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Recent updates on animal models for understanding the etiopathogenesis of polycystic ovarian syndrome

Corrie L, Gulati M, Singh SK, Kapoor B, Khursheed R, Awasthi A, et al.

Life Sci, 2021 Sep 01;280:119753.
PMID: 34171379 DOI: 10.1016/j.lfs.2021.119753

Polycystic ovarian syndrome (PCOS) is the primary cause of female infertility affecting several women worldwide. Changes in hormonal functions such as hyperandrogenism are considered a significant factor in developing PCOS in women. In addition, many molecular pathways are involved in the pathogenesis of PCOS in women. To have better insights about PCOS, it is data from clinical studies carried on women suffering from PCOS should be collected. However, this approach has several implications, including ethical considerations, cost involved and availability of subject. Moreover, during the early drug development process, it is always advisable to use non-human models mimicking human physiology as they are less expensive, readily available, have a shorter gestation period and less risk involved. Many animal models have been reported that resemble the PCOS pathways in human subjects. However, the models developed on rats and mice are more preferred over other rodent/non-rodent models due to their closer resemblance with human PCOS development mechanism. The most extensively reported PCOS models for rats and mice include those induced by using testosterone, letrozole and estradiol valerate. As the pathophysiology of PCOS is complex, none of the explored models completely surrogates the PCOS related conditions occurring in women. Hence, there is a need to develop an animal model that can resemble the pathophysiology of PCOS in women. The review focuses on various animal models explored to understand the pathophysiology of PCOS. The article also highlights some environmental and food-related models that have been used to induce PCOS.

Matched MeSH terms: Polycystic Ovary Syndrome/pathology*
Fulltext Evaluation of clinical manifestations, health risks, and quality of life among women with polycystic ovary syndrome

Sidra S, Tariq MH, Farrukh MJ, Mohsin M

PLoS One, 2019;14(10):e0223329.
PMID: 31603907 DOI: 10.1371/journal.pone.0223329

This study aimed to evaluate the clinical manifestations and health risks associated with polycystic ovary syndrome (PCOS) and its impact on quality of life (QOL) in Pakistan. A detailed cross-sectional study was conducted on PCOS among women of reproductive age visiting the gynecology and obstetrics and endocrinology departments at primary and tertiary care hospitals located in Abbottabad, Kohat, and Islamabad. In total, 440 patients meeting the inclusion criteria were included. A checklist was specifically designed to identify symptoms and health risks, including adverse drug reactions, complications, irrational prescription or underprescription, and drug-drug interactions. The Short Form-12 questionnaire was used to evaluate the QOL of patients with PCOS. Data collected were analyzed for descriptive and inferential statistics using chi-square test, analysis of variance, and post hoc analysis. All patients exhibited the cardinal symptoms of PCOS, including obesity (n = 352, 80%), acne (n = 296, 67.3), hirsutism (n = 299, 68%), hyperglycemia (n = 278, 63.2%), and irregular menstruation (n = 316, 71.8%). Ultrasonography confirmed that 268 (61%) patients had multiple cysts of >10 mm in diameter. Patients with untreated PCOS exhibited a high prevalence of health risks including hypertension (n = 87, 19.8%), diabetes (n = 268, 60.9%), sleep apnea (n = 11, 2.5%), infertility (n = 146, 33.2%), increased endometrial thickness (n = 21, 4.8%), miscarriages (n = 68, 15.5%), high cholesterol level (n = 85, 19.3%), and hyperandrogenism (n = 342, 77.7%). Most patients exhibited low QOL scores (n = 374, 85%), with depression being the largest contributor to low QOL. Apart from novel results, this study found an association between depression and low QOL in patients with PCOS, suggesting the need for reviewing the management guidelines and psychological health assessment of women with PCOS.

Matched MeSH terms: Polycystic Ovary Syndrome/pathology*
Fulltext Ficus deltoidea ameliorates biochemical, hormonal, and histomorphometric changes in letrozole-induced polycystic ovarian syndrome rats

Haslan MA, Samsulrizal N, Hashim N, Zin NSNM, Shirazi FH, Goh YM

BMC Complement Med Ther, 2021 Nov 29;21(1):291.
PMID: 34844580 DOI: 10.1186/s12906-021-03452-6

BACKGROUND: Insulin resistance and hormonal imbalances are key features in the pathophysiology of polycystic ovarian syndrome (PCOS). We have previously shown that Ficus deltoidea var. deltoidea Jack (Moraceae) can improve insulin sensitivity and hormonal profile in PCOS female rats. However, biological characteristics underpinning the therapeutic effects of F. deltoidea for treating PCOS remain to be clarified. This study aims to investigate the biochemical, hormonal, and histomorphometric changes in letrozole (LTZ)-induced PCOS female rats following treatment with F. deltoidea.
METHODS: PCOS was induced in rats except for normal control by administering LTZ at 1 mg/kg/day for 21 days. Methanolic extract of F. deltoidea leaf was then orally administered to the PCOS rats at the dose of 250, 500, or 1000 mg/kg/day, respectively for 15 consecutive days. Lipid profile was measured enzymatically in serum. The circulating concentrations of reproductive hormone and antioxidant enzymes were determined by ELISA assays. Ovarian and uterus histomorphometric changes were further observed by hematoxylin and eosin (H&E) staining.
RESULTS: The results showed that treatment with F. deltoidea at the dose of 500 and 1000 mg/kg/day reduced insulin resistance, obesity indices, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL), malondialdehyde (MDA), testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) to near-normal levels in PCOS rats. The levels of high-density lipoprotein cholesterol (HDL), estrogen, and superoxide dismutase (SOD) are also similar to those observed in normal control rats. Histomorphometric measurements confirmed that F. deltoidea increased the corpus luteum number and the endometrial thickness.
CONCLUSIONS: F. deltoidea can reverse PCOS symptoms in female rats by improving insulin sensitivity, antioxidant activities, hormonal imbalance, and histological changes. These findings suggest the potential use of F. deltoidea as an adjuvant agent in the treatment program of PCOS.

Matched MeSH terms: Polycystic Ovary Syndrome/pathology
The effect of Metformin on endometrial tumor-regulatory genes and systemic metabolic parameters in polycystic ovarian syndrome--a proof-of-concept study

Shafiee MN, Malik DA, Yunos RI, Atiomo W, Omar MH, Ghani NA, et al.

Gynecol Endocrinol, 2015 Apr;31(4):286-90.
PMID: 25495168 DOI: 10.3109/09513590.2014.989982

The aim of this proof-of-concept study was to determine the effects of three-month Metformin therapy on the expression of tumor-regulatory genes (p53, cyclin D2 and BCL-2) in the endometrium of women with polycystic ovary syndrome (PCOS). A total of 40 women, aged between 21 and 45 years with PCOS (Rotterdam criteria) were recruited. The participants were assessed at pre- and 3-month-post-Metformin therapy for the menstrual regularities, weight reduction, Ferriman Galway scores, fasting blood glucose (FBG), total cholesterol, LDL, HDL and p53, BCL-2 and cyclin D2 gene expression. Five participants conceived spontaneously after the initial recruitment. Majority (68%) resumed regular menstrual cycles after Metformin. There were significant reduction in BMI (p = 0.001), weight (p = 0.001) and Ferriman Galway scores (p = 0.001). A significant improvement was seen in mean FBG (p = 0.002), total cholesterol (p = 0.001), LDL (p = 0.003) and HDL cholesterol levels (p = 0.015). Tumor suppressor gene (p53) was significantly up-regulated after Metformin (10 out of 14 women), with p value 0.016. BCL-2 and cyclin D2 (oncogenes) were slightly up-regulated without significant difference (p = 0.119 and 0.155, respectively). In conclusion, Metformin therapy improved clinical and metabolic parameters in women with PCOS and up-regulated p53 tumor suppressor gene significantly. Further studies are however required to independently validate our findings.

Matched MeSH terms: Polycystic Ovary Syndrome/pathology