Journal of Assisted Reproduction and Genetics

, Volume 29, Issue 8, pp 773–777 | Cite as

Phthalates and bisphenol do not accumulate in human follicular fluid

  • Stephan P. Krotz
  • Sandra A. Carson
  • Cynthia Tomey
  • John E. BusterEmail author
Gonadal Physiology and Disease



To determine if phthalates and bisphenol A accumulate in human follicular fluid after brief exposure to medical plastics during an IVF cycle

Study design

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.


Phthalates Bisphenol A Follicular fluid Reproductive toxins 


  1. 1.
    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.PubMedCrossRefGoogle Scholar
  2. 2.
    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.CrossRefGoogle Scholar
  3. 3.
    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.PubMedCrossRefGoogle Scholar
  4. 4.
    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.PubMedCrossRefGoogle Scholar
  5. 5.
    Hunt PA, Koehler KE, Susiarjo M, et al. Bisphenol a exposure causes meiotic aneuploidy in the female mouse. Curr Biol. 2003;13:546–53.PubMedCrossRefGoogle Scholar
  6. 6.
    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.CrossRefGoogle Scholar
  7. 7.
    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.PubMedCrossRefGoogle Scholar
  8. 8.
    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.PubMedCrossRefGoogle Scholar
  9. 9.
    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.PubMedGoogle Scholar
  10. 10.
    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.PubMedCrossRefGoogle Scholar
  11. 11.
    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.PubMedCrossRefGoogle Scholar
  12. 12.
    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.PubMedCrossRefGoogle Scholar
  13. 13.
    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.PubMedCrossRefGoogle Scholar
  14. 14.
    Davis BJ, Maronpot RR, Heindel JJ. Di-(2-ethylhexyl) phthalate suppresses estradiol and ovulation in cycling rats. Toxicol Appl Pharmacol. 1994;128:216–23.PubMedCrossRefGoogle Scholar
  15. 15.
    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.PubMedCrossRefGoogle Scholar
  16. 16.
    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.PubMedCrossRefGoogle Scholar
  17. 17.
    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.PubMedCrossRefGoogle Scholar
  18. 18.
    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.PubMedCrossRefGoogle Scholar
  19. 19.
    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.PubMedCrossRefGoogle Scholar
  20. 20.
    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.PubMedGoogle Scholar
  21. 21.
    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.PubMedCrossRefGoogle Scholar
  22. 22.
    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.PubMedCrossRefGoogle Scholar
  23. 23.
    Susiarjo M, Hassold TJ, Freeman E, Hunt PA. Bisphenol A exposure in utero disrupts early oogenesis in the mouse. PLoS Genet. 2007;3:e5.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedCrossRefGoogle Scholar
  25. 25.
    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.PubMedCrossRefGoogle Scholar
  26. 26.
    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.PubMedCrossRefGoogle Scholar
  27. 27.
    Lee YJ, Ryu HY, Kim HK, et al. Maternal and fetal exposure to bisphenol A in Korea. Reprod Toxicol. 2008;25:413–9.PubMedCrossRefGoogle Scholar
  28. 28.
    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.PubMedGoogle Scholar
  29. 29.
    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.PubMedCrossRefGoogle Scholar
  30. 30.
    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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Stephan P. Krotz
    • 1
  • Sandra A. Carson
    • 2
  • Cynthia Tomey
    • 3
  • John E. Buster
    • 2
    Email author
  1. 1.Advance Fertility Center of TexasHoustonUSA
  2. 2.Division of Reproductive Endocriniology and InfertilityWarren Alpert Medical School of Brown University, Women & Infants Hospital of Rhode IslandProvidenceUSA
  3. 3.AXYS Technology Inc.SidneyCanada

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