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Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis

  • Endometriosis: Original Article
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Abstract

Although nutrient status plays an important role in cell metabolism, its significance in endometriosis is obscure. Herein, we investigated the effects of a low-nutrient microenvironment on endometriosis. Stromal cells (SCs) from ovarian endometrioma (OESCs) or normal endometrium without endometriosis (NESCs) were isolated and cultured. A low-nutrient microenvironment was replicated by replacing the culture medium with Hank’s balanced salt solution. OESC and NESC proliferation under the low-nutrient condition was measured. The expression of exacerbating factors in endometriosis under the low-nutrient condition was examined at the mRNA and protein levels. OESCs showed higher proliferation than NESCs under the low-nutrient condition. In OESCs, the low-nutrient condition upregulated the mRNA expression of vascular endothelial growth factor (VEGF), interleukin-6 and -8, aromatase, Bcl-2, and peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) and downregulated that of BAX and induced transcription of PI.3, PII, and exon II. Western blotting revealed elevated VEGF and PGC-1α expression under the low-nutrient condition in OESCs. These changes coincided with the elevated expression of PGC-1α, which was reduced at the mRNA level upon nutrient status rescue. Endometriosis is exacerbated by altered angiogenesis, inflammation, anti-apoptosis, and local estrogen production while trying to survive under a low-nutrient microenvironment; it may be attributed to PGC-1α-mediated metabolic mechanisms.

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The data underlying this article will be shared at reasonable request to the corresponding author.

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Acknowledgements

We thank Ms. Ayaka Miura and Ms. Makoto Kazui for providing technical assistance.

Funding

This work was supported partially by Grants-in-Aid for Scientific Research under Grant number [21K09523] from the Ministry of Education, Culture, Sports, Science, and Technology (Japan).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan

    Koki Shimura, Yosuke Tarumi, Maya Fujii, Kanae Ogawa, Eiko Maeda, Yukiko Tanaka, Hiroyuki Okimura, Hisashi Kataoka, Osamu Takaoka, Fumitake Ito, Akemi Koshiba, Khaleque N. Khan, Izumi Kusuki, Jo Kitawaki & Taisuke Mori

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  1. Koki Shimura
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Contributions

K.S., T.M., and J.K. designed the study. K.S., Y.T., M.F., K.O., E.M., Y.T., H.O., H.K., O.T., and Y.T. conceived and carried out experiments. K.S., T.M., F.I., A.K., K.K., and I.K. contributed to the interpretation of the results. K.S. and T.M. wrote the article. All authors were involved in writing the paper and had final approval of the submitted and published version.

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Correspondence to Koki Shimura.

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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and its later amendments. This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine (ERB-C-855–1).

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Supplementary file2

Supplementary Fig. 1 TUNEL staining of ovarian endometrioma stromal cell (OESC) and normal endometrium stromal cell (NESC) under low-nutrient conditions. TUNEL staining was performed after 24 h of incubation in low-nutrient medium, respectively. a, NESCs; b, OESCs; arrows, positive cells; bar, 200 μm. (PNG 2930 kb)

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Supplementary file3

Supplementary Fig. 2 Expression of IL-1β and TNF-α in ovarian endometrioma stromal cell (OESC) under low-nutrient conditions. The expression of them in OESCs (n=6) was measured using real-time polymerase chain reaction (PCR) after incubation with control (Cont) or low-nutrient (Low) medium for 24 h. *P < 0.05 versus Cont (Wilcoxon signed-rank test). Abbreviations: TNF-α, tumor necrosis factor-α (PNG 112 kb)

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Shimura, K., Tarumi, Y., Fujii, M. et al. Low-Nutrient Environment-Induced Changes in Inflammation, Cell Proliferation, and PGC-1α Expression in Stromal Cells with Ovarian Endometriosis. Reprod. Sci. 30, 1094–1102 (2023). https://doi.org/10.1007/s43032-022-01089-5

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