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Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells

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Abstract

Clinical trials have shown that administering heparin during the luteal phase has beneficial effects on implantation and live birth rates. Heparin exerts direct effects on decidual human endometrial stromal cells (HESCs), which are independent of its anticoagulant effect. However, the accurate effects of heparin on the decidualization process remain unidentified. Here, we demonstrate that HESCs become dramatically resistant to oxidative stress upon decidualization, and we hypothesize a possible direct action of heparin on the decidualization of HESCs, which would lead to improved implantation. To test this hypothesis, we established primary HESC cultures and propagated them, and then we decidualized confluent cultures with 8-bromo-cAMP, with medroxyprogesterone acetate, and with or without heparin. We treated the cells with hydrogen peroxide (H2O2) as a source of reactive oxygen species (ROS). Adding heparin to decidualized HESCs induced prolactin secretion. Decidualized HESCs treated with heparin were prevented from undergoing apoptosis induced by oxidative stress. Heparin induced nuclear accumulation of the forkhead transcription factor FOXO1 and expression of its downstream target, the ROS scavenger superoxide dismutase 2. These results demonstrate that heparin-treated decidualized HESCs acquired further resistance to oxidative stress, suggesting that heparin may improve the implantation environment.

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Acknowledgements

We would like to thank Ms. S. Mitsui for her assistance with experiments. This work was supported by JSPS KAKENHI (Grant numbers 17K11250 and 16K20204).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan

    Shunsuke Tamaru, Takeshi Kajihara, Yumi Mizuno, Natsuko Takano, Hideno Tochigi, Tomomi Sato & Osamu Ishihara

  2. Department of Anatomy, Saitama Medical University, 38 Morohongo, Moroyama, Iruma-gun, Saitama, 350-0495, Japan

    Tomomi Sato

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  1. Shunsuke Tamaru
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  2. Takeshi Kajihara
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Correspondence to Takeshi Kajihara.

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Tamaru, S., Kajihara, T., Mizuno, Y. et al. Heparin prevents oxidative stress-induced apoptosis in human decidualized endometrial stromal cells. Med Mol Morphol 52, 209–216 (2019). https://doi.org/10.1007/s00795-019-00220-x

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