Received 14 October 2014, Revised 20 February 2015, Accepted 21 February 2015, Available online 3 March 2015 Prenatal phthalate exposure and reproductive function in young men Jonatan Axelssona, Lars Rylanderb, Anna Rignell-Hydbomb, Christian H. Lindhb, Bo A.G. Jönssonb, Aleksander Giwercmana Abstract Background Prenatal exposure to phthalates is suggested to negatively impact male reproductive function, but human data are lacking. Objectives To study associations between prenatal exposure to diethylhexyl phthalate (DEHP) and diisononyl phthalate (DiNP), and reproductive parameters of adolescent men. Methods Using linear regression models adjusted for potential confounders, we studied associations between levels of DEHP- and DiNP metabolites in maternal sera from mean 12 weeks of pregnancy, and testicular size, semen quality and reproductive hormones in 112 adolescent sons, recruited from the general population. Results Men in the highest exposure tertile of one DiNP metabolite [mono-(carboxy-iso-octyl) phthalate], compared with men in the lowest tertile had: 4.3 mL (95% CI: 0.89, 7.6 mL; p<0.001) lower total testicular volume; 30% (95% CI: 3.6, 63%; p=0.02) higher levels of follicle-stimulating hormone; and 0.87 mL (95% CI: 0.28, 1.5 mL; p=0.004) lower semen volume. Men in the highest exposure tertile of one DEHP metabolite [mono-(2-ethyl-5-hydroxylhexyl) phthalate] had 0.70 mL (95% CI: 0.090, 1.3 mL; p=0.03) lower semen volume than men in the lowest exposure tertile. The levels of two DiNP metabolites [mono-(hydroxy-iso-nonyl) phthalate and mono-(oxo-iso-nonyl) phthalate] were linearly associated with luteinizing hormone (p<0.01). Abbreviations DEHP, diethylhexyl phthalate; DFI, DNA fragmentation index; DiNP, diisononyl phthalate; FSH, follicle-stimulating hormone; HDS, High DNA stainability; LC/MS/MS, liquid chromatography–tandem mass spectrometry; LH, luteinizing hormone; LOD, limit of detection; MECPP, mono-(2-ethyl-5-carboxypentyl) phthalate; MCiOP, mono-(carboxy-iso-octyl) phthalate; MEHHP, mono-(2-ethyl-5-hydroxylhexyl) phthalate; MHiNP, mono-(hydroxy-iso-nonyl) phthalate; MEOHP, mono-(2-ethyl-5-oxohexyl) phthalate; MOiNP, mono-(oxo-iso-nonyl) phthalate; MPW, masculinization programming window; SHBG, sex hormone-binding globulin; T, testosterone Conclusion Prenatal levels of some metabolites of DEHP and DiNP seemed negatively associated with reproductive function of adolescent men.
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