کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2595558 1562335 2014 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Effects of tamoxifen on the sex determination gene and the activation of sex reversal in the developing gonad of mice
ترجمه فارسی عنوان
اثرات تاموکسیفن بر ژن تعیین جنسیت و فعال شدن جنبش در گوناد در حال رشد موش
کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی


• Evaluating sex determination pathway by in vivo and in vitro assay.
• Changes in the expression of sex determination genes caused by TAM in mammals.
• TAM affects SOX9 and FOXL2 signaling pathway and results in partial sex reversal.
• The effect of TAM is relevant to the human gender imbalance.

Tamoxifen, as well as most endocrine-disrupting chemicals, affects the reproductive system and sexual development, but little is known about its disruption of the molecular pathways regulating mammalian sex determination. In fetal mice, the expression levels and pattern of key genes involved in controlling sexually dimorphic balance were analyzed both in vivo and in vitro by using whole-mount in situ hybridization and quantitative-PCR. Developmental tamoxifen exposure induced abnormal up-regulation of the testis differentiation marker Pdfgra in Leydig cells and of Sox9 and Fgf9 in Sertoli cells in XX gonad. Immunohistochemistry analysis confirmed the over-expression of SOX9 protein. Accordingly, the ovary development marker Foxl2 was depressed at both the mRNA and protein levels. The increase in testosterone and the reduction in 17β-estradiol and progesterone were observed by using the in vitro assay with organotypic cultures. Taken together, results indicated that tamoxifen induced the ectopic expression of well-established sex-specific genes during the critical developmental period, thus resulting in abnormal testicular development in the XX gonad of mammals. This study facilitates a better understanding of the molecular mechanisms of antiestrogens and possibly of compounds that interrupt estrogen signaling by other modes of action, and the association with the pathogenesis of human sexual developmental disorders.

Figure optionsDownload as PowerPoint slide

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 321, 3 July 2014, Pages 89–95
نویسندگان
, , , , , , , , ,