Progression of the Dose-Related Effects of Estrogenic Endocrine Disruptors, an Important Factor in Declining Fertility, Differs between the Hypothalamo-Pituitary Axis and Reproductive Organs of Male Mice

Journal of Veterinary Medical Science

Zhan-Peng YUE³  Chisato MORI⁴  Ken-ichiro MUTOH⁷  Shinji TSUKAHARA⁶  Nobuhiko HOSHI¹  Teruo SUGAWARA²  Yoshihisa HASEGAWA⁵  Hiroshi KITAGAWA¹  Katsuhiko WARITA¹ 

[1] Department of Bioresource and Agrobiosciences, Graduate School of Science and Technology, Kobe University;Department of Molecular Biochemistry, Graduate School of Medicine, Hokkaido University;Department of Histology and Embryology, Veterinary College, Jilin University;Department of Bioenvironmental Medicine, Graduate School of Medicine, Chiba University;Department of Experimental Animal Science, School of Veterinary Medicine and Animal Sciences, Kitasato University;Division of Environmental Health Sciences, National Institute for Environmental Studies;Department of Veterinary Anatomy, School of Veterinary Medicine and Animal Sciences, Kitasato University

关键词: diethylstilbestrol (DES);    endocrine disruptors;    fertility rate;    fetal and/or neonatal exposure;    steroidogenic acute regulatory protein (StAR);   

DOI  :  10.1292/jvms.68.1257

学科分类：兽医学

来源: Japanese Society of Veterinary Science

【 摘 要 】

References(40)Cited-By(12)For the purpose of investigation of working mechanisms in endocrine disruptors, we evaluated the dose-related effects of fetal and/or neonatal exposure to an estrogenic compound on the male reproductive organs in adult mice, particularly with respect to gene expression of steroidogenic acute regulatory protein (StAR). The pregnant ICR mice were given subcutaneous injections of 10 μg/day/animal of diethylstilbestrol (DES) to subject the fetal mice to in utero exposure (IUE). Subsequently, the newborn male mice were subjected to neonatal exposure (NE) by treatment with vehicle or 0.1-10 μg/day/animal of DES. Fertility rates of each group were as follows: control, 100%; IUE only, 60%; IUE+NE 0.1 μg, 25%; IUE+NE 1 μg, 0%; IUE+NE 10 μg, 0%. In general histology, germ cell layers in the seminiferous tubules were thinned in the group of IUE+NE 10 μg. Hypoplasia of the Leydig cells, in which the staining intensity of eosin was diminished, was also observed in the groups of IUE+NE 0.1-10 μg. The androgen receptor (AR) and estrogen receptor alpha (ERα) immunoexpression in the Leydig cells of IUE+NE 1-10 μg was slightly lower than that in the controls. Long-term dysfunction of the hypothalamo-pituitary-testicular axis, including sustained hypoproduction of gonadotropin and testosterone, and altered expressions of steroid hormone receptors and StAR genes were observed. The hypothalamo-pituitary control of gonadotropin secretion may be affected by the smaller doses of estrogenic agents than the reproductive organs. Furthermore, the fertility rate in the male mice exposed to this estrogenic agent was closely correlated with the testosterone levels, and even more so with the rate-limiting factor of steroidogenesis, StAR. This finding suggests that endocrine disruptors have an important pronounced effect on StAR gene expression.

【 授权许可】

Unknown