Rossi G L, Bestetti G E, Reymond M J, Lemarchand-Béraud T
Division of Experimental Pathology, University of Berne, Switzerland.
Exp Brain Res. 1991;83(2):349-56. doi: 10.1007/BF00231158.
Fetal exposure to cyproterone acetate (CPA), while allowing, normal sexual morphogenesis, has previously been shown to lead to functional endocrine abnormalities in adult rats of both sexes. Because of this, we examined morphologically and morphometrically the hypothalamic nuclei involved in sexual dimorphism as well as the pituitary lactotropes of rats exposed in utero from day 15 to 20 of gestation to CPA. Male and female offspring was studied at the age of 70-80 days. In both sexes the brain weight was lower (p less than 0.05) in CPA-treated than in control rats. Morphometrical investigations showed that the surface density (Sv) and the volume density (Vv) of the ventromedial nucleus were higher (p less than 0.05) in CPA-treated male than in control rats. By comparing sexes the Sv and Vv of the ventromedial nucleus were higher (p less than 0.01) in CPA-treated male than in corresponding female rats. Also the nuclear surface of the tyrosine hydroxylase-immunoreactive neurons of the arcuate nucleus was higher (p less than 0.05) in CPA-treated male than in female rats. In lactotropes of the pituitary gland the immunoreactive prolactin (PRL) was densitometrically increased (p less than 0.05) in CPA-treated female compared with control rats. By electron microscopy, PRL granules and autophagocytosis appeared to be more abundant in CPA-treated rats of both sexes. These data show that fetal exposure to CPA results in long-term anatomical and physiological alterations of hypothalamic and preoptic nuclei as well as of the pituitary lactotropes. These permanent changes support the functional endocrine abnormalities observed in adult rats.
胎儿暴露于醋酸环丙孕酮（CPA），虽能实现正常的性形态发生，但此前已表明会导致成年雌雄大鼠出现功能性内分泌异常。因此，我们对妊娠第15至20天子宫内暴露于CPA的大鼠，从形态学和形态计量学方面检查了参与性二态性的下丘脑核以及垂体催乳细胞。在70 - 80日龄时对雌雄后代进行了研究。与对照大鼠相比，经CPA处理的大鼠无论雌雄，脑重量均较低（p < 0.05）。形态计量学研究表明，经CPA处理的雄性大鼠腹内侧核的表面密度（Sv）和体积密度（Vv）高于对照大鼠（p < 0.05）。比较不同性别，经CPA处理的雄性大鼠腹内侧核的Sv和Vv高于相应的雌性大鼠（p < 0.01）。同样，经CPA处理的雄性大鼠弓状核酪氨酸羟化酶免疫反应性神经元的核表面积高于雌性大鼠（p < 0.05）。在垂体催乳细胞中，与对照大鼠相比，经CPA处理的雌性大鼠免疫反应性催乳素（PRL）的光密度增加（p < 0.05）。通过电子显微镜观察，经CPA处理的雌雄大鼠PRL颗粒和自噬现象似乎更为丰富。这些数据表明，胎儿暴露于CPA会导致下丘脑和视前核以及垂体催乳细胞出现长期的解剖学和生理学改变。这些永久性变化支持了在成年大鼠中观察到的功能性内分泌异常。
