Skip to main content Accessibility help
×
Hostname: page-component-76fb5796d-zzh7m Total loading time: 0 Render date: 2024-04-25T13:56:06.982Z Has data issue: false hasContentIssue false

7 - Role of exposure to environmental chemicals in developmental origins of health and disease

Published online by Cambridge University Press:  08 August 2009

Jerrold J. Heindel
Affiliation:
National Institute of Environmental Health Sciences
Cindy Lawler
Affiliation:
National Institute of Environmental Health Sciences
Peter Gluckman
Affiliation:
University of Auckland
Mark Hanson
Affiliation:
University of Southampton
Get access

Summary

Introduction

Between two and five per cent of all live-born infants have a major developmental defect. Up to 40 per cent of these defects have been estimated to result from maternal exposure(s) to harmful environmental agents that directly or indirectly create an unfavourable intrauterine environment. A spectrum of adverse effects can occur, including death, structural malformation, and/or functional alteration of the fetus/embryo. The traditional focus of the science of developmental toxicology has been on the role of agents (environmental or drugs) that cause either premature death of the fetus or birth defects. In recent years, attention has turned to examining the effects of in-utero or neonatal exposure to environmental agents on functional changes in tissues, e.g. permanent changes in tissue function that are not the result of overtly or grossly teratogenic effects but that result in increased susceptibility to disease/dysfunction later in life.

The epidemiology data that support the concept of the fetal basis of adult disease, together with the preliminary data showing alterations in gene expression and tissue imprinting due to in-utero exposures to some environmental agents, provide an attractive framework for understanding delayed functional effects of toxicant exposures. We propose that exposure to certain environmental chemicals, alone or in combination with altered nutrition, leads to aberrant developmental programming that permanently alters gland, organ or system potential.

Type
Chapter
Information
Publisher: Cambridge University Press
Print publication year: 2006

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abbott, D. H., Dumesic, D. A., Eisner, J. W., Kemnitz, R. J. and Goy, R. W. (1997). The prenatally androgenized female rhesus monkey as a model for polycystic ovarian syndrome. In Androgen Excess Disorders in Women, (ed. Assiz, R., Nestler, J. E. and Dewailly, D.). Philadelphia, PA: Lippincott-Raven, pp. 369–82.Google Scholar
Abbott, D. H., Dumesic, D. A. and Franks, S. (2002). Developmental origins of polycystic ovary syndrome: a hypothesis. J. Endocrinol., 174, 1–5.CrossRefGoogle Scholar
Akingbemi, B. T., Sottas, C. M., Koulova, A. I., Klindfelter, G. R. and Hardy, M. P. (2004). 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, 145, 592–603.CrossRefGoogle ScholarPubMed
Aldridge, J. E., Seidler, F. J. and Slotkin, T. A. (2004). Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling. Environ. Health Perspect., 112, 148–55.CrossRefGoogle ScholarPubMed
Alworth, L. C., Howdeshell, K. L., Ruhlen, R. L.et al. (2002). Uterine responsiveness to estradiol and DNA methylation are altered by fetal exposure to diethylstilbestrol and methoxychlor in CD-1 mice: effects of low versus high doses. Toxicol. Appl. Pharmacol., 183, 10–22.CrossRefGoogle ScholarPubMed
Anwar, A., McTernan, P. G., Anderson, L. A.et al. (2001). Site-specific regulation of oestrogen receptor a and b by estradiol in human adipose tissue. Diabetes Obes. Metab., 3, 338–49.CrossRefGoogle Scholar
Anway, M. D., Cupp, A. S., Uzumcu, M. and Skinner, M. K. (2005). Epigenetic transgenerational actions of endocrine disruptors on male fertility. Science, 308, 1466–9.CrossRefGoogle ScholarPubMed
Baillie-Hamilton, P. F. (2002). Chemical toxins: a hypothesis to explain the global obesity epidemic. J. Altern. Complement. Med., 8, 185–92.CrossRefGoogle ScholarPubMed
Bern, H. (1992). The fragile fetus. In Chemically Induced Alterations in Sexual and Functional development: the Wildlife/Human Connection (ed. Colborn, T. and Clement, C.). Princeton: Princeton Scientific Publishing, pp. 9–15.Google Scholar
Bhathena, S. J. and Velasquez, M. T. (2002). Beneficial role of dietary phytoestrogens in obesity and diabetes. Am. J. Clin. Nutr., 76, 1191–201.CrossRefGoogle ScholarPubMed
Birnbaum, L. S. and Fenton, S. E. (2003). Cancer and developmental exposures to endocrine disruptors. Environ. Health Perspect., 111, 389–94.CrossRefGoogle ScholarPubMed
Brown, N. M., Manzolillo, P. A., Ahang, J. X., Wang, J. and Lamartiniere, C. A. (1998). Prenatal TCDD and predisposition to mammary cancer in the rat. Carcinogenesis, 19, 1623–9.CrossRefGoogle ScholarPubMed
Catalano, S., Marsico, S., Giodano, C.et al. (2003). Leptin enhances, via AP-1, expression of aromatase in the MCF-7 cell line. J. Biol. Chem., 278, 28668–76.CrossRefGoogle ScholarPubMed
Cory-Slechta, D. A., Virgolini, M. D., Thiruchelvam, M., Weston, D. D. and Bauter, M. R. (2004). Maternal stress modulates the effects of developmental lead exposure. Environ. Health Perspect., 112, 717–30.CrossRefGoogle ScholarPubMed
Davidson, P. W., Myers, G. J., Cox, C.et al. (1998). Effects of prenatal and postnatal methylmercury exposures from fish consumption on neurodevelopment: outcomes at 66 months of age in the Seychelles Child Development Study. JAMA, 280, 701–7.CrossRefGoogle Scholar
Delville, Y. (1999). Exposure to lead during development alters aggressive behavior in golden hamsters. Neurotoxicol. Teratol., 21, 445–9.CrossRefGoogle ScholarPubMed
Eisner, J. R., Barnett, M. A., Dumesic, D. A. and Abbott, D. H. (2002). Ovarian hyperandrogenism in adult female rhesus monkeys exposed to prenatal androgen excess. Fertil. Steril., 77, 167–72.CrossRefGoogle ScholarPubMed
Fenton, S. E., Hamm, J. T., Birnbaum, L. S. and Youngblood, G. l. (2002). Persistant abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Toxicol. Sci., 67, 63–74.CrossRefGoogle Scholar
Gehrs, B. C. and Smialowicz, R. J. (1999). Persistent suppression of delayed-type hypersensitivity in adult F344 rats after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicology, 134, 79–88.CrossRefGoogle ScholarPubMed
Gehrs, B. C., Riddle, M. M., Williams, W. C. and Smialowicz, R. J. (1997). Alterations in the developing immune system of the F344 rat after prenatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin II: effects on the pup and the adult. Toxicology, 122, 229–40.CrossRefGoogle ScholarPubMed
Grandjean, P., Weihe, P., White, R. F.et al. (1997). Cognitive deficits in 7-year old children with prenatal exposures to methylmercury. Neurotoxicol. Teratol., 19, 417–28.CrossRefGoogle Scholar
Gray, L. E., Ostby, J., Monosson, E. and Kelce, W. R. (1999). Environmental antiandrogens: low doses of the fungicide vinclozolin alter sex differentiation of the male rat. Toxicol. Ind. Health, 15, 48–64.CrossRefGoogle ScholarPubMed
Heindel, J. J. (2003). Endocrine disruptors and the obesity epidemic. Toxicol. Sci., 76, 247–9.CrossRefGoogle ScholarPubMed
Herbst, A. L., Ulfelder, H., Poskanzer, D. C. and Longo, L. D. (1971). Adenocarcinoma of the vagina: association of maternal stilbestrol therapy with tumour appearance in young women. N. Engl. J. Med., 284, 878–81.CrossRefGoogle ScholarPubMed
Hilakivi-Clarke, L., Cho, E., Onojafe, I., Raygada, M. and Clarke, R. (1999). Maternal exposure to genistein during pregnancy increases carcinogen-induced mammary tumourigenesis in female rat offspring. Oncol. Rep., 6, 1089–95.Google Scholar
Holladay, S. D. (1999). Prenatal immunotoxicant exposure and postnatal autoimmune disease. Environ. Health Perspect., 107 (suppl. 5), 687–91.CrossRefGoogle ScholarPubMed
Holladay, S. D., Blaylock, B. L., Comment, C. E., Heindel, J. J., Fox, W. M. and Luster, M. I. (1993). Selective prothymocyte targeting by prenatal diethylstilbestrol exposure. Cell. Immunol., 152, 131–42.CrossRefGoogle Scholar
Howdeshell, K. L., Hotchkiss, A. K., Thayer, K. A., Vandenbergh, J. G. and Saal, vom F. S. (1999). Exposure to bisphenol A advances puberty. Nature, 401, 763–4.Google ScholarPubMed
Hughes, C. L., Liu, G., Beall, S., Foster, W. G. and Davis, V. (2004). Effects of genistein or soy milk during late gestation and lactation on adult uterine organisation in the rat. Exp. Biol. Med., 229, 108–17.CrossRefGoogle ScholarPubMed
Hunt, P. A., Koehler, K. E., Susiarjo, M.et al. (2003). Bisphenol A exposure causes meiotic aneuploidy in the female mouse. Curr. Biol., 13, 546–53.CrossRefGoogle ScholarPubMed
Jacobson, J. L. and Jacobson, S. W. (2004). Prenatal exposure to polychlorinated biphenols and attention at school age. Obstet. Gynecol. Surv., 59, 412–13.CrossRefGoogle Scholar
Jefferson, W. N., Couse, J. F., Padilla-Banks, E., Korach, K. S. and Newbold, R. (2002). Neonatal exposure to genistein induces oestrogen receptor (ERa) expression and multioocyte follicles in the maturing mouse ovary: evidence for ERb-mediated and nonestrogenic actions. Biol. Reprod., 67, 1285–96.CrossRefGoogle Scholar
Jefferson, W. N., Padilla-Banks, E., Couse, J. F., Korach, K. S. and Newbold, R. R. (in press). Neonatal genistein exposure induces oestrogen receptor mediated alterations in gene expression in the developing mouse uterus: differential effects of low versus high doses. Mol. Endocrinol.Google Scholar
Jones, P. A. and Baylin, S. B. (2002). The fundamental role of epigenetic events in cancer. Nat. Rev. Genet., 3, 415–28.CrossRefGoogle Scholar
Joyner, J. K., Hutley, L. J. and Cameron, D. P. (2001). Estrogen receptors in human preadipocytes. Endocrine, 15, 225–30.CrossRefGoogle ScholarPubMed
Kaneko-Ishino, T., Kohda, T. and Ishino, F. (2003). The regulation and biological significance of genomic imprinting. J. Biochem., 133, 699–711.CrossRefGoogle ScholarPubMed
Karri, S., Johnson, H., Hendry, W. J., Williams, S. C. and Kahn, S. A. (2004). Neonatal exposure to diethylstilbestrol leads to impaired action of androgens in adult male hamsters. Reprod. Toxicol., 19, 53–63.CrossRefGoogle ScholarPubMed
Kelce, W. R., Gray, L. E. and Wilson, E. M. (1998). Antiandrogens as environmental endocrine disruptors. Reprod. Fertil. Dev., 10, 105–11.CrossRefGoogle ScholarPubMed
Kouki, T., Kishitake, M., Okamoto, M., Talebe, M. and Yamanouchiu, I. (2003). Effects of neonatal treatment with phytoestrogens, genestein and daidzein on sex difference in female rat brain function: estrous cycle and lordosis. Horm. Behav., 44, 140–5.CrossRefGoogle ScholarPubMed
Levin, E. D. (2005). Fetal nicotinic overload, blunted sympathetic responsivity and weight gain. Birth Defects Res. A Clin. Mol. Teratol., epub. June 2005.CrossRefGoogle Scholar
Li, S., Hansman, R., Newbold, R., Davis, B. and McLachlan, J. (2003). Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation of its exon-4 in mouse uterus. Mol. Carcinog., 38, 78–84.CrossRefGoogle ScholarPubMed
Lin, T. M., Rasmussen, N. T., Moore, R. W., Albrecht, R. M. and Peterson, R. E. (2003). Region-specific inhibition of prostatic epithelial bud formation in the urogenital sinus of C57BL/6 mice exposed in-utero to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Toxicol. Sci., 76, 171–81.CrossRefGoogle ScholarPubMed
Ling, Z. D., Chang, Q., Lipiton, J. W., Tong, C. W., Landers, T. M. and Carvey, P. M. (2004). Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain. Neuroscience, 124, 619–28.CrossRefGoogle ScholarPubMed
Lund, T. D., Munson, D. J., Adlercreutz, H., Handa, R. J. and Lephart, E. D. (2004). Androgen receptor expression in the rat prostate is down regulated by dietary phytoestrogens. Reprod. Biol. Endocrinol., 16, 5–11.CrossRefGoogle Scholar
Marchioro, M., Swanson, K. L., Aracava, Y. and Albuquerque, E. X. (1996). Glycine and calcium-dependent effects of lead on N-methyl-D-aspartate receptor function in rat hippocampal neurons. J. Pharmacol. Exp. Ther., 279, 143–53.Google ScholarPubMed
Markey, C. M., Luque, E. H., Munoz de Toro, M., Sonnenschein, C. and Soto, S. M. (2001). In utero exposure to bisphenol A alters the development and tissue organisation of the mouse mammary gland. Biol. Reprod., 65, 1215–23.CrossRefGoogle ScholarPubMed
Masuno, H., Kidani, T., Sekiya, , et al. (2002). Bisphenol A in combination with insulin can accelerate the conversion of 3T3-L1 fibroblasts to adipocytes. J. Lipid Res., 43, 676–84.Google ScholarPubMed
McLachlan, J. A., Newbold, R. R. and Bullock, B. C. (1980). Long term effects on the female mouse genital tract associated with prenatal exposure to diethylstilbestrol. Cancer Res., 40, 3988–99.Google ScholarPubMed
McLachlan, J. A., Newbold, R. R., Burrow, M. E. and Li, S. F. (2001). From malformations to molecular mechanisms in the male: three decades of research on endocrine disruptors. APMIS, 109, 263–72.CrossRefGoogle Scholar
Miyagawa, S., Katsu, Y., Watanabe, H. and Iguchi, T. (2004). Estrogen-independent activation of erbBs signaling and estrogen receptor α in the mouse vagina exposed neonatally to diethylstilbestrol. Oncogene, 23, 340–9.CrossRefGoogle ScholarPubMed
Mori, C., Komiyama, M., Adachi, T.et al. (2002). Application of toxicogenomic analysis to risk assessment of delayed long-term effects of multiple chemicals, including endocrine disruptors in human fetuses. Environ. Health Perspect., 111, 803–9.Google Scholar
Murphy, S. K. and Jirtle, R. L. (2003). Imprinting evolution and the price of silence. Bioessays, 25, 577–88.CrossRefGoogle Scholar
Naaz, A., Yellayi, S., Sakroczymski, M. A.et al. (2003). The soy isoflavone genistein decreases adipose deposition in mice. Endocrinology, 144, 3315–20.CrossRefGoogle ScholarPubMed
Nagai, A., Ikeda, Y., Aso, T., Eto, K. and Ikeda, M. A. (2003). Exposure of neonatal rats to diethylstilbestrol affects the expression of genes involved in ovarian differentiation. J. Med. Dent. Sci., 50, 35–40.Google ScholarPubMed
Nakao, M. (2001). Epigenetics: interaction of DNA methylation and chromatin. Gene, 278, 25–31.CrossRefGoogle ScholarPubMed
Needham, L. L. and Sexton, K. (2000). Assessing children's exposure to hazardous environmental chemicals: an overview of selected research challenges and complexities. J. Expos. Anal. Environ. Epidemiol., 10, 611–29.CrossRefGoogle ScholarPubMed
Needleman, H. L., McFarland, C., Ness, R. B., Fienberg, S. E. and Tobin, M. J. (2002). Bone lead levels in adjudicated delinquents. A case control study. Neurotoxicol. Teratol., 24, 711–17.CrossRefGoogle ScholarPubMed
Newbold, R. R., Bullock, B. C. and McLachlan, J. A. (1990). Uterine adenocarcinoma in mice following developmental treatment with oestrogens: a model for hormonal carcinogenesis. Cancer Res., 50, 7677–81.Google ScholarPubMed
Newbold, R. R., Banks, E. P., Bullock, B. and Jefferson, W. N. (2001). Uterine adenocarcinoma in mice treated neonatally with genistein. Cancer Res., 61, 4325–8.Google ScholarPubMed
Newbold, R. R., Jefferson, W. J., Padilla-Banks, E. and Haseman, J. (2004). Developmental exposure to diethylstilbestrol (DES) alters uterine response to oestrogens in prepubescent mice: low versus high dose effects. Rep. Toxicol. 18, 399–406.CrossRefGoogle ScholarPubMed
Novik, K. L., Nimmrich, I., Genc, B.et al. (2002). Epigenomics: genome-wide study of methylation phenomena. Curr. Issues. Mol. Biol., 4, 111–28.Google ScholarPubMed
Oken, E. and Gillman, M. W. (2003). Fetal origins of obesity. Obes. Res., 11, 496–506.CrossRefGoogle ScholarPubMed
Padmanabhan, V., Evans, E., Taylor, J. A. and Robinson, J. E. (1998). Prenatal exposure to androgens leads to the development of cystic ovaries in the sheep. Biol. Reprod. 56 (Suppl. l), 194–9.Google Scholar
Palmer, J. R., Hatch, E. E., Rosenberg, C. L.et al. (2002). Risk of breast cancer in women exposed to diethylstilbestrol in utero: preliminary results (United States). Cancer Causes Control, 13, 753–8.CrossRefGoogle Scholar
Qiao, D, Seidler, F. J., Tate, C. A., Cousins, M. M. and Slotkin, T. A. (2003). Fetal chlorpyrifos exposure: adverse effects on brain cell development and cholinergic biomarkers emerge postnatally and continue into adolescence and adulthood. Environ. Health Perspect., 111, 536–44.CrossRefGoogle ScholarPubMed
Ramos, J. G., Varayoud, J., Sonnenschein, C., Soto, A. M., Munoz de Toro, M. M. and Luque, E. H. (2001). Prenatal exposure to low doses of bisphenol A alters the periductal stroma and glandular cell function in the rat ventral prostate. Biol. Reprod., 65, 1271–7.CrossRefGoogle ScholarPubMed
Reik, W., Santos, F. and Dean, W. (2003). Mammalian epigenomics: reprogramming the genome for development and therapy. Theriogenology, 59, 21–32.CrossRefGoogle ScholarPubMed
Rice, D. C. (1996). Behavioral effects of lead: commonalities between experimental and epidemiologic data. Environ. Health Perspect., 104 (Suppl. 2), 337–51.CrossRefGoogle ScholarPubMed
Ris, M. D., Dietrich, K. N., Succop, P. A., Berger, O. G. and Bornschein, R. I. (2004). Early exposure to lead and neuropsychological outcome in adolescence. J. Int. Neuropsychol. Soc., 10, 261–70.CrossRefGoogle ScholarPubMed
Rogers, I., and the EURO-BLCS Study Group. (2003). The influence of birthweight and intrauterine environment on adiposity and fat distribution in later life. Int. J. Obes., 27, 755–77.CrossRefGoogle ScholarPubMed
Rubin, B. R., Murray, M. K., Damassa, D. A., King, J. C. and Soto, A. (2001). Perinatal exposure to low doses of bisphenol A affects body weight, patterns of estrous cyclicity, and plasma LH levels. Environ. Health Perspect., 109, 675–80.CrossRefGoogle ScholarPubMed
Sakurai, K., Kawazuma, T., Adachi, T.et al. (2004). Bishenol A affects glucose transport in mouse 3T3-F442A adipocytes. Br. J. Pharmacol., 141, 209–14.CrossRefGoogle ScholarPubMed
Shuanfang, L, Hansman, R., Newbold, R., Davis, B. and McLachlan, J. A. (2003). Neonatal diethylstilbestrol exposure induces persistent elevation of c-fos expression and hypomethylation in its exon-4 in mouse uterus. Mol. Carcinog., 38, 78–84.Google Scholar
Silverstone, A. E., Gavalchin, J. and Gasiewicz, T. A. (1998). DES and estradiol potentiate a lupus-like autoimmune nephritis in NZB x SWR (SNF1) mice. Toxicologist, 42, 403.Google Scholar
Stewart, P. W., Reihman, J., Lonky, E. I., Darvill, T. J. and Pagano, J. (2003). Cognitive development in preschool children prenatally exposed to PCBs and Me Hg. Neurotoxicol. Teratol., 25, 11–22.CrossRefGoogle Scholar
Takai, Y., Tsutsumi, O., Ikezuki, Y.et al. (2001). Preimplantation exposure to bisphenol A advances postnatal development. Reprod. Toxicol., 15, 71–4.CrossRefGoogle ScholarPubMed
Thiruchelvan, M., McCormack, A., Richfield, E. K.et al. (2003). Age-related irreversible progressive nigrostriatal dopaminergic neurotoxicity in the paraquat and maneb model of the Parkinson's disease phenotype. Eur. J. Neurosci., 18, 589–600.CrossRefGoogle Scholar
Timms, B. G., Peterson, R. E. and Saal, vom F. S. (2002). 2,3,7,8-tetrachlorodibenzo-p-dioxin interacts with endogenous estradiol to disrupt prostate gland morphogenesis in male rat fetuses. Toxicol. Sci., 67, 264–74.CrossRefGoogle ScholarPubMed
Toschke, A. M., Koletzko, B., Slikker, W. Jr., Hermann, M. and Kries, R. (2002). Childhood obesity is associated with maternal smoking in pregnancy. Eur. J. Pediatr., 161, 445–8.CrossRefGoogle ScholarPubMed
Turiel, J. and Wingard, D. L. (1988). Immune response in DES-exposed women. Fertil. Steril., 49, 928–9.Google ScholarPubMed
Uzumcu, M., Suzuki, H. and Skinner, M. (2004). Effect of the anti-androgenic endocrine disruptor vinclozolin on embryonic testis cord formation and postnatal testis development and function. Reprod. Toxicol., 18, 765–74,CrossRefGoogle ScholarPubMed
Driel, R., Fransz, P. F. and Verschure, P. J. (2003). The eukaryotic genome: a system regulated at different hierarchical levels. J. Cell Sci., 116, 4067–75.CrossRefGoogle ScholarPubMed
Saal, vom F. S., Timms, B. G., Montano, M. M.et al. (1997). Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses. Proc. Natl. Acad. Sci. USA, 94, 2056–61.CrossRefGoogle Scholar
Welshons, W. V., Nagel, S. C., Thayer, A., Judy, B. M. and Saal, vom F. S. (1999). Low-dose bioactivity of xenoestrogens in animals: fetal exposure to low doses of methoxychlor and other xenoestrogens increases adult prostate size in mice. Toxicol. Ind. Health, 15, 12–25.CrossRefGoogle ScholarPubMed
Wideroe, M., Vik, T., Jacobsen, G. and Bakketeig, L. (2003). Does maternal smoking during pregnancy cause childhood overweight?Pediatr. Perinat. Epidemiol., 17, 171–9.CrossRefGoogle ScholarPubMed
Williams, C. and Kanagasabai, T. (1984). Maternal adipose tissue response to nicotine administration in the pregnant rat: effects on fetal body fat and cellularity. Br. J. Nutr., 51, 7–13.CrossRefGoogle ScholarPubMed
Woodham, C., Birch, L. and Prins, G. S. (2003). Neonatal oestrogen down-regulates prostatic androgen receptor through a proteosome-mediated protein degradation pathway. Endocrinol., 144, 4841–50.CrossRefGoogle ScholarPubMed
Younglai, E. V., Foster, W. G., Hughes, E. G., Trim, K. and Farrell, J. F. (2002). Levels of environmental contaminants in human follicular fluid, serum, and seminal plasma of couples undergoing in vitro fertilization. Arch. Environ. Contam. Toxicol., 43, 121–6.CrossRefGoogle ScholarPubMed

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×