Funabashi Toshiya, Kawaguchi Maiko, Furuta Miyako, Fukushima Atsushi, Kimura Fukuko
Department of Physiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan.
Psychoneuroendocrinology. 2004 May;29(4):475-85. doi: 10.1016/s0306-4530(03)00055-6.
It has been suspected that endocrine disrupters induce abnormal differentiation and development of reproductive organs. In the present study, we examined whether exposure to bisphenol A (BPA), a known endocrine disrupter, during gestation and lactation affects sex difference in the number of corticotropin-releasing hormone-immunoreactive neurons (CRH neurons) in the preoptic area (POA) and the bed nucleus of the stria terminalis (BST). For that purpose, pregnant female Wistar rats (n=8-11 per treatment group) were treated with either 0.1% ethanol (control group) or 10 mg/l BPA (BPA group) dissolved in their drinking water until their offspring were weaned. In the control group, we confirmed a previous report that the POA of female rats contained significantly more CRH neurons than that of male rats (p<0.05). This significant sex difference was also evident in the BPA group, indicating that BPA exposure used in the present study had no effect on the sex difference in CRH neurons in the POA. We also found in the control group that the BST of female rats contained significantly more CRH neurons (p<0.05) than that of male rats. However, this significant sex difference was not observed in the BPA group (p>0.05), suggesting that BPA exposure affected the sex difference in CRH neurons in the BST. Since there was no statistically significant difference in the number of CRH neurons between the control and the BPA group, irrespective of the sex, the results suggested that a loss of sex difference in CRH neurons was due to both an increase in CRH neurons in male rats and a decrease in CRH neurons in female rats. The present study indicates that there is a significant sex difference in the number of CRH neurons in the BST as well as in the POA and that exposure to BPA during gestation and lactation causes a loss of this sex difference in the rat BST, but not in the POA. We suggest that CRH neurons in the BST are more susceptible to endocrine disrupters than those in the POA, irrespective of the sex.
人们怀疑内分泌干扰物会诱导生殖器官异常分化和发育。在本研究中，我们检测了在妊娠和哺乳期暴露于已知的内分泌干扰物双酚A（BPA）是否会影响视前区（POA）和终纹床核（BST）中促肾上腺皮质激素释放激素免疫反应性神经元（CRH神经元）数量的性别差异。为此，将怀孕的雌性Wistar大鼠（每个治疗组n = 8 - 11）用溶解于饮用水中的0.1%乙醇（对照组）或10 mg/l BPA（BPA组）进行处理，直至其后代断奶。在对照组中，我们证实了之前的报道，即雌性大鼠的POA中CRH神经元数量明显多于雄性大鼠（p<0.05）。这种显著的性别差异在BPA组中也很明显，表明本研究中使用的BPA暴露对POA中CRH神经元的性别差异没有影响。我们在对照组中还发现，雌性大鼠的BST中CRH神经元数量明显多于雄性大鼠（p<0.05）。然而，在BPA组中未观察到这种显著的性别差异（p>0.05），这表明BPA暴露影响了BST中CRH神经元的性别差异。由于无论性别如何，对照组和BPA组之间CRH神经元数量均无统计学显著差异，结果表明CRH神经元性别差异的丧失是由于雄性大鼠中CRH神经元增加以及雌性大鼠中CRH神经元减少所致。本研究表明，BST以及POA中CRH神经元数量存在显著的性别差异，并且在妊娠和哺乳期暴露于BPA会导致大鼠BST中这种性别差异丧失，但POA中未出现这种情况。我们认为，无论性别如何，BST中的CRH神经元比POA中的CRH神经元对内分泌干扰物更敏感。
