3, AQP8, AQP9). Results showed that compared with the women with normal AFV, placental AQP1, AQP3, AQP8, and AQP9 protein expressions were decreased in women with idiopathic oligohydramnios. Immunohistochemistry revealed localization of AQP1, AQP3, AQP8, and AQP9 mainly in trophoblast cells within labyrinth zone of mouse placenta. Also, AQP1 was located in fetal vascular endothelial cells. Pregnant mice were administered with tanshinone IIA (10 mg/kg or 50 mg/kg, n = 8, respectively) or vehicle (n = 8) from 9.5 to 18.5 gestational day (GD). Tanshinone IIA markedly increased the AFV in pregnant mice, without the effects on embryo numbers per litter, atrophic embryo rate, fetal weight, and placental weight, as well as increased the expressions of AQPs and inhibited the activity of GSK-3β in mice placenta. In JEG-3 cells, tanshinone IIA downregulated AQP1, AQP3, AQP8, AQP9 expressions and inhibited the activity of GSK-3β. Activating GSK-3β with MK-2206 eliminated these alterations. Thus, tanshinone IIA could increase AFV in pregnant mice, possibly through downregulating placental AQP1, AQP3, AQP8, and AQP9 expression via inhibiting the activity of GSK-3β. Tanshinone IIA may be optional for the treatment of idiopathic oligohydramnios.

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Acknowledgements

We would like to thank all the authors’ work and the financial support by grants from the Project of Zhejiang Province Medical and Health Science, Technology Plan and the Science and Technology Bureau of Wenzhou and the Obstetrics and gynecology of combine traditional Chinese and Western medicine of Zhejiang Province. The study sponsors were not involved in the study collection, analysis and interpretation of data, or the writing of the article.

Funding

The work was supported by the Project of Zhejiang Province Medical and Health Science and Technology Plan (2021KY215), the Science and Technology Bureau of Wenzhou (Y20210026) and the Obstetrics and gynecology of combine traditional Chinese and Western medicine of Zhejiang Province (2017-XK-A42).

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  1. Hailing Shao and Shuangjia Pan these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, the Second Affiliated Hospital of Wenzhou Medical University, 325027, Wenzhou, China

    Hailing Shao, Shuangjia Pan, Yehui Lan & Ying Hua

  2. Taizhou Women and Childrens Hospital of Wenzhou Medical University, Taizhou, China

    Xianjun Chen

  3. Department of Obstetrics and Gynecology, The Wenzhou Third Clinical Institute Affiliated To Wenzhou Medical University, Wenzhou, China

    Dongru Dai & Lingli Peng

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  1. Hailing Shao
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  2. Shuangjia Pan
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Contributions

HL. S. and SJ. P. contributed equally to this work. HL.S. designed and performed the experiments, drafted the article; SJ. P. performed the experiments and revised the article; YH. L. and XJ. C. collected the clinical specimens and analyzed the data; DR. D. and LL.P. analyzed the data; Y. H. revised the article critically for important intellectual content and final approval of the version to be published.

Corresponding author

Correspondence to Ying Hua.

Ethics declarations

Research involving human participants and animals

The research involving human was performed in accordance with the Declaration of Helsinki and was approved by the Research Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (No.2016–28). The Animal experiment obtained ethics approval from the Laboratory Animal Ethics Committee of Wenzhou Medical University (No. wydw2019-0260).

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Shao, H., Pan, S., Lan, Y. et al. Tanshinone IIA increased amniotic fluid volume through down-regulating placental AQPs expression via inhibiting the activity of GSK-3β. Cell Tissue Res 389, 547–558 (2022). https://doi.org/10.1007/s00441-022-03646-5

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