To determine if phthalates and bisphenol A accumulate in human follicular fluid after brief exposure to medical plastics during an IVF cycle
Prospective collection of follicular fluid from five infertile women undergoing oocyte retrieval at a University IVF laboratory and analysis of Phthalate & Bisphenol A levels.
All phthalate levels were detected at levels less than 15 ng/mL and Bisphenol A levels were undetectable in all five samples. The concentrations of phthalates are 200–1000 fold less than the minimum levels reported to cause reproductive toxicity in vitro to cumulus-oocyte complexes of laboratory animals.
In reproductive age women undergoing infertility treatments there is little transfer or accumulation of phthalates, phthalate metabolites or bisphenol A into the microenvironment of the human preovulatory oocyte and the levels are not clinically significant. Further investigation of phthalate and bisphenol A accumulation in vivo in human follicular fluid may not be productive.
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Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites. Epidemiology. 2006;17:682–91.
Wirth JJ, Rossano MG, Potter R, et al. A pilot study associating urinary concentrations of phthalate metabolites and semen quality. Syst Biol Repro Med. 2008;54:143–54.
Kim EJ, Kim JW, Lee SK. Inhibition of oocyte development in Japanese medaka (Oryzias latipes) exposed to di-2-ethylhexyl phthalate. Environ Int. 2002;28:359–65.
Anas MK, Suzuki C, Yoshioka K, Iwamura S. Effect of mono-(2-ethylhexyl) phthalate on bovine oocyte maturation in vitro. Reprod Toxicol. 2003;17:305–10.
Hunt PA, Koehler KE, Susiarjo M, et al. Bisphenol a exposure causes meiotic aneuploidy in the female mouse. Curr Biol. 2003;13:546–53.
Can A, Semiz O, Cinar O. Bisphenol-A induces cell cycle delay and alters centrosome and spindle microtubular organization in oocytes during meiosis. Mol Human Reprod. 2005;11:389–96.
Mohri T, Yoshida S. Estrogen and bisphenol A disrupt spontaneous [Ca(2+)](i) oscillations in mouse oocytes. Biochem Biophys Res Commun. 2005;326:166–73.
Mlynarcíková A, Kolena J, Ficková M, Scsuková S. Alterations in steroid hormone production by porcine ovarian granulosa cells caused by bisphenol A and bisphenol A dimethacrylate. Mol Cell Endocrinol. 2005;244:57–62.
Mlynarcíková A, Ficková M, Scsuková S. The effects of selected phenol and phthalate derivatives on steroid hormone production by cultured porcine granulosa cells. Altern Lab Anim. 2007;35:71–7.
Eichenlaub-Ritter U, Vogt E, Cukurcam S, Sun F, Pacchierotti F, Parry J. Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy. Mutat Res. 2008;651:82–92.
Lenie S, Cortvrindt R, Eichenlaub-Ritter U, Smitz J. Continuous exposure to bisphenol A during in vitro follicular development induces meiotic abnormalities. Mutat Res. 2008;651:71–81.
Lenie S, Smitz J. Steroidogenesis-disrupting compounds can be effectively studied for major fertility-related endpoints using in vitro cultured mouse follicles. Toxicol Lett. 2009;185:143–52.
Mlynarčíková A, Nagyová E, Ficková M, Scsuková S. Effects of selected endocrine disruptors on meiotic maturation, cumulus expansion, synthesis of hyaluronan and progesterone by porcine oocyte-cumulus complexes. Toxicol In Vitro. 2009;23:371–7.
Davis BJ, Maronpot RR, Heindel JJ. Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats. Toxicol Appl Pharmacol. 1994;128:216–23.
Davis BJ, Weaver R, Gaines LJ, Heindel JJ. Mono-(2-ethylhexyl) phthalate suppresses estradiol production independent of FSH-cAMP stimulation in rat granulosa cells. Toxicol Appl Pharmacol. 1994;128:224–8.
Lovekamp TN, Davis BJ. Mono-(2-ethylhexyl) phthalate suppresses aromatase transcript levels and estradiol production in cultured rat granulosa cells. Toxicol Appl Pharmacol. 2001;172:217–24.
Akingbemi BT, Sottas CM, Koulova AI, Klinefelter GR, Hardy MP. Inhibition of testicular steroidogenesis by the xenoestrogen bisphenol A is associated with reduced pituitary luteinizing hormone secretion and decreased steroidogenic enzyme gene expression in rat Leydig cells. Endocrinology. 2004;145:592–603.
Gunnarsson D, Leffler P, Ekwurtzel E, Martinsson G, Liu K, Selstam G. Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes. Reproduction. 2008;135:693–703.
Svechnikov K, Svechnikova I, Söder O. Inhibitory effects of mono-ethylhexyl phthalate on steroidogenesis in immature and adult rat Leydig cells in vitro. Reprod Toxicol. 2008;25:485–90.
Furuya M, Sasaki F, Hassanin AM, Kuwahara S, Tsukamoto Y. Effects of bisphenol-A on the growth of comb and testes of male chicken. Can J Vet Res. 2003;67:68–71.
Kato H, Ota T, Furuhashi T, Ohta Y, Iguchi T. Changes in reproductive organs of female rats treated with bisphenol A during the neonatal period. Reprod Toxicol. 2003;17:283–8.
Stoker C, Rey F, Rodriguez H, et al. Sex reversal effects on Caiman latirostris exposed to environmentally relevant doses of the xenoestrogen bisphenol A. Gen Comp Endocrinol. 2003;133:287–96.
Susiarjo M, Hassold TJ, Freeman E, Hunt PA. Bisphenol A exposure in utero disrupts early oogenesis in the mouse. PLoS Genet. 2007;3:e5.
Stoker C, Beldoménico PM, Bosquiazzo VL, et al. Developmental exposure to endocrine disruptor chemicals alters follicular dynamics and steroid levels in Caiman latirostris. Gen Comp Endocrinol. 2008;156:603–12.
Tsutsumi O. Assessment of human contamination of estrogenic endocrine-disrupting chemicals and their risk for human reproduction. J Steroid Biochem Mol Biol. 2005;93:325–30.
Högberg J, Hanberg A, Berglund M, et al. Phthalate diesters and their metabolites in human breast milk, blood or serum, and urine as biomarkers of exposure in vulnerable populations. Environ Health Perspect. 2008;116:334–9.
Lee YJ, Ryu HY, Kim HK, et al. Maternal and fetal exposure to bisphenol A in Korea. Reprod Toxicol. 2008;25:413–9.
Hines EP, Calafat AM, Silva MJ, Mendola P, Fenton SE. Concentrations of phthalate metabolites in milk, urine, saliva, and Serum of lactating North Carolina women. Environ Health Perspect. 2009;117:86–92.
Kato K, Silva MJ, Needham LL, Calafat AM. Determination of 16 phthalate metabolites in urine using automated sample preparation and on-line preconcentration/high-performance liquid chromatography/tandem mass spectrometry. Anal Chem. 2005;77:2985–91.
Ikezuki Y, Tsutsumi O, Takai Y, Kamei Y, Taketani Y. Determination of bisphenol A concentrations in human biological fluids reveals significant early prenatal exposure. Hum Reprod. 2002;17:2839–41.
Follicular fluids obtained from 5 infertility patients previously exposed to medical plastics and undergoing ooctye retrieval demonstrate little transfer or accumulation of phthalates, phthalates metabolites or bisphenol A into the follicular microenvironment.
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Krotz, S.P., Carson, S.A., Tomey, C. et al. Phthalates and bisphenol do not accumulate in human follicular fluid. J Assist Reprod Genet 29, 773–777 (2012). https://doi.org/10.1007/s10815-012-9775-1
- Bisphenol A
- Follicular fluid
- Reproductive toxins