Maternal exposure to dioxin reduces hypothalamic but not pituitary metabolome in fetal rats: a possible mechanism for a fetus-specific reduction in steroidogenesis

• DOI: 10.2131/jts.35.365
• Publication Date: 2010-06-01T06:06:58Z
• Authors: Yuki Matsumoto; Takumi Ishida; Tomoki Takeda; Takayuki Koga; Misaki Fujii; Yuji Ishii; Yoshinori Fujimura; Daisuke Miura; Hiroyuki Wariishi; Hideyuki Yamada
• Keywords: Male; 0301 basic medicine; Polychlorinated Dibenzodioxins; Glutamine; Hypothalamus; Gas Chromatography-Mass Spectrometry; Rats; 3. Good health; 03 medical and health sciences; Maternal Exposure; Pregnancy; Depression, Chemical; Pituitary Gland; Metabolome; Animals; Female; Rats, Wistar; Maternal-Fetal Exchange; Gonadotropins; gamma-Aminobutyric Acid

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) reduces the synthesis of pituitary gonadotropins in a fetal age-specific manner. The pituitary synthesis of gonadotropins is regulated by the hypothalamus and, thus, needs the differentiation and development of the hypothalamus requiring a number of factors including energy supply and neurotransmitters. To investigate the mechanism whereby TCDD reduces fetal gonadotropins, we carried out a comparative study on the metabolomes of the hypothalamus and pituitary using fetal and mature Wistar rats. Male fetuses at gestational day (GD)20 were removed from dams treated orally with TCDD (1 microg/kg) at GD15, and the metabolome profiles were analyzed by gas chromatography-mass spectrometry (GC-MS). The principal component analysis of GC-MS data revealed that TCDD caused a change in the profile of fetal metabolome more markedly in the hypothalamus than in the pituitary. In sharp contrast, TCDD did not cause any marked alteration in hypothalamic as well as pituitary metabolomes in male rats born of untreated dams and treated with TCDD at postnatal day 49. It was also demonstrated that a number of fetal hypothalamic components, including glutamine and gamma-aminobutyric acid, are reduced by TCDD. These results demonstrate a possibility that TCDD may reduce the metabolic activity of the hypothalamus in a fetus-specific fashion, resulting in the reduced synthesis of gonadotropins.