Maternal Exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin Results in Offspring Growth Retardation : Fetal Growth Hormone Supplementation Can Restore Bone Metabolism in Adulthood

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  • HATTORI Yukiko
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • TAKEDA Tomoki
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • YAMADA Hideyuki
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University
  • ISHII Yuji
    Laboratory of Molecular Life Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University Division of Pharmaceutical Cell Biology, Graduate School of Pharmaceutical Sciences, Kyushu University

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Other Title
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin母体暴露による胎児期成長ホルモン発現低下：胎児期の成長ホルモン補給による成長後の骨代謝改善
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin ボタイ バクロ ニ ヨル タイジ キセイチョウ ホルモン ハツゲン テイカ : タイジキ ノ セイチョウ ホルモン ホキュウ ニ ヨル セイチョウ ゴ ノ コツ タイシャ カイゼン

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Abstract

The direct supplementation of growth hormone (GH) to the fetus was previously shown to restore GH attenuations that result frommaternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Furthermore, it also stimulates the expression of insulin-like growth factor-1, which is a major growth factor that promotes systemic development, including body weight, body length, and learningmemory. In this study, a metabolomic analysis of serum in TCDD-exposed offspring reaching maturity was conducted. Elevated levels of activated vitamin D_3 were identified, and these were reduced to control levels with GH supplementation on gestational day 20. Inorganic phosphorus in the blood was similarly affected, but there was no change in calcium levels. The mRNA levels of cytochrome P450 (CYP) isoforms, CYP27B1 and CYP24A1 which are involved in activated vitamin D_3 production and inactivation, were not significantly changed. The results suggest that the TCDD-dependent elevation of 1a, 25- (OH)_2 vitamin D3 (1,25- (OH)_2D_3) in adulthood is due to factors other than the altered expression of synthetic and metabolic enzymes in the kidney. Bone-derived alkaline phosphatase (ALP) mRNA and serum ALP activity were significantly reduced by maternal TCDD exposure. Serum ALP was significantly improved by GH supplementation. The decrease in mononucleate cells around the osteoclasts in the tibia of male offspring after reaching maturity supported the results, and this tended to improve with fetal GH supplementation. TCDD was thus found to trigger a decrease in fetal GH levels and there were exceptionally high 1,25-(OH)_2D_3 levels when reaching maturity, which decreases the number of osteoblasts and suppresses bone formation.

Journal

  • 福岡醫學雜誌

    福岡醫學雜誌 114 (1), 51-64, 2023-03-25

    Fukuoka Medical Association

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