Xenobiotic activity in serum and sperm chromatin integrity in European and inuit populations

Lipophilic persistent organic pollutants (POPs) are ubiquitous in the environment and suspected to interfere with hormone activities and reproduction. In previous studies we demonstrated that POP exposure can affect sperm DNA integrity and differences between Inuits and Europeans in sperm DNA integrity and xenobiotic activity were observed. The aim of this study was to investigate possible relations between human sperm chromatin integrity and the xenobiotic serum activity of lipophilic POPs assessed as effects on the estrogen (ER), androgen (AR), and/or aryl hydrocarbon (AhR) receptors. Human sperm chromatin integrity was assessed as DNA fragmentation index (%DFI) and high DNA stainability (%HDS) using the flow cytometric sperm chromatin structure assay (SCSA). Xenobiotic receptor activities were determined using chemically activated luciferase gene expression (CALUX) assay. The study included 53 Greenlandic Inuits and 247 Europeans (Sweden, Warsaw (Poland) and Kharkiv (Ukraine)). A heterogeneous pattern of correlations was found. For Inuits, ER and AhR activities and %DFI were inversely correlated, whereas a positive correlation between AR activity and %DFI was found for Europeans. In contrast, no correlation between receptor activities and %HDS was observed for Inuits but for Europeans positive and negative correlations were observed between ER and AR activities and %HDS, respectively. We suggest that the different patterns of xenobiotic serum activities, in combination with diet associated factors and/or genetics, might be connected to the observed differences in sperm chromatin integrity between the Inuits and Europeans. Mol. Reprod. Dev. 75: 669–680, 2008. © 2007 Wiley‐Liss, Inc.

[1]  J Ashby,et al.  Some alkyl hydroxy benzoate preservatives (parabens) are estrogenic. , 1998, Toxicology and applied pharmacology.

[2]  N. Olea,et al.  Human exposure to endocrine disrupters: Standardisation of a marker of estrogenic exposure in adipose tissue Note , 2001 .

[3]  H. Autrup,et al.  Effect of toxaphene on estrogen receptor functions in human breast cancer cells. , 1997, Carcinogenesis.

[4]  T. Klonisch,et al.  Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction. , 2005, Reproduction.

[5]  C Sonnenschein,et al.  The pesticides endosulfan, toxaphene, and dieldrin have estrogenic effects on human estrogen-sensitive cells. , 1994, Environmental health perspectives.

[6]  Jorma Toppari,et al.  Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age , 2005, Environmental health perspectives.

[7]  A. Kortenkamp,et al.  Mixtures of four organochlorines enhance human breast cancer cell proliferation. , 2001, Environmental health perspectives.

[8]  Christopher M Thomas,et al.  Male factor subfertility: possible causes and the impact of nutritional factors. , 2000, Fertility and sterility.

[9]  A. Giwercman,et al.  Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. , 2007, Human reproduction.

[10]  S. Andò,et al.  Endogenous Coactivator ARA70 Interacts with Estrogen Receptor α (ERα) and Modulates the Functional ERα/Androgen Receptor Interplay in MCF-7 Cells* , 2005, Journal of Biological Chemistry.

[11]  T. Schrader,et al.  Effects of Aroclors and individual PCB congeners on activation of the human androgen receptor in vitro. , 2003, Reproductive toxicology.

[12]  Jens Peter Bonde,et al.  Correlation between sperm motility and sperm chromatin structure assay parameters. , 2003, Fertility and sterility.

[13]  H. Krishnamurthy,et al.  Qualitative and Quantitative Decline in Spermatogenesis of the Follicle-Stimulating Hormone Receptor Knockout (FORKO) Mouse1 , 2000, Biology of reproduction.

[14]  A. Mantovani,et al.  Long-lasting effects of lindane on mouse spermatogenesis induced by in utero exposure. , 2003, Reproductive toxicology.

[15]  J. C. Hansen,et al.  Selenium status in Greenland Inuit. , 2004, The Science of the total environment.

[16]  R. Kruse,et al.  Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure , 2005, Environmental health perspectives.

[17]  Mogens Erlandsen,et al.  Xenoestrogenic activity in blood of European and Inuit populations , 2006, Environmental health : a global access science source.

[18]  Rivka L. Glaser,et al.  Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[19]  Jesper Bo Nielsen,et al.  Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts , 2003, Environmental health : a global access science source.

[20]  Tanja Krüger,et al.  Xenoandrogenic Activity in Serum Differs across European and Inuit Populations , 2007, Environmental health perspectives.

[21]  A. Kortenkamp,et al.  Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. , 2002, Environmental health perspectives.

[22]  A. Giwercman,et al.  The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios. , 1998, Human reproduction.

[23]  E. Bonefeld‐Jørgensen,et al.  SPE-HPLC purification of endocrine-disrupting compounds from human serum for assessment of xenoestrogenic activity , 2006, Analytical and bioanalytical chemistry.

[24]  G. Beckett,et al.  Selenium and endocrine systems. , 2005, The Journal of endocrinology.

[25]  Jens Peter Bonde,et al.  Dioxin-like activities in serum across European and Inuit populations , 2006, Environmental health : a global access science source.

[26]  D. Sakkas,et al.  Sperm nuclear DNA damage in the human. , 2003, Advances in experimental medicine and biology.

[27]  J. McLachlan,et al.  Altered Breast Development in Young Girls from an Agricultural Environment , 2006, Environmental health perspectives.

[28]  M. Davidoff,et al.  Induction of male germ cell apoptosis by testosterone withdrawal after ethane dimethanesulfonate treatment in adult rats. , 2004, Endocrine regulations.

[29]  E. Bonefeld‐Jørgensen,et al.  Effect of pesticides on estrogen receptor transactivation in vitro: A comparison of stable transfected MVLN and transient transfected MCF-7 cells , 2005, Molecular and Cellular Endocrinology.

[30]  D Stewart Irvine,et al.  Integrating new tests of sperm genetic integrity into semen analysis: breakout group discussion. , 2003, Advances in experimental medicine and biology.

[31]  R. Sharpe Pathways of endocrine disruption during male sexual differentiation and masculinization. , 2006, Best practice & research. Clinical endocrinology & metabolism.

[32]  A. Roverato,et al.  Androgen receptor gene CAG and GGC repeat lengths in cryptorchidism. , 2005, European journal of endocrinology.

[33]  M Silva-Ramos,et al.  The CAG repeat within the androgen receptor gene and its relationship to cryptorchidism. , 2006, International braz j urol : official journal of the Brazilian Society of Urology.

[34]  R. Hauser The environment and male fertility: recent research on emerging chemicals and semen quality. , 2006, Seminars in reproductive medicine.

[35]  S. Perreault,et al.  Episodic air pollution is associated with increased DNA fragmentation in human sperm without other changes in semen quality. , 2005, Human reproduction.

[36]  N. Tarozzi,et al.  Abnormal spermatozoa in the ejaculate: abortive apoptosis and faulty nuclear remodelling during spermatogenesis. , 2003, Reproductive biomedicine online.

[37]  Tanja Krüger,et al.  Relation between serum xenobiotic-induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations. , 2007 .

[38]  G. Block,et al.  Effect of antioxidant intake on sperm chromatin stability in healthy nonsmoking men. , 2005, Journal of andrology.

[39]  A. Agarwal,et al.  Role of sperm chromatin abnormalities and DNA damage in male infertility. , 2003, Human reproduction update.

[40]  L. Gray,et al.  Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist , 1995, Nature.

[41]  A. Giwercman,et al.  Androgen receptor gene CAG repeat length as a modifier of the association between persistent organohalogen pollutant exposure markers and semen characteristics , 2007, Pharmacogenetics and genomics.

[42]  A. Sasco,et al.  Breast Cancer Risk and the Combined Effect of Environmental Estrogens , 2004, Cancer Causes & Control.

[43]  Ana Rivas,et al.  Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect , 2004, Analytical and bioanalytical chemistry.

[44]  F. Comhaire,et al.  Deterioration of sperm quality in young healthy Belgian men. , 1996, Human reproduction.

[45]  A. Giwercman,et al.  The impact of testicular and accessory sex gland function on sperm chromatin integrity as assessed by the sperm chromatin structure assay (SCSA). , 2002, Human reproduction.

[46]  M. van den Berg,et al.  Impact of Polychlorinated Biphenyls Contamination on Estrogenic Activity in Human Male Serum , 2005, Environmental health perspectives.

[47]  J. de Mouzon,et al.  Declining sperm count , 1996, BMJ.

[48]  R M Sharpe,et al.  Declining sperm counts in men--is there an endocrine cause? , 1993, The Journal of endocrinology.

[49]  L. Hagmar,et al.  Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study , 2005, Environmental health : a global access science source.

[50]  P. Reddanna,et al.  Role of environmental estrogens in the deterioration of male factor fertility. , 2002, Fertility and sterility.

[51]  J. Fisher,et al.  Environmental anti-androgens and male reproductive health: focus on phthalates and testicular dysgenesis syndrome. , 2004, Reproduction.

[52]  L. Hagmar,et al.  Exposure to PCBs and p,p′-DDE and Human Sperm Chromatin Integrity , 2004, Environmental health perspectives.

[53]  S. Irvine,et al.  Evidence of deteriorating semen quality in the United Kingdom: birth cohort study in 577 men in Scotland over 11 years , 1996, BMJ.

[54]  L. Hagmar,et al.  Exposure to PCB and p, p'-DDE in European and Inuit populations: impact on human sperm chromatin integrity. , 2005, Human reproduction.

[55]  C. Ong,et al.  The associations among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. , 2003, Mutation research.

[56]  L. Hagmar,et al.  Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations , 2005, Environmental health : a global access science source.

[57]  D. Evenson,et al.  Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. , 2002, Journal of andrology.

[58]  D. Evenson,et al.  Environmental toxicants cause sperm DNA fragmentation as detected by the Sperm Chromatin Structure Assay (SCSA). , 2005, Toxicology and applied pharmacology.

[59]  D. Nebert,et al.  Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis. , 2000, Biochemical pharmacology.

[60]  L. Rienzi,et al.  Reduction of the incidence of sperm DNA fragmentation by oral antioxidant treatment. , 2005, Journal of andrology.

[61]  A. Agarwal,et al.  Role of reactive oxygen species in the pathophysiology of human reproduction. , 2003, Fertility and sterility.

[62]  T. Matsuda,et al.  Increasing incidence of testicular cancer worldwide: a review. , 2003, The Journal of urology.

[63]  S. Safe,et al.  Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action. , 2003, Chemical research in toxicology.

[64]  A. Giwercman,et al.  Relationships between sperm DNA fragmentation, sperm apoptotic markers and serum levels of CB-153 and p,p'-DDE in European and Inuit populations. , 2006, Reproduction.

[65]  J. Stephenson Breast Cancer Risk , 2003 .

[66]  Anne Marie Vinggaard,et al.  Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. , 2002, Toxicology and applied pharmacology.

[67]  A. Giwercman,et al.  Linkage between cryptorchidism, hypospadias, and GGN repeat length in the androgen receptor gene. , 2004, The Journal of clinical endocrinology and metabolism.

[68]  M. Spanô,et al.  The significance of sperm nuclear DNA strand breaks on reproductive outcome , 2005, Current opinion in obstetrics & gynecology.

[69]  A M Vinggaard,et al.  Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity. , 2001, Toxicology.

[70]  L. Rienzi,et al.  ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment , 2005 .