4.2 Review

Hypothesis: Estrogen Related Thrombosis Explains the Pathogenesis and Epidemiology of Gastroschisis

期刊

AMERICAN JOURNAL OF MEDICAL GENETICS PART A
卷 158A, 期 4, 页码 808-811

出版社

WILEY
DOI: 10.1002/ajmg.a.35203

关键词

gastroschisis; maternal age; race; body mass index; estrogen; thrombosis; atrazine; palmitic acid; limb-body wall complex

向作者/读者索取更多资源

A three-part hypothesis is proposed to explain the unusual epidemiology of gastroschisis, a congenital abnormality of the abdominal wall, which has a rising frequency, a higher rate in first and young mothers in whites but not blacks, and a unique negative correlation with obesity. The hypothesis involves: (1) An early estrogenic thrombophilia, (2) racial differences in thrombosis, and (3) thrombotic by-products interfering with early developmental signaling. For the first: (1) An estrogenic thrombophilia is a known effect. (2) A mouse model links excess estrogen to thromboses affecting the fetus. (3) Young and first mothers have higher first trimester estrogen levels. (4) A negative correlation between body mass index and pregnancy estradiol accounts for the weight relationship. (5) Maternal alcohol raises estrogen levels in premenopausal women. (6) A link with atrazine, an estrogenic endocrine disruptor, has been found, and rising frequencies of gastroschisis make this and other such chemicals a particular concern if estrogen is indeed involved. For the second: Blacks have a different thrombophilic gene background and less of a thrombotic response to estrogen than whites, explaining racial differences. For the third: Protein palmitoylation affects cell signaling in development, and lipid rafts, a major aspect of thromboses, facilitate this process. Such thrombotic by products could be the source of palmitic acid rich amniotic vacuoles with gastroschisis. Similar vacuoles can occur with limb-body wall defects, another early developmental anomaly associated with decreased maternal age that may have a similar pathogenesis. Later thrombotic related anomalies with a similar epidemiology seem to primarily involve vascular disruptions, but localized signaling anomalies may also occur. (C) 2012 Wiley Periodicals, Inc.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.2
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据