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Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life

  • Developmental Toxicology
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Abstract

Two potential endocrine-disrupting chemicals, bisphenol A (BPA) and nonylphenol (NP), were assessed for their long-lasting effects on endocrine/reproductive systems following transplacental and lactational exposure to rat offspring during a time-window that included the critical period for brain sexual differentiation. Each chemical was mixed with diet at concentrations of 60, 600 and 3000 ppm and was provided to maternal Sprague-Dawley rats from gestational day (GD) 15 to postnatal day (PND) 10. Ethinylestradiol (EE) at 0.5 ppm was used as an estrogenic reference drug. During pregnancy and lactation, including the exposure period, a soy-free rodent diet was provided to eliminate possible modification of the study results by plant-derived phytoestrogens. Effects on endocrine/reproductive systems were evaluated by examining the anogenital distance, organ weights before puberty, onset of puberty, estrous cyclicity, and organ weights and histopathology of adult endocrine organs (at 11 weeks of age), as well as the volume of the sexually dimorphic nucleus of preoptic area. Both NP and BPA, at high doses, caused decreases in maternal body weights and retardation of offspring growth, but neither affected any of the endocrine/reproductive endpoints of offspring, whereas EE induced irreversible changes in estrous cyclicity and histopathology of ovaries and uterus of adult females. The results indicated that maternal dietary exposure to NP or BPA at concentrations up to 3000 ppm from GD 15 through PND 10 do not exert any apparent adverse effects on the endocrine/reproductive systems of offspring.

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Acknowledgements

This work was supported in part by Health and Labour Sciences Research Grants (Research on Food and Chemical Safety) from the Ministry of Health, Labour and Welfare of Japan.

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Authors and Affiliations

  1. Division of Pathology, National Institute of Health Sciences, 158-8501, Tokyo, Japan

    Hironori Takagi, Makoto Shibutani, Naoya Masutomi, Chikako Uneyama, Noriyuki Takahashi & Masao Hirose

  2. Pathogenetic Veterinary Science, United Graduate School of Veterinary Sciences, 501-1193, Gifu, Japan

    Hironori Takagi & Kunitoshi Mitsumori

  3. Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, 183-8509, Tokyo, Japan

    Kunitoshi Mitsumori

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  1. Hironori Takagi
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  2. Makoto Shibutani
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Correspondence to Makoto Shibutani.

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Takagi, H., Shibutani, M., Masutomi, N. et al. Lack of maternal dietary exposure effects of bisphenol A and nonylphenol during the critical period for brain sexual differentiation on the reproductive/endocrine systems in later life. Arch Toxicol 78, 97–105 (2004). https://doi.org/10.1007/s00204-003-0517-0

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  • DOI: https://doi.org/10.1007/s00204-003-0517-0

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