These findings provide evidence for the significant influence of body composition on oocyte transcript abundance in women undergoing hormonal induction to retrieve oocytes. They further identify the potential for maternal diet to influence oocyte gene expression. The preconception period is, therefore, an important window of opportunity to consider for lifestyle interventions.
The effect of glucose in a modified Ham's F10 medium (MM) without hypoxanthine, phosphate and transition metals on human fertilization and sperm survival in vitro was determined. Mature human oocytes from in-vitro fertilization (IVF) patients or Percoll-washed human spermatozoa were randomly allocated to one of the treatment groups: normal Ham's F10, MM, MM with 5 mM glucose (HGMM) and MM with 0.5 mM glucose (LGMM). Oocytes were inseminated in one of the four media for 12-20 h and checked for fertilization. Sperm were incubated likewise for 4 and 24 h, and sperm motility and sperm movement characteristics including average path velocity (VAP), curvilinear velocity (VCL), straight line velocity (VSL), amplitude of lateral head displacement (ALH), beat cross frequency (BCF), straightness (STR), and linearity (LIN) were determined using computer-assisted semen analysis. Fertilization rates were significantly lower in oocytes cultured in MM (23.8%) compared to LGMM (75.5%), HGMM (73.6%) or Ham's F10 (71.1%). Sperm characteristics after 4 h incubation in all four media were similar, except VAP, VSL, VCL and ALH were significantly lower in MM (no glucose) in comparison with the other three media. After 24 h VAP, VSL, VCL, ALH, LIN and percentage rapid spermatozoa were significantly higher in spermatozoa incubated in HGMM or Ham's F10 compared with MM or LGMM. Also after 24 h, the percentage of spermatozoa which were highly motile was greater in HGMM than in Ham's F10. Absence of glucose significantly lowered fertilization rates and sperm movement characteristics in vitro.
Although obesity negatively influences the metabolic homeostasis of cells within a broad range of tissues, its impact on oocyte metabolism is not fully understood. Prior evidence suggests that obesity increases expression of oocyte genes associated with inflammation, oxidative stress, and lipid metabolism; however, the metabolic impact of these genetic differences is not known. To address this gap, we conducted an exploratory assessment of the follicular fluid (FF) metabolome in eight overweight/obese (OW) and nine normal-weight (NW) women undergoing in vitro fertilization. FF and serum were collected and analyzed by untargeted metabolomics using gas chromatography-quadrupole time-of-flight mass spectrometry and charged-surface hybrid column-electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Untargeted metabolomics identified obesity-associated changes in FF metabolites related to oxidative stress/antioxidant capacity, xenometabolism/amino acid biosynthesis, and lipid metabolism. Discriminant FF metabolites included elevated uric acid, isothreonic acid, one unknown primary metabolite, and six unknown complex lipids in OW compared with NW women. Conversely, 2-ketoglucose dimethylacetal, aminomalonate, two unknown primary metabolites, and two unknown complex lipids were decreased in FF of OW relative to NW women. Indole-3-propionic acid (IPA), a bacteria-derived metabolite, was also decreased in both FF and serum of OW women ( P < 0.05). The significant correlation between antioxidant IPA in serum and FF ( R = 0.95, P < 0.0001) suggests a potential serum biomarker of FF antioxidant status or reflection of the gut metabolism interaction with the follicle. These results suggest that obesity has important consequences for the follicular environment during the preconception period, a window of time that may be important for lifestyle interventions to ameliorate obesity-associated risk factors.
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