Skip to main content
SpringerLink
Log in

Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the body burden in offspring of long-evans rats

  • Original Article
  • Published:
Environmental Health and Preventive Medicine Aims and scope

Abstract

Objectives

In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) results in a wide variety of developmental effects in pups at doses much lower than those causing overt toxicity in adult animals. We investigated the relationship between tissue concentrations of TCDD in dams and fetuses and developmental effects on pups.

Materials and Methods

Pregnant Long-Evans rats were given TCDD at a single oral dose of 12.5, 50, 200, or 800 ng of TCDD or [3H]-TCDD/kg bw on gestation day (GD) 15. Dams were sacrificed on GD16 and GD21, and the tissue concentrations of TCDD were measured in dams and fetuses. Pups were sacrificed on postnatal day (PND) 49 and PND63 for males and PND70 for females, and the reproductive effects and tissue concentrations of TCDD were determined.

Results

The sex ratio (male/female) on GD21 was significantly reduced at 50 ng TCDD/kg and at 12.5 and 50 ng TCDD/kg at birth, but not at other doses. Delayed puberty was observed in males at 200 ng TCDD/kg and in males and females at 800 ng TCDD/kg. Anogenital distance, testis weight, epididymal sperm count, sperm motility, and ejaculated sperm count were not affected. Estrous cyclicity was not different from that of the control in any treatment group. A dose-dependent decrease in weight of seminal vesicle and prostate on PND49 was observed. Prostate weight was significantly decreased at 800 ng TCDD/kg. At this dose, maternal body burden and TCDD concentration in fetuses were 290 pg TCDD/g and 52 pg TCDD/g on GD16, respectively.

Reduced prostate weight is a sensitive and commonly observed endpoint so that the body burdens of dams and fetuses at the LOAEL of this endpoint could be served as the basis for establishing TDI for dioxins.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yonemoto J. The effects of dioxin on reproduction and development Ind Health. 2000; 38: 259–268.

    Article  PubMed  CAS  Google Scholar 

  2. Birnbaum L. Developmental effects of dioxins and related endocrine disrupting chemicals. Toxicol Lett. 1995; 82/83: 743–750.

    Article  CAS  Google Scholar 

  3. Tohyama C. Low-dose exposure to dioxin, its toxicities and health risk assessment (ES493). Environmental Sci. 2002; 9: 37–50.

    CAS  Google Scholar 

  4. Schecter A, Gasiewitz T, editors, Dioxins and Health. John Wiley & Sons Inc, 2003.

  5. van Leeuwen FX, Feelev M, Schrenk D, Larsen JC, Farland W, Younes M. Dioxins: WHO’s tolerable daily intake (TDI) revisited. Chemosphere. 2000; 40: 1095–1101.

    Article  PubMed  Google Scholar 

  6. WHO, Consultation on tolerable daily intake from food of PCDDs and PCDFs, WHO regional office for Europe, 1991.

  7. Mably TA, Moore RW, Peterson RE.In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: 1. Effects on androgenic status. Toxicol Appl Pharmacol. 1992; 114: 97–107.

    Article  PubMed  CAS  Google Scholar 

  8. Mably TA, Moore RW, Goy RW, Peterson RE.In utero and lactational exposure of male rats to 2,3,7,8-tetrachloro-dibenzo-p-dioxin: 2. Effects on sexual behevior and the regulation of lutenizing hormone secretion in adulthood. Toxicol Appl Pharmacol. 1992; 114: 108–117.

    Article  PubMed  CAS  Google Scholar 

  9. Mably TA, Bierke DL, Moore RW, Gendron-Fitzpatrick A, Peterson RE.In utero and lactational exposure of male rats to 2,3,7,8-tetrachlorodibenzo-p-dioxin: 3. Effects on spermatogenesis and reproductive capability. Toxicol Appl Pharmacol. 1992; 114: 118–126.

    Article  PubMed  CAS  Google Scholar 

  10. Gray LEJ, Ostby JS, Kelce WR. 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. Toxicol Appl Phamacol. 1997; 146: 11–20.

    Article  CAS  Google Scholar 

  11. Ohsako S, Miyabara Y, Nishimura N, Kurosawa S, Sakaue M, Ishimura R, Sato M, Takeda K, Aoki Y, Sone H, Tohyama C, Yonemoto J. Maternal exposure to a low dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) suppressed the development of reproductive organs of male rats: Dose-dependent increase of mRNA levels of 5α-reductase type 2 in contrast to decrease of androgen receptor in the pubertal ventral prostate. Toxicol Sci. 2001; 60: 132–143.

    Article  PubMed  CAS  Google Scholar 

  12. Hurst CH, DeVito MJ, Setzer RW, Birnbaum LS. Acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in pregnant Long Evans rats: Association of measured tissue concentrations with developmental effects. Toxicol Sci. 2000; 53: 411–420.

    Article  PubMed  CAS  Google Scholar 

  13. Ohsako S, Miyabara Y, Sakaue M, Ishimura R, Kakeyama M, Izumi H, Yonemoto J, Tohyama C. Developmental stage-specific effects of perinatal 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on reproductive organs of male rat offspring. Toxicol Sci. 2002; 66: 283–292.

    Article  PubMed  CAS  Google Scholar 

  14. Simanainen U, Haavisto T, Tuomisto JT, Paranko J, Toppari J, Tuomisto J, Peterson RE, Viluksela M. Pattern of male reproductive system effects after in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in three differentially TCDD-sensitive rat lines. Toxicol Sci. 2004; 80: 101–108.

    Article  PubMed  CAS  Google Scholar 

  15. Jana NR, Sarkar S, Yonemoto J, Tohyama C, Sone H. Strain differences in cytochrome P4501A1 gene expression caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver: Role of the aryl hydrocarbon receptor and its nuclear translocator. Biochem Biophys Res Commun. 1998; 248: 554–559.

    Article  PubMed  CAS  Google Scholar 

  16. Gray LEJ, Wolf C, Mann P, Ostby JS.In utero exposure to low doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin alters reproductive development of female Long Evans hooded rat offspring. Toxicol Appl Pharmacol. 1997; 146: 237–244.

    Article  PubMed  CAS  Google Scholar 

  17. Ikeda M.In Final Report of Core Research for Evolutional Science and Technology (Endocrine Disruptor) (FY1999–2003), Kawaguchi, Japan: Japan Science and Technology Agency, 2004. (in Japanese)

    Google Scholar 

  18. Kakeyama M.In Final Report of Core Research for Evolutional Science and Technology (Endocrine Disruptor) (FY1999–2003), Kawaguchi, Japan: Japan Science and Technology Agency, 2004. (in Japanese)

    Google Scholar 

  19. Mocarelli P, Brambilla P, Gerthoux P, Patterson D, Needham L. Change in sex ratio with exposure to dioxin [letter]. Lancet. 1996; 348: 409.

    Article  PubMed  CAS  Google Scholar 

  20. vom Saal FS, Timms BG, Montano MM, Palanza P, Thayer KA, Nagel SC, et al. 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. 1997; 94: 2056–2061.

    Article  Google Scholar 

  21. Markowski VP, Zareba G, Stern S, Cox C, Weiss B. Altered operant responding for motor reinforcement and the determination of benchmark doses following perinatal exposure to low-level 2,3,7,8-tetrachlorodibenzo-p-dioxin. Environ Health Perspect. 2001; 109: 621–627.

    Article  PubMed  CAS  Google Scholar 

  22. Hojo R, Stern S, Zareba G, Markowski VP, Cox X, Kost JT, Weiss B. Sexually dimorphic behavioral responses to prenatal dioxin exposure. Environ Health Perspect. 2002; 110: 247–254.

    PubMed  CAS  Google Scholar 

  23. Abraham K, Krowke R, Neubert D. Pharmacokinetics and biological activity of 2,3,7,8-tetrachlorodibenzo-p-dioxin: 1. Dose-dependent tissue distribution and induction of hepatic ethoxyresorfin O-deethylase in rats following a single injection. Arch Toxicol. 1988; 62: 359–368.

    Article  PubMed  CAS  Google Scholar 

  24. Diliberto JJ, Burgin DE, Birnbaum LS. Role of CYP1A2 in hepatic sequestration of dioxin: Studies using CYP1A2 knock-put mice. Biochem Biophys Res Commun. 1997; 236: 431–433.

    Article  PubMed  CAS  Google Scholar 

  25. Diliberto JJ, Burgin DE, Birnbaum LS. Effects of CYP1A2 on disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 2,3,7,8-pentachlorodibenzofuran, and 2,2′,4,4′,5,5′-hexachlorobiphenyl in CYP1A2 knockout and parental (C57BL/6N and 129/Sv) strains of mice. Toxicol Appl Pharmacol. 1999; 159: 52–64.

    Article  PubMed  CAS  Google Scholar 

  26. Roman B, Timms B, Prins G, Peterson R.In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 2. Effects on growth and cytodifferentiation. Toxicol Appl Phamacol. 1998; 150: 254–270.

    Article  CAS  Google Scholar 

  27. Roman B, Peterson R.In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. 1. Effects on gene expression. Toxicol Appl Pharmacol. 1998; 150: 240–253.

    Article  PubMed  CAS  Google Scholar 

  28. Theobald H, Roman B, Lin T, Ohtani S, Chen S, Peterson R, 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits luminal cell differentiation and androgen responsiveness of the ventral prostate without inhibiting prostatic 5alpha-dihydrotestosterone formation or testicular androgen production in rat offspring Toxicol Sci. 2000; 58: 324–338.

    Article  PubMed  CAS  Google Scholar 

  29. Lin T, Ko K, Moore R, Simanainen U, Oberley T, Peterson R. Effects of aryl hydrocarbon receptor null mutation andin utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure on prostate and seminal vesicle development in C57BL/6 mice. Toxicol Sci. 2002; 68: 479–487.

    Article  PubMed  CAS  Google Scholar 

  30. Ko K, Theobald H, Peterson R.In utero and lactational exposure of the male rat to 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs prostate development. Toxicol Sci. 2002; 70: 227–237.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Author notes

  1. Tutomu Ichiki

    Present address: Safety Assessment Laboratory, Material Evaluation Center, Dainippon Ink and Chemicals, Inc., Sakura, Japan

Authors and Affiliations

  1. Health Effects Research Team, Endocrine Disruptors & Dioxin Research Project, National Institute for Environmental Studies, 16-2 Onogawa, 805-8506, Tsukuba, Japan

    Junzo Yonemoto & Chiharu Tohyama

  2. Panapharm Laboratories Inc., Uto, Japan

    Tutomu Ichiki

  3. Ministry of the Environment, Tokyo, Japan

    Teiji Takei

Authors
  1. Junzo Yonemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tutomu Ichiki
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Teiji Takei
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chiharu Tohyama
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Junzo Yonemoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yonemoto, J., Ichiki, T., Takei, T. et al. Maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin and the body burden in offspring of long-evans rats. Environ Health Prev Med 10, 21–32 (2005). https://doi.org/10.1265/ehpm.10.21

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1265/ehpm.10.21

Key words

Search

Navigation