title: Hypothesis: Estrogen related thrombosis explains the pathogenesis and epidemiology of gastroschisis.
abstract: 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 byproducts 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.
authors.affiliation: mlubinsky@wi.rr.com
authors.forename: Mark
authors.initials: M
authors.lastname: Lubinsky
mesh_terms: D034861:Abdominal Wall / Q000002:abnormalities; D000428:Alcohol Drinking; D000818:Animals; D001280:Atrazine / Q000008:administration & dosage; D015992:Body Mass Index; D004967:Estrogens / Q000097:blood / Q000378:metabolism*; D005260:Female; D020139:Gastroschisis / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D006801:Humans; D008423:Maternal Age; D051379:Mice; D019308:Palmitic Acid; D011247:Pregnancy; D044469:Racial Groups; D013927:Thrombosis / Q000473:pathology*
chemical_list: D004967:Estrogens; D019308:Palmitic Acid; D001280:Atrazine