The Lifestyle Modifications and Endometrial Proteome Changes of Women With Polycystic Ovary Syndrome and Obesity

Abstract

Polycystic ovary syndrome (PCOS) is a polyendocrine disorder and the most common endocrinopathy in women of reproductive age. Affected women have an elevated prevalence of being overweight and obese. Our study sought to determine how weight loss associated with lifestyle changes affects the endometrium specific proteome, endocrine-metabolic characteristics, and motor capabilities of obese women with PCOS and infertility. A group of 12 infertile women under the age of 38 with PCOS and BMI ≥30 kg/m² were included in the study. An evaluation was performed by a gynecologist and an endocrinologist. The weight-loss program lasted 8 weeks under the guidance of a professional trainer. Endometrial sampling during a period of implantation window for proteome determination was performed before and after weight loss. In endometrial samples at the end of the study increased protein abundance was recorded for Legumain, Insulin-like growth factor-binding protein 7, Hepatocyte growth factor receptor, Keratin, type II cytoskeletal 7, and Cystatin-B, while the B-lymphocyte antigen CD20 protein abundance decreased. Our results also indicate significantly lowered fasting blood glucose level and free testosterone concentration and significant improvements in body composition and physical capacity. This study may open up the venues for investigating important biomarkers that may affect endometrial receptivity.

Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04989244?term=NCT04989244&draw=2&rank=1, identifier: NCT04989244.

Keywords: PCOS (polycystic ovary syndrome); endometrium; glucose; infertility; obesity; proteome; testosterone; weight loss.

Figure 1

The flow chart of patient recruitment.

Figure 2

Several proteins exhibited distinct abundance variations in END samples (final visit) and START samples (baseline visit). The volcano plot visualizes the p-values (adjusted for multiple testing) and corresponding log-fold changes (logFC). A significance level of adj. p-value = 0.05 is indicated as a horizontal red line. The logFC cutoffs are indicated as vertical lines. Proteins with a positive logFC had a higher abundance in END samples, proteins with a negative value in START samples.

Figure 3

Individual array values for a set of differential proteins. Each sample is measured by four replicate spots per array.

Figure 4

Functional associations of the studied proteins. The colored nodes signify a direct interaction with other proteins. The confidence cutoff for showing interaction links has been set to “high” (0.700) for CD20 and ‘highest’ (0.900) for Legumain, IGFBP-7, HGF receptor, CK-7, and Cystatin-B. (A) Legumain (LGMN), (B) IGFBP-7 (IGFBP7), (C) HGF receptor (MET), (D) CK-7 (KRT7), (E) Cystatin-B (CSTB), (F) CD20 (MS4A1). All abbreviations in figure 4 are explained in the Supplementary File S2 .

Figure 5

Protein-protein interaction between all investigated proteins. The green line represents the simultaneous mention of related proteins in the published literature. The pink line represents that putative homologs were found interacting in other organisms. The black line represents coexpression of proteins in human or coexpression of their putative homologs in other organisms. Coexpression predicts functional association between the proteins. In our network, there is coexpression between HGF receptor and Legumain and between HGF receptor and CK-7, suggesting their likely significant functional interaction. Legumain (LGMN), IGFBP-7 (IGFBP7), HGF receptor (MET), CK-7 (KRT7), Cystatin-B (CSTB), CD20 (MS4A1).