Obesity-induced follicular phase endometrial proteome dysregulation in a well-phenotyped population

Emma Giuliani, Samantha B. Schon, Kun Yang, Gregory Willis Burns, Lisa M. Neff, Henriette A. Remmer, Jose M. Teixeira, Erica E. Marsh
In: F&S Science · 2022 · vol. 3(4) , pp. 367–375 · doi:10.1016/j.xfss.2022.06.002 · PMID:35710094 · W4282823810
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This study found that obesity dysregulates the mid-follicular phase endometrial proteome, with 15 proteins underexpressed in obese women, potentially impacting hormonal and immunologic pathways.

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Abstract

OBJECTIVE: ). DESIGN: Clinical cross-sectional study. SETTING: Academic Medical Center. PATIENT(S): Healthy, normally-cycling, 18 to 40-year-old women (n = 6 OW and n = 6 NWW). MAIN OUTCOME MEASURE(S): Participants underwent screening and midfollicular phase visits. Demographic and anthropometric characteristics, blood samples, ultrasounds, and follicular phase endometrial biopsies were collected. Proteomic analyses of endometrial samples (liquid chromatography-mass spectrometry) were performed. Proteins with ≥2-fold difference and a false discovery rate of <0.1 were considered statistically significant (Benjamini-Hochberg adjustment). RESULT(S): Reproductive hormone levels did not differ between the two groups. Mean BMI, serum leptin concentration, and bioelectrical impedance analysis indices of adiposity were higher in OW than in NWW. Histological examination of the endometrial samples confirmed normal-appearing endometrium in both OW and NWW. A total of 2,930 proteins were detected across all samples, with an average number of proteins per sample of 2,059 ± 482 in NWW and 2,437 ± 187 in OW. A total of 17 proteins were differentially expressed in OW vs. NWW; 2 were more abundant, whereas 15 were underexpressed in OW, including the progesterone receptor. CONCLUSION(S): In this well-phenotyped population of healthy women, obesity was associated with significant endometrial proliferative phase proteomic differences affecting the hormonal and immunologic pathways. These could contribute to an increased risk of menstrual bleeding abnormalities and create an altered environment for future luteinization.

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