Objective/Background: While PCOS research has extensively explored genomic, transcriptomic, proteomic, and metabolomic milieus, our study examines the plasma glycome, comparing women with PCOS to age-matched healthy controls. Methods: In this observational study, an n = 47 women with PCOS were screened and enrolled at the UC Davis Health campus, the comparator group constituted an n = 25 age-matched healthy women. During a study visit, body composition was measured using a bioelectrical impedance scale, and fasted plasma samples were obtained to measure glucose, insulin, circulating lipids and leptin, among other parameters, in all groups. In addition, in the PCOS group, circulating androgens and other endocrine hormones were measured. The plasma glycome was measured using a UHPLC-MS protocol.   Results: As expected, women with PCOS had more body weight (p<0.01), body fat (p = 0.004), fasting leptin (p=0.01), insulin (p = 0.003) and glucose (p = 0.004). The plasma glycome milieu displayed increased tetraantennary (glycans with 4 branches: p = 0.05) and reduced hybrid-type glycans (p = 0.019) in women with PCOS compared to healthy controls. Logistic regression models predicting PCOS vs control binary outcomes indicated a higher tetraantennary and lower hybrid glycan profile to represent women with PCOS more than controls both with (AUCROC = 0.94) and without body weight (AUCROC = 0.84). Further, in women with PCOS, total testosterone was positively associated with tetra-antennary glycans (r = 0.322, p = 0.029). Conclusions: Highly branched glycans, that have been shown to be elevated in pro-inflammatory and metabolic disease states, are also elevated in PCOS. However, the link between circulating androgens and protein glycosylation in women remains unknown, and future investigations should focus on this.

The authors have declared no competing interest.

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The author(s) received no specific funding for this work.

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The UC Davis Institutional Review Board approved the study, and all participants signed written informed consent forms.

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All data will be made available on our github page upon manuscript acceptance - https://github.com/Glyconutlab.

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