Animal Models for Human Polycystic Ovary Syndrome (PCOS) Focused on the Use of Indirect Hormonal Perturbations: A Review of the Literature

Ryu, Youngjae; Kim, Sung Woo; Kim, Yoon Young; Ku, Seung‐Yup

doi:10.3390/ijms20112720

Cited by 60 publications

(44 citation statements)

References 176 publications

(178 reference statements)

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“…c. In theca-interstitial cells, Pten deletion produced features of PCOS including hyperandrogenism and early fertility loss (154). Animal models suggest that the PI3K/AKT pathway plays a significant role in the molecular pathology of PCOS (155); the outcome of Pten deletion in theca cells is consistent with this. The involvement of PI3K pathway in PCOS is further demonstrated by the fact that PTEN expression is altered in endometrium of PCOS patients (156).…”

Section: Pten and Pcosmentioning

confidence: 81%

PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

Venniyoor

2020

Front. Nutr.

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The modern obesity epidemic with associated disorders of metabolism and cancer has been attributed to the presence of "thrifty genes". In the distant past, these genes helped the organism to improve energy efficiency and store excess energy safely as fat to survive periods of famine, but in the present day obesogenic environment, have turned detrimental. I propose PTEN as the likely gene as it has functions that span metabolism, cancer and reproduction, all of which are deranged in obesity and insulin resistance. The activity of PTEN can be calibrated in utero by availability of nutrients by the methylation arm of the epigenetic pathway. Deficiency of protein and choline has been shown to upregulate DNA methyltransferases (DNMT), especially 1 and 3a; these can then methylate promoter region of PTEN and suppress its expression. Thus, the gene is tuned like a metabolic rheostat proportional to the availability of specific nutrients, and the resultant "dose" of the protein, which sits astride and negatively regulates the insulin-PI3K/AKT/mTOR pathway, decides energy usage and proliferation. This "fixes" the metabolic capacity of the organism periconceptionally to a specific postnatal level of nutrition, but when faced with a discordant environment, leads to obesity related diseases.

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Section: Pten and Pcosmentioning

confidence: 81%

PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

Venniyoor

2020

Front. Nutr.

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“…Using the method of insulin resistance combined with hormonal disorders [ 29 ], we firstly replicated a PCOS mouse model [ 30 ], where we then showed that the health care effect of catechins extract on PCOS was related to the anti-inflammatory and anti-matrix degradation effects in the mouse uterus. Importantly, we demonstrated that the continuing healthcare benefit of catechins extract was to rescue hormonal disorders, insulin resistance, and ovarian and uterine pathological changes of PCOS mice by inhibiting STAT3 signaling in the uterus.…”

Section: Discussionmentioning

confidence: 99%

Catechins from oolong tea improve uterine defects by inhibiting STAT3 signaling in polycystic ovary syndrome mice

Hong

et al. 2020

Chin Med

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Background It is showed that inflammation is causative factor for PCOS, leading to a decline in ovarian fertility. Previous studies have reported that tea consumption can reduce the incidence of ovarian cancer. We speculate that catechins from oolong tea (Camellia sinensis (L.) O. Kuntze) may have a potential therapeutic effect on PCOS. This study aims to investigate the effects of oolong tea catechins on the uterus of polycystic ovary syndrome (PCOS) mice induced by insulin combined with human chorionic gonadotropin (hCG). Methods Sixty female mice were divided into 6 groups (n = 10): model, model + Metformin 200 mg/kg, model + catechins 25 mg/kg, model + catechins 50 mg/kg, and model + catechins 100 mg/kg. Another forty female mice were divided into 4 groups (n = 10): control, control + catechins 100 mg/kg, model, and model + catechins 100 mg/kg. Ovarian and uterine weight coefficients, sex hormone levels, glucose metabolism and insulin resistance, and ovarian and uterine pathology were examined. Changes in NF-κB-mediated inflammation, MMP2 and MMP9 expressions, and STAT3 signaling were evaluated in the uterus of mice. Results Catechins could effectively reduce the ovarian and uterine organ coefficients, reduce the levels of E2, FSH and LH in the blood and the ratio of LH/FSH, and improve glucose metabolism and insulin resistance in PCOS mice induced by insulin combined with hCG. In addition, catechins could significantly down-regulated the expression of p-NF-κB p65 in the uterus and the protein expressions of the pro-inflammatory factors (IL-1β, IL-6, and TNF-α). The expressions of mmp2 and mmp9 associated with matrix degradation in uterine tissue were also significantly down-regulated by catechins. Further, catechins significantly reduced the expression of p-STAT3 and increased the expression of p-IRS1 and p-PI3K in the uterus of PCOS mice. Conclusion Catechins from oolong tea can alleviate ovarian dysfunction and insulin resistance in PCOS mice by inhibiting uterine inflammation and matrix degradation via inhibiting p-STAT3 signaling.

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“…Some genetically engineered or inherited animal models have shown symptoms of PCOS, which are due to inappropriate hormone exposure or ER changes affecting endocrine homeostasis, leading to the development of ovarian abnormalities and a reduction in fertility [ 46 , 47 ]. Paying attention to animal PCOS models is helpful in order for us to better understand the disease characteristics of PCOS (as shown in Table 1 ).…”

Section: Physiological and Pathological Function Of Ersmentioning

confidence: 99%

Estrogen Receptors in Polycystic Ovary Syndrome

Deng

Lian

et al. 2021

Cells

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Female infertility is mainly caused by ovulation disorders, which affect female reproduction and pregnancy worldwide, with polycystic ovary syndrome (PCOS) being the most prevalent of these. PCOS is a frequent endocrine disease that is associated with abnormal function of the female sex hormone estrogen and estrogen receptors (ERs). Estrogens mediate genomic effects through ERα and ERβ in target tissues. The G-protein-coupled estrogen receptor (GPER) has recently been described as mediating the non-genomic signaling of estrogen. Changes in estrogen receptor signaling pathways affect cellular activities, such as ovulation; cell cycle phase; and cell proliferation, migration, and invasion. Over the years, some selective estrogen receptor modulators (SERMs) have made substantial strides in clinical applications for subfertility with PCOS, such as tamoxifen and clomiphene, however the role of ER in PCOS still needs to be understood. This article focuses on the recent progress in PCOS caused by the abnormal expression of estrogen and ERs in the ovaries and uterus, and the clinical application of related targeted small-molecule drugs.

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Animal Models for Human Polycystic Ovary Syndrome (PCOS) Focused on the Use of Indirect Hormonal Perturbations: A Review of the Literature

Cited by 60 publications

References 176 publications

PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

PTEN: A Thrifty Gene That Causes Disease in Times of Plenty?

Catechins from oolong tea improve uterine defects by inhibiting STAT3 signaling in polycystic ovary syndrome mice

Estrogen Receptors in Polycystic Ovary Syndrome

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