Dataset Information

The insulin signaling pathway is dysregulated in cumulus cells from obese, infertile women with polycystic ovarian syndrome with an absence of clinical insulin resistance.

ABSTRACT:

Methods

This is a cohort study, conducted at a university-based reproductive medicine center and private reproductive medicine center that aimed to evaluate granulosa cumulus cell gene expression in the insulin signaling pathway in Polycystic Ovary Syndrome (PCOS) patients undergoing in vitro fertilization (IVF) treatment and to compare the cumulus gene expression between normal weight and obese women without clinical insulin resistance. Fifteen PCOS patients, nine normal weight patients and six obese patients presenting normal HOMA IR (Homeostasis Model Assessment-Insulin Resistance), participated. Patients underwent oocyte retrieval for IVF and after the procedure, granulosa cumulus cells were removed from the oocytes for RNA extraction. Quantitative polymerase chain reaction (PCR) array analysis of 84 genes from insulin signaling pathway was conducted. The results were expressed as fold up- or fold down-expression in obese patients compared with normal weight patients. Any fold change ?3 or ?3 and any p???0.05 were considered statistically significant.

Results

There were 10 genes that were overexpressed in obese compared with normal weight women, BCL2L1, BRAF, CBL, DOK1, FBP1, FRS2, MTOR, PCK2, RPS6KA1, and SORBS1, that had a fold change ?3 and p???0.05.

Discussion

In the obese group, the overexpressed genes are mainly responsible for the proliferation and differentiation of cumulus cells during oocyte maturation, insulin resistance, apoptosis regulation, and glucose metabolism during early embryogenesis, suggesting that in the follicular environment, insulin resistance is present even in the absence of clinical signs.

Conclusion

Together, our findings and the related literature suggest that those alterations may be associated with the worse prognosis of follicular development and oocyte maturation observed in PCOS obese women.

SUBMITTER: Chehin MB

PROVIDER: S-EPMC7303777 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Publications

The insulin signaling pathway is dysregulated in cumulus cells from obese, infertile women with polycystic ovarian syndrome with an absence of clinical insulin resistance.

Chehin Mauricio B MB Fraietta Renato R Lorenzon Aline R AR Bonetti Tatiana C S TCS Motta Eduardo L A ELA

Therapeutic advances in reproductive health 20200101

<h4>Methods</h4>This is a cohort study, conducted at a university-based reproductive medicine center and private reproductive medicine center that aimed to evaluate granulosa cumulus cell gene expression in the insulin signaling pathway in Polycystic Ovary Syndrome (PCOS) patients undergoing in vitro fertilization (IVF) treatment and to compare the cumulus gene expression between normal weight and obese women without clinical insulin resistance. Fifteen PCOS patients, nine normal weight patients ...[more]

PMID: 32596667

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Project description:Lifestyle modification is recommended in women with polycystic ovary syndrome (PCOS) prior to conception but there are few randomized trials to support its implementation or benefit.This study aimed to determine the relative efficacy of preconception intervention on reproductive and metabolic abnormalities in overweight/obese women with PCOS.This was a randomized controlled trial of preconception and infertility treatment at Academic Health Centers in women with infertility due to PCOS, age 18-40 y and body mass index 27-42 kg/m(2).Women were randomly assigned to receive either 16 weeks of 1) continuous oral contraceptive pills (OCPs) (ethinyl estradiol 20 mcg/1 mg norethindrone acetate) ("OCP"); 2) lifestyle modification consisting of caloric restriction with meal replacements, weight loss medication (either sibutramine, or orlistat), and increased physical activity to promote a 7% weight loss ("Lifestyle"); or 3) combined treatment with both OCP and lifestyle modification ("Combined"). After preconception intervention, women underwent standardized ovulation induction with clomiphene citrate and timed intercourse for four cycles. Pregnancies were followed with trimester visits until delivery.Weight, ovulation, and live birth were measured.We consented 216 and randomly assigned 149 women (Lifestyle: n = 50; OCP: n = 49; Combined: n = 50). We achieved significant weight loss with both Lifestyle (mean weight loss, -6.2%; 95% confidence interval (CI), -7.4--5.0; and Combined (mean weight loss, -6.4%; 95% CI, -7.6--5.2) compared with baseline and OCP (both P < .001). There was a significant increase in the prevalence of metabolic syndrome at the end of preconception treatment compared with baseline within OCP (odds ratio [OR, 2.47; 95% CI, 1.42-4.27) whereas no change in metabolic syndrome was detected in the Lifestyle (OR, 1.18; 95% CI, 0.63-2.19) or Combined (OR, 0.72; 95% CI, 0.44-1.17) groups. Cumulative ovulation rates were superior after weight loss: OCP, 46%; Lifestyle, 60%; and Combined, 67% (P < .05). Live birth rates were OCP, 12%; Lifestyle, 26%; and Combined, 24% (P = .13).A preconception weight loss intervention eliminates the adverse metabolic oral contraceptive effects and, compared with oral contraceptive pretreatment, leads to higher ovulation rates.

Project description:ContextObesity is associated with insulin-resistance (IR), the key feature of type 2 diabetes. Although chronic low-grade inflammation has been identified as a central effector of IR development, it has never been investigated simultaneously at systemic level and locally in skeletal muscle and adipose tissue in obese humans characterized for their insulin sensitivity.ObjectivesWe compared metabolic parameters and inflammation at systemic and tissue levels in normal-weight and obese subjects with different insulin sensitivity to better understand the mechanisms involved in IR development.Methods30 post-menopausal women were classified as normal-weight insulin-sensitive (controls, CT) and obese (grade I) insulin-sensitive (OIS) or insulin-resistant (OIR) according to their body mass index and homeostasis model assessment of IR index. They underwent a hyperinsulinemic-euglycemic clamp, blood sampling, skeletal muscle and subcutaneous adipose tissue biopsies, an activity questionnaire and a self-administrated dietary recall. We analyzed insulin sensitivity, inflammation and IR-related parameters at the systemic level. In tissues, insulin response was assessed by P-Akt/Akt expression and inflammation by macrophage infiltration as well as cytokines and IκBα expression.ResultsSystemic levels of lipids, adipokines, inflammatory cytokines, and lipopolysaccharides were equivalent between OIS and OIR subjects. In subcutaneous adipose tissue, the number of anti-inflammatory macrophages was higher in OIR than in CT and OIS and was associated with higher IL-6 level. Insulin induced Akt phosphorylation to the same extent in CT, OIS and OIR. In skeletal muscle, we could not detect any inflammation even though IκBα expression was lower in OIR compared to CT. However, while P-Akt/Akt level increased following insulin stimulation in CT and OIS, it remained unchanged in OIR.ConclusionOur results show that systemic IR occurs without any change in systemic and tissues inflammation. We identified a muscle defect in insulin response as an early mechanism of IR development in grade I obese post-menopausal women.

Dataset Information

The insulin signaling pathway is dysregulated in cumulus cells from obese, infertile women with polycystic ovarian syndrome with an absence of clinical insulin resistance.

Methods

Results

Discussion

Conclusion

Publications

The insulin signaling pathway is dysregulated in cumulus cells from obese, infertile women with polycystic ovarian syndrome with an absence of clinical insulin resistance.

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