Biomarker Profiles in Women with PCOS and PCOS Offspring; A Pilot Study.
OBJECTIVE
To study metabolic/inflammatory biomarker risk profiles in women with PCOS and PCOS offspring.


METHODS
Cross-sectional comparison of serum biomarkers.


METHODS
University Medical Center Utrecht.


METHODS
Hyperandrogenic PCOS women (HA-PCOS, n = 34), normoandrogenic PCOS women (NA-PCOS, n = 34), non-PCOS reference population (n = 32), PCOS offspring (n = 14, age 6-8 years), and a paedriatic reference population (n = 30).


METHODS
Clustering profile of adipocytokines (IL-1b, IL-6, IL-13, IL-17, IL-18, TNF-α, adiponectin, adipsin, leptin, chemerin, resistin, RBP4, DPP-IV/sCD26, CCL2/MCP-1), growth factors (PIGF, VEGF, sVEGF-R1), soluble cell adhesion molecules (sICAM-1/sCD54, sVCAM-1/sCD106), and other inflammatory related proteases (MMP-9, S100A8, Cathepsin S). Differences in median biomarker concentrations between groups, and associations with the free androgen index (FAI; Testosterone/SHBG x100).


RESULTS
The cluster analysis identified leptin, RBP-4, DPP-IV and adiponectin as potential discriminative markers for HA-PCOS with a specifically strong correlation in cases with increased BMI. Leptin (R2 = 0.219) and adiponectin (R2 = 0.182) showed the strongest correlation with the FAI. When comparing median protein concentrations adult PCOS women with or without hyperandrogenemia, the most profound differences were observed for leptin (P < 0.001), DPP-IV (P = 0.005), and adiponectin (P < 0.001). Adjusting for age, BMI and multiple testing attenuated all differences. In PCOS offspring, MMP-9 (P = 0.001) and S100A8 (P < 0.001) concentrations were significantly higher compared to a healthy matched reference population, even after correcting for age and BMI and adjustment for multiple testing.


CONCLUSIONS
In this preliminary investigation we observed significant differences in adipocytokines between women with or without hyperandrogenic PCOS and non-PCOS controls, mostly influenced by BMI. Leptin and adiponectin showed the strongest correlation with the FAI in adult women with PCOS. In PCOS offspring other inflammatory biomarkers (MMP-9, S100A8) were increased, suggesting that these children may exhibit increased chronic low-grade inflammation. Additional research is required to confirm results of the current exploratory investigation.
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
Nadine M P
NM
Daan
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
Maria P H
MP
Koster
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
Marlieke A
MA
de Wilde
Julius Centre for Health Sciences and Primary care, University Medical Center Utrecht, Utrecht, the Netherlands.
Gerdien W
GW
Dalmeijer
Julius Centre for Health Sciences and Primary care, University Medical Center Utrecht, Utrecht, the Netherlands.
Annemieke M V
AM
Evelein
Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Utrecht, the Netherlands.
Bart C J M
BC
Fauser
Laboratory of Translational Immunology, Division of Pediatrics, Wilhelmina Children's Hospital, Utrecht, the Netherlands.
Wilco
W
de Jager
D000328:Adult; D015415:Biomarkers; D002648:Child; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D011085:Polycystic Ovary Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D055815:Young Adult
D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators