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Abstract
ObjectiveTo investigate follicular fluid (FF) phthalate levels in adolescents undergoing fertility preservation compared to oocyte donors and explore its association with ovarian reserve and cumulus cell gene expression. DesignRetrospective study, and molecular analysis of cumulus cells (CCs) and FF SubjectsAdolescents (n= 20, 16.7 ± 0.6 years old) undergoing fertility preservation and oocyte donors (n= 24, 26.2 ± 0.4 years old). Main Outcome MeasuresPatient demographics, ovarian stimulation, and oocyte retrieval outcomes were analyzed for each group. FF levels of 9 phthalate metabolites were assessed individually and as molar sums representative of common compounds (all phthalates: ƩPhthalates; di(2-ethylhexyl) phthalate (DEHP) associated phthalate metabolites: ƩDEHP), exposure sources (plastics: ƩPlastic; personal care products: ƩPCP), and modes of action (anti-androgenic: ƩAA) and compared between the two groups. The transcriptome of CC associated with mature oocytes was compared between adolescents and oocyte donors using bulk RNA-sequencing. ResultsFollicular fluid ƩPlastic and ƩPCP levels were significantly higher in adolescents compared to oocyte donors (p<0.05). Follicular fluid ƩDEHP, ƩPlastic, ƩPCP, ƩAA, and ƩPhthalates levels were positively associated with antral follicle count (AFC) (p<0.05) in oocyte donors when adjusted for age, BMI, and race/ethnicity. RNA-seq analysis revealed 248 differentially expressed genes (DEGs) in cumulus cells of adolescents within the top quartile (n=4) of FF ƩPhthalates levels compared to the adolescents within the bottom half (n=9). Genes enriched in pathways involved in cell motility and development were significantly downregulated. ConclusionAdolescents undergoing fertility preservation cycles demonstrate higher levels of phthalate metabolites in their follicular fluid compared to oocyte donors. Phthalate metabolite levels in FF are associated with higher AFC levels in oocyte donors.
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