Dietary glycotoxins, advanced glycation end products, inhibit cell proliferation and progesterone secretion in ovarian granulosa cells and mimic PCOS-like symptoms

Po Han Lin, Chih Chao Chang, Kun Hsuan Wu, Chun Kuang Shih, Wenchang Chiang, Hsin Yuan Chen, Yin Hwa Shih, Kei Lee Wang, Yong Han Hong, Tzong Ming Shieh, Shih Min Hsia

研究成果: 雜誌貢獻文章

摘要

Women with polycystic ovary syndrome (PCOS) have been reported to have an elevated serum advanced glycation end product (AGE) level. However, the effect of AGEs on the pathophysiological ovarian granulosa cells of PCOS is still unclear. In this study, five indented BSA-derived AGE products were used to evaluate their effect on the function of human granulosa cells. We found that the proliferation of both primary human ovarian granulosa (hGC) cells and human granulosa-like tumor (KGN) cells were inhibited by treatment with these five AGE products. The progesterone secretion level was also reduced in both hGC and KGN cells by treatment with these AGE products through downregulation of LH receptor/cAMP regulatory activity. The granulosa cell layer and serum progesterone level were reduced in rats by treatment with MG-BSA; moreover, an increased number of follicle cysts and an irregular estrous cycle were observed. MG-BSA treatment had a similar effect on the phenotypes of the DHEA-induced PCOS model. Additionally, the insulin resistance and hepatic lesions seen in the DHEA-induced PCOS model were observed in the MG-BSA treatment group. Taken together, we found that AGEs exert a toxic effect on ovarian granulosa cells, ovarian morphology, and the estrous cycle that mimics the DHEA-induced PCOS phenotypes.

原文英語
文章編號327
期刊Biomolecules
9
發行號8
DOIs
出版狀態已發佈 - 八月 1 2019

指紋

Advanced Glycosylation End Products
Granulosa Cells
Polycystic Ovary Syndrome
Cell proliferation
Progesterone
Dehydroepiandrosterone
Cell Proliferation
Estrous Cycle
LH Receptors
Poisons
Phenotype
Therapeutics
Rats
Tumors
Serum
Cells
Insulin Resistance
Insulin
Cysts
Down-Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

引用此文

Dietary glycotoxins, advanced glycation end products, inhibit cell proliferation and progesterone secretion in ovarian granulosa cells and mimic PCOS-like symptoms. / Lin, Po Han; Chang, Chih Chao; Wu, Kun Hsuan; Shih, Chun Kuang; Chiang, Wenchang; Chen, Hsin Yuan; Shih, Yin Hwa; Wang, Kei Lee; Hong, Yong Han; Shieh, Tzong Ming; Hsia, Shih Min.

於: Biomolecules, 卷 9, 編號 8, 327, 01.08.2019.

研究成果: 雜誌貢獻文章

Lin, Po Han ; Chang, Chih Chao ; Wu, Kun Hsuan ; Shih, Chun Kuang ; Chiang, Wenchang ; Chen, Hsin Yuan ; Shih, Yin Hwa ; Wang, Kei Lee ; Hong, Yong Han ; Shieh, Tzong Ming ; Hsia, Shih Min. / Dietary glycotoxins, advanced glycation end products, inhibit cell proliferation and progesterone secretion in ovarian granulosa cells and mimic PCOS-like symptoms. 於: Biomolecules. 2019 ; 卷 9, 編號 8.
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abstract = "Women with polycystic ovary syndrome (PCOS) have been reported to have an elevated serum advanced glycation end product (AGE) level. However, the effect of AGEs on the pathophysiological ovarian granulosa cells of PCOS is still unclear. In this study, five indented BSA-derived AGE products were used to evaluate their effect on the function of human granulosa cells. We found that the proliferation of both primary human ovarian granulosa (hGC) cells and human granulosa-like tumor (KGN) cells were inhibited by treatment with these five AGE products. The progesterone secretion level was also reduced in both hGC and KGN cells by treatment with these AGE products through downregulation of LH receptor/cAMP regulatory activity. The granulosa cell layer and serum progesterone level were reduced in rats by treatment with MG-BSA; moreover, an increased number of follicle cysts and an irregular estrous cycle were observed. MG-BSA treatment had a similar effect on the phenotypes of the DHEA-induced PCOS model. Additionally, the insulin resistance and hepatic lesions seen in the DHEA-induced PCOS model were observed in the MG-BSA treatment group. Taken together, we found that AGEs exert a toxic effect on ovarian granulosa cells, ovarian morphology, and the estrous cycle that mimics the DHEA-induced PCOS phenotypes.",
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AU - Lin, Po Han

AU - Chang, Chih Chao

AU - Wu, Kun Hsuan

AU - Shih, Chun Kuang

AU - Chiang, Wenchang

AU - Chen, Hsin Yuan

AU - Shih, Yin Hwa

AU - Wang, Kei Lee

AU - Hong, Yong Han

AU - Shieh, Tzong Ming

AU - Hsia, Shih Min

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N2 - Women with polycystic ovary syndrome (PCOS) have been reported to have an elevated serum advanced glycation end product (AGE) level. However, the effect of AGEs on the pathophysiological ovarian granulosa cells of PCOS is still unclear. In this study, five indented BSA-derived AGE products were used to evaluate their effect on the function of human granulosa cells. We found that the proliferation of both primary human ovarian granulosa (hGC) cells and human granulosa-like tumor (KGN) cells were inhibited by treatment with these five AGE products. The progesterone secretion level was also reduced in both hGC and KGN cells by treatment with these AGE products through downregulation of LH receptor/cAMP regulatory activity. The granulosa cell layer and serum progesterone level were reduced in rats by treatment with MG-BSA; moreover, an increased number of follicle cysts and an irregular estrous cycle were observed. MG-BSA treatment had a similar effect on the phenotypes of the DHEA-induced PCOS model. Additionally, the insulin resistance and hepatic lesions seen in the DHEA-induced PCOS model were observed in the MG-BSA treatment group. Taken together, we found that AGEs exert a toxic effect on ovarian granulosa cells, ovarian morphology, and the estrous cycle that mimics the DHEA-induced PCOS phenotypes.

AB - Women with polycystic ovary syndrome (PCOS) have been reported to have an elevated serum advanced glycation end product (AGE) level. However, the effect of AGEs on the pathophysiological ovarian granulosa cells of PCOS is still unclear. In this study, five indented BSA-derived AGE products were used to evaluate their effect on the function of human granulosa cells. We found that the proliferation of both primary human ovarian granulosa (hGC) cells and human granulosa-like tumor (KGN) cells were inhibited by treatment with these five AGE products. The progesterone secretion level was also reduced in both hGC and KGN cells by treatment with these AGE products through downregulation of LH receptor/cAMP regulatory activity. The granulosa cell layer and serum progesterone level were reduced in rats by treatment with MG-BSA; moreover, an increased number of follicle cysts and an irregular estrous cycle were observed. MG-BSA treatment had a similar effect on the phenotypes of the DHEA-induced PCOS model. Additionally, the insulin resistance and hepatic lesions seen in the DHEA-induced PCOS model were observed in the MG-BSA treatment group. Taken together, we found that AGEs exert a toxic effect on ovarian granulosa cells, ovarian morphology, and the estrous cycle that mimics the DHEA-induced PCOS phenotypes.

KW - Advanced glycation end products (AGEs)

KW - Dehydroepiandrosterone (DHEA)

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