Three-generation experiment showed female C57BL/6J mice drink drainage canal water containing low level of TCDD-like activity causing high pup mortality.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), polychlorinated biphenyls (PCBs) and similar compounds are toxic to animals and humans. Based on a yeast reporter system, AhR-activating ligands similar in concentration to 2 ng/l of TCDD were detected in two canal waters in Guangzhou, China. In this study, a three-generation experiment was conducted to assess the reproductive and developmental risks associated with these waters in C57BL/6J female mice, including female reproduction, pup indices, reproductive hormone levels, and levels of AhR, ARNT, and CYP1A2 in the uterus. Similar reproductive toxic effects were produced in the offspring of mice that drank the canal water as would occur if they drank 2 ng/l/day TCDD. The major reproductive indices that were affected included mating time and gestation length over all the generations. A striking finding is the TCDD (2 ng/l) and the water samples significantly reduced Day 4 pup survival rates in the F2 and F3. Both TCDD exposure and drinking canal water decreased estradiol-17β (E2) levels in the multiparous females and decreased follicle-stimulating hormone (FSH), luteinizing hormone (LH) and E2 levels in the virgin females. Immunochemical staining revealed that the AhR and CYP1A2 positive signals were enhanced, and the ARNT positive signal was weakened in the uteri of mice drinking water with TCDD (2 ng/l) and the canal water samples. These results imply that the canal water contains AhR ligands that could induce similar toxic effects as do low levels of TCDD. Exposure to these contaminants can significantly impair the reproductive health of female mice. Considering this canals are open directly to Pearl River, whether these effects could be caused in human reproduction and development warrants further study.

[1]  Y. Ishii,et al.  [The effect of maternal exposure to dioxin on fetal steroidogenesis in the steroidogenic organs]. , 2011, Fukuoka igaku zasshi = Hukuoka acta medica.

[2]  H. Wariishi,et al.  Maternal exposure to dioxin reduces hypothalamic but not pituitary metabolome in fetal rats: a possible mechanism for a fetus-specific reduction in steroidogenesis. , 2010, The Journal of toxicological sciences.

[3]  L. Birnbaum,et al.  The effect of dose on 2,3,7,8-TCDD tissue distribution, metabolism and elimination in CYP1A2 (-/-) knockout and C57BL/6N parental strains of mice. , 2009, Toxicology and applied pharmacology.

[4]  W. Heideman,et al.  Persistent adverse effects on health and reproduction caused by exposure of zebrafish to 2,3,7,8-tetrachlorodibenzo-p-dioxin during early development and gonad differentiation. , 2009, Toxicological sciences : an official journal of the Society of Toxicology.

[5]  M. Kakeyama,et al.  Perinatal exposure of female rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin induces central precocious puberty in the offspring. , 2008, The Journal of endocrinology.

[6]  C. Struble,et al.  Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity. , 2008, Reproductive toxicology.

[7]  K. Hayes,et al.  Hepatic transcriptional networks induced by exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 2007, Chemical research in toxicology.

[8]  J. Tuomisto,et al.  Differences in acute toxicity syndromes of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin in rats. , 2007, Toxicology.

[9]  J. Olson,et al.  Comparative developmental toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin in the hamster, rat and guinea pig. , 2007, Toxicology.

[10]  K. Bock,et al.  Ah receptor: dioxin-mediated toxic responses as hints to deregulated physiologic functions. , 2006, Biochemical pharmacology.

[11]  Bing Li,et al.  The early embryo loss caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin may be related to the accumulation of this compound in the uterus. , 2006, Reproductive toxicology.

[12]  J. Toppari,et al.  In utero and lactational exposure to TCDD; steroidogenic outcomes differ in male and female rat pups. , 2005, Toxicological sciences : an official journal of the Society of Toxicology.

[13]  Masayuki Yamamoto,et al.  Intrinsic Function of the Aryl Hydrocarbon (Dioxin) Receptor as a Key Factor in Female Reproduction , 2005, Molecular and Cellular Biology.

[14]  R. Parker.  Testing for Reproductive Toxicity , 2005 .

[15]  Huangjin Li.  UTILIZATION OF YEAST GENE REPORT SYSTEM TO DETECT ENVIRONMENTAL DIOXINS-LIKE SUBSTANCES , 2004 .

[16]  M. Wierman,et al.  2,3,7,8-Tetrachlorodibenzo-p-Dioxin (TCDD) Stimulates Gonadotropin Secretion in the Immature Female Sprague-Dawley Rat Through a Pentobarbital- and Estradiol-Sensitive Mechanism but Does Not Alter Gonadotropin-Releasing Hormone (GnRH) Secretion by Immortalized GnRH Neurons In Vitro1 , 2003, Biology of reproduction.

[17]  C. Tohyama,et al.  Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  J. Overstreet,et al.  Molecular target of endocrine disruption in human luteinizing granulosa cells by 2,3,7,8-tetrachlorodibenzo-p-dioxin: inhibition of estradiol secretion due to decreased 17alpha-hydroxylase/17,20-lyase cytochrome P450 expression. , 2003, Endocrinology.

[19]  L. Birnbaum,et al.  Persistent abnormalities in the rat mammary gland following gestational and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  E. Gregoraszczuk.  Dioxin exposure and porcine reproductive hormonal activity. , 2002, Cadernos de saude publica.

[21]  A. Okey,et al.  Persistent, low-dose 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: effect on aryl hydrocarbon receptor expression in a dioxin-resistance model. , 2001, Toxicology and applied pharmacology.

[22]  M. DeVito,et al.  Tissue disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in maternal and developing long-evans rats following subchronic exposure. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  P. Terranova,et al.  Gonadotropin-releasing hormone (GnRH) partially reverses the inhibitory effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on ovulation in the immature gonadotropin-treated rat. , 2000, Toxicology.

[24]  L. Birnbaum,et al.  Non-carcinogenic effects of TCDD in animals , 2000, Food additives and contaminants.

[25]  J. Overstreet,et al.  2,3,7,8-Tetrachlorodibenzo-p-Dioxin Decreases Estradiol Production Without Altering the Enzyme Activity of Cytochrome P450 Aromatase of Human Luteinized Granulosa Cells In Vitro1 , 2000, Biology of reproduction.

[26]  C. Miller.  A human aryl hydrocarbon receptor signaling pathway constructed in yeast displays additive responses to ligand mixtures. , 1999, Toxicology and applied pharmacology.

[27]  L. Gray,et al.  Gestational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) severely alters reproductive function of female hamster offspring. , 1999, Toxicological sciences : an official journal of the Society of Toxicology.

[28]  J. Overstreet,et al.  Endocrine biomarkers of early fetal loss in cynomolgus macaques (Macaca fascicularis) following exposure to dioxin. , 1999, Biology of reproduction.

[29]  R. Hutz,et al.  Dioxin perturbs, in a dose- and time-dependent fashion, steroid secretion, and induces apoptosis of human luteinized granulosa cells. , 1998, Endocrinology.

[30]  G. Lucier,et al.  Animal models of human response to dioxins. , 1998, Environmental health perspectives.

[31]  L. Gray,et al.  A dose-response analysis of the reproductive effects of a single gestational dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male Long Evans Hooded rat offspring. , 1997, Toxicology and applied pharmacology.

[32]  C. Chaffin,et al.  Alterations to the pituitary-gonadal axis in the peripubertal female rat exposed in utero and through lactation to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1997, Biology of Reproduction.

[33]  L. Birnbaum,et al.  Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on influenza virus host resistance in mice. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[34]  D. Johnson,et al.  Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on estrous cyclicity and ovulation in female Sprague-Dawley rats. , 1995, Toxicology letters.

[35]  M. Hadders‐Algra,et al.  Perinatal exposure to polychlorinated biphenyls and dioxins and its effect on neonatal neurological development. , 1995, Early human development.

[36]  S. Safe,et al.  Modulation of gene expression and endocrine response pathways by 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds. , 1995, Pharmacology & therapeutics.

[37]  O. Hankinson.  The aryl hydrocarbon receptor complex. , 1995, Annual review of pharmacology and toxicology.

[38]  L. Birnbaum.  The mechanism of dioxin toxicity: relationship to risk assessment. , 1994, Environmental health perspectives.

[39]  S. Safe,et al.  Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. , 1994, Critical reviews in toxicology.

[40]  W. Dmowski,et al.  Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. , 1993, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[41]  D. Morris,et al.  A review of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced changes in immunocompetence: 1991 update. , 1991, Toxicology.

[42]  L S Birnbaum,et al.  A critical review of the developmental toxicity and teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: recent advances toward understanding the mechanism. , 1990, Teratology.

[43]  S. Schantz,et al.  Learning in monkeys exposed perinatally to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). , 1989, Neurotoxicology and teratology.

[44]  F A Smith,et al.  Three-generation reproduction study of rats given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet. , 1979, Toxicology and applied pharmacology.