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Untargeted Metabolomics Reveal Disparate Metabolite Profile in Follicular Fluid between Obese and Normal Weight Women
Author(s) -
Ruebel Meghan L,
Piccolo Brian D,
Moutos Dean M,
Shankar Kartik,
Andres Aline
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.457.2
Subject(s) - follicular fluid , metabolite , endocrinology , medicine , oocyte , follicular phase , metabolome , chemistry , leptin , obesity , biology , andrology , embryo , microbiology and biotechnology
The microenvironment of follicular fluid is thought to provide a rich source of nutrients and other factors that promotes oocyte growth and viability; however, it is not known if obesity or related sequelae impacts this environment. To address this research gap, we designed a clinical study to assess follicular fluid metabolite profiles, inflammatory markers and oocyte gene expression. Normal weight women (NW; n=13) and overweight/obese (OW; n=11) undergoing fertility treatments were recruited prior to an oocyte retrieval procedure. Anthropometrics, body composition (Air Displacement Plethysmography), and overnight fasting serum samples were collected. During the oocyte retrieval procedures, follicular fluid aspirates containing the oocyte samples were also collected. Leptin, C‐reactive protein, triglycerides, and total cholesterol were assessed in serum and follicular fluid using colorimetric and ELISA assays. Gas chromatography time of flight‐mass spectrometry was used to characterize the metabolome of serum and follicular fluid. Discriminant metabolites of NW and OW samples were identified using a backwards iterative selection strategy using ranked variable importance in projection measurements from partial least squared‐discriminant analysis (PLS‐DA) models. By design, OW women had significantly higher BMI, fat mass, and serum HOMA‐IR compared to NW women ( p<0.01 ). Leptin and C‐reactive protein concentrations were increased in both serum (5.3±1.0 vs. 27.2±6.6 and 3.2±0.7 vs. 5.7±1.0, respectively) and follicular fluid (11.1±2.4 vs. 26.8±6.7 and 2.7±0.8 vs. 5.9±1.8, respectively) from OW women and follicular fluid triglyceride (25.8±14 vs. 64.2±46.9, respectively) and total cholesterol (21.1±3.2 vs. 36.3±7.6, respectively) levels were elevated in OW women compared to NW ( p<0.05 ) women. Metabolites selected as discriminant of NW and OW follicular fluid samples by PLS‐DA included elevated uric acid, isothreonic acid, 2‐deoxytetronic acid and 4 unknown metabolites in OW women. Conversely, 2‐dimethylacetal‐ketoglucose, aminomalonate, and 2 unknown metabolites were significantly decreased in OW relative to NW women. Other serum metabolites discriminant of NW and OW serum included cholesterol, mannose, palmitic acid, sucrose, and 5 unknown metabolites. These results suggest that the follicular fluid metabolome differs between NW and OW women and may potentially contribute to altered oocyte metabolism and development. One unknown metabolite, BB112556, was significantly lower in both follicular fluid and serum, raising the possibility of a serum biomarker of oocyte health and development. Combined with previous findings of differential oocyte gene expression in NW vs. OW women from this cohort, these results suggest that obesity significantly affects oocyte transcription and follicular fluid metabolites. Support or Funding Information ACHRI CUMG 035716 and USDA□ARS Project 6026□51000□010□05S