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Low temperature plasma protects against inflammatory agents-mediated dysfunction of theca cells via enhancing MANF expression

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Abstract

Background

Low temperature plasma (LTP) exerts a protective effect in inflammation via enhancing MANF expression. Hyperactivation and dysfunction of theca cells induced by inflammatory agents is accompanied by polycystic ovary syndrome (PCOS), which is a common reproductive and endocrine disorder. However, the effect of LTP on theca cells is still unknown.

Methods and results

Theca cells were stimulated with IL-1β or TNF-α for 12 h, then treated with LTP for 100 s. After 8 h, medium supernatant and theca cells were collected. Production of androgen from theca cells were detected by ELISA. The PCNA and Annexin V levels in theca cells were detected by using immunofluorescent staining. The levels of PCNA, BCL-2 and BAX were evaluated by western blot and qPCR. MTT assay was used to detect the viability of theca cells. The proportions of apoptosis of theca cells were detected by Flow cytometry. The mRNA levels of androgenic genes were detected by qPCR. The MANF levels in medium supernatant and cell lysate were detected by using ELISA, western and qPCR. BIP and CHOP expressions were detected by using western blot and qPCR. We found that LTP irradiation decreased inflammatory agents-induced upregulation of androgen and androgenic genes in theca cells. And LTP irradiation relieves IL-1β or TNF-α-induced pathological proliferation and apoptosis in theca cells. In terms of mechanism, LTP irradiation increased MANF level in theca cells to inhibit BIP and CHOP expression.

Conclusion

These evidences suggest the protective effect of LTP on theca cells in inflammatory microenvironment, and LTP has the potential clinical application of PCOS.

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Data availability

All data are available from the corresponding author on reasonable request.

Abbreviations

BAX:

BCL2-associated X protein

Bcl-2:

B-cell lymphoma-2

HMGCR:

Hydroxylmethylglutaryl-CoA reductase

ER:

Endoplasmic reticulum

LTP:

Low temperature plasma

MANF:

Mesencephalic astrocyte-derived neurotrophic factor

PCNA:

Proliferating Cell Nuclear Antigen

PCOS:

Polycystic ovary syndrome

ROS:

Reactive oxygen species

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Acknowledgements

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Funding

This study was supported by the Joint Construction Project of Obstetrics and Gynecology and Maternal, Child and Adolescent Health [Grant Number 2021lcxk016].

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Author notes

  1. ShuJun Yu and XinRu Zhang contributed equally to this work.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Reproductive Medicine Center, The First Affiliated Hospital of Anhui Medical University, No 218 Jixi Road, Hefei, 230022, Anhui, China

    ShuJun Yu & ZhaoLian Wei

  2. NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China

    ShuJun Yu & ZhaoLian Wei

  3. Anhui Province Key Laboratory of Reproductive Health and Genetics, No 81 Meishan Road, Hefei, 230032, Anhui, China

    ShuJun Yu & ZhaoLian Wei

  4. School of Basic Medical Sciences, Anhui Medical University, 81 Meishan Road, Hefei, 230032, Anhui, China

    XinRu Zhang, Tao Sun & Dong Wang

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  2. XinRu Zhang
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ZLW and DW designed the study and supervised the experiments. SJY and XRZ performed the experiments, analyzed the data and wrote the manuscript. TS performed the experiments.

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Correspondence to Dong Wang or ZhaoLian Wei.

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Yu, S., Zhang, X., Sun, T. et al. Low temperature plasma protects against inflammatory agents-mediated dysfunction of theca cells via enhancing MANF expression. Mol Biol Rep 50, 3085–3097 (2023). https://doi.org/10.1007/s11033-022-08185-4

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