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We therefore examined the effect of sFlt\u20101 on placental morphology and physiology at embryonic day 18.5 with histologic and morphometric analyses, transcript analyses, immunoblotting, and methylation studies. Interestingly, placental overexpression of sFlt\u20101 leads to IUGR in the fetus and results in lower placental weights. Moreover, we observed altered trophoblast differentiation with reduced expression of IGF2, resulting in a smaller placenta, a smaller labyrinth, and the loss of glycogen cells in the junctional zone. Changes in IGF2 are accompanied by small changes in its DNA methylation, whereas overall DNA methylation is unaffected. In addition, the expression of placental nutrient transporters, such as the glucose diffusion channel Cx26, is decreased. In contrast, the expression of the fatty acid transporter CD36 and the cholesterol transporter ABCA1 is significantly increased. In conclusion, placental sFlt\u20101 overexpression resulted in a reduction in the differentiation of the spongiotrophoblast into glycogen cells. These findings of a reduced exchange area of the labyrinth and glycogen stores, as well as decreased expression of glucose transporter, could contribute to the intrauterine growth restriction phenotype. All of these factors change the intrauterine availability of nutrients. Thus, we speculate that the alterations triggered by increased anti\u2010angiogenesis strongly affect fetal outcome and programming. J. Cell. Biochem. 118: 1316\u20131329, 2017. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcb.25789","type":"journal-article","created":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T04:04:18Z","timestamp":1478750658000},"page":"1316-1329","source":"Crossref","is-referenced-by-count":42,"title":["Placental\u2010Specific Overexpression of sFlt\u20101 Alters Trophoblast Differentiation and Nutrient Transporter Expression in an IUGR Mouse Model"],"prefix":"10.1002","volume":"118","author":[{"given":"Elisabeth","family":"K\u00fchnel","sequence":"first","affiliation":[{"name":"Department of Gynecology and Obstetrics University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Kleff","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology University of Duisburg\u2010Essen Essen 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