Overexpressed kisspeptin/Kiss1R system in human granulosa cells may be involved in the pathogenesis of polycystic ovary syndrome (PCOS) by inhibiting ovulation

2018 ◽  
Author(s):  
Kai-Lun Hu ◽  
Yang Yu
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Human Granulosa Cells

Association between BMI and gene expression of anti-Müllerian hormone and androgen receptor in human granulosa cells in women with and without polycystic ovary syndrome

2016 ◽  
Vol 85 (4) ◽  
pp. 590-595 ◽  
Author(s):  
Mohammad Nouri ◽  
Esmat Aghadavod ◽  
Sajad Khani ◽  
Mehri Jamilian ◽  
Mehrnush Amiri Siavashani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Androgen Receptor ◽  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Human Granulosa Cells

scholarly journals Metformin Inhibits Aromatase via an Extracellular Signal-Regulated Kinase-Mediated Pathway

Endocrinology ◽  
2009 ◽  
Vol 150 (10) ◽  
pp. 4794-4801 ◽  
Author(s):  
Suman Rice ◽  
Laura Pellatt ◽  
Kumaran Ramanathan ◽  
Saffron Anne Whitehead ◽  
Helen Diane Mason
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Granulosa Cells ◽  
Insulin Treatment ◽  
Polycystic Ovary ◽  
Aromatase Activity ◽  
Erk Pathway ◽  
Ovary Syndrome ◽  
Human Granulosa Cells ◽  
Aromatase Mrna

Abstract Metformin treatment, now widely prescribed in polycystic ovary syndrome, is aimed at correcting the associated insulin resistance, but it has also been shown to directly inhibit ovarian steroidogenesis. The mechanisms, however, by which metformin inhibits estradiol production in human granulosa cells remains unknown. Granulosa luteal cells were incubted with metformin, insulin, or combined metformin and insulin treatment, and aromatase mRNA expression was quantified using real-time RT-PCR. Enzyme activity was assessed by the conversion of 3H-androstenedione to estrone and estradiol. Metformin’s effect on the expression of specific untranslated first exon aromatase promoters was analyzed using semiquantitative PCR. The involvement of MAPK kinase (MEK)/ERK pathway was investigated by immunoblotting for aromatase, phosphorylated, and total ERK-1,2 from cells cultured as above with/without the MEK inhibitor PD98059. Metformin significantly inhibited basal and insulin-stimulated aromatase mRNA expression, with parallel results from the aromatase activity assay and protein assessment. This suppression was via down-regulation of aromatase promoter II, I.3, and 1.4 expression and was reversed by the addition of PD98059. Involvement of the ERK signaling pathway was demonstrated by the significant increase in phosphorylated ERK-1,2 with the combined metformin and insulin treatment. We have shown for the first time in human granulosa cells that metformin signficantly attenuated basal and insulin-stimulated P450 aromatase mRNA expression and activity, via silencing of key promoters. This occurred by activation of MEK/ERK pathway, which negatively regulated aromatase production. This is an important consideration given metformin’s widespread use in polycystic ovary syndrome and may further support a possible therapeutic indication in estrogen-dependent breast tumors.

scholarly journals The effects of di(2-ethylhexyl) phthalate exposure in women with polycystic ovary syndrome undergoing in vitro fertilization

2019 ◽  
Vol 47 (12) ◽  
pp. 6278-6293 ◽  
Author(s):  
Yue Jin ◽  
Qing Zhang ◽  
Jie-Xue Pan ◽  
Fang-Fang Wang ◽  
Fan Qu
Keyword(s):  
In Vitro Fertilization ◽  
Polycystic Ovary Syndrome ◽  
Granulosa Cells ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Vitro Fertilization ◽  
Human Granulosa Cells ◽  
Ethylhexyl Phthalate ◽  
Dehp Exposure

Objectives Di(2-ethylhexyl) phthalate (DEHP) is a common endocrine-disrupting chemical, which has potential reproductive toxicity. This study aimed to explore the effects of DEHP exposure in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization. Methods In this case-control study, DEHP levels in follicular fluid (FF) of women with PCOS (n = 56) and controls (n = 51) were measured. The in vitro effects of DEHP exposure on primary-cultured human granulosa cells (GCs) and a steroidogenic human granulosa-like tumor cell line (KGN cells) were analyzed. Results Concentrations of DEHP in FF were significantly higher in women with PCOS than in controls. The clinical pregnancy rate was significantly lower in women with PCOS with high levels of DEHP than in controls. The levels of androgens produced by human GCs were significantly increased following DEHP exposure. Compared with controls, DEHP-treated human GCs and KGN cells showed significantly lower viability, cell cycle arrest, higher apoptosis, and altered expression of apoptosis-related genes. Conclusion Women with PCOS are exposed to increased levels of DEHP in follicles, which may be associated with pregnancy loss following in vitro fertilization. DEHP may disrupt steroid production, balance in cellular proliferation, and apoptosis in human granulosa cells.

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