{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:28:22Z","timestamp":1791325702628,"version":"4.3.1"},"reference-count":34,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,1,14]],"date-time":"2014-01-14T00:00:00Z","timestamp":1389657600000},"content-version":"vor","delay-in-days":13,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diabetes Metabolism Res"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Adenosine monophosphate\u2010activated protein kinase (AMPK) is stimulated in embryos during diabetic pregnancy by maternal hyperglycaemia\u2010induced embryo oxidative stress. Stimulation of AMPK disrupts embryo gene expression and causes neural tube defects. Metformin, which may be taken during early pregnancy, has been reported to stimulate AMPK activity. Thus, the benefits of improved glycaemic control could be offset by stimulated embryo AMPK activity. Here, we investigated whether metformin can stimulate AMPK activity in mouse embryos and can adversely affect embryo gene expression and neural tube defects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Pregnant nondiabetic mice were administered metformin beginning on the first day of pregnancy. Activation of maternal and embryo AMPK [phospho\u2010AMPK <jats:italic>\u03b1<\/jats:italic> (Thr172) relative to total AMPK], expression of <jats:italic>Pax3<\/jats:italic>, a gene required for neural tube closure, and neural tube defects were studied. Mouse embryonic stem cells were used as a cell culture model of embryonic neuroepithelium to study metformin effects on AMPK and <jats:italic>Pax3<\/jats:italic> expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Metformin had no effect on AMPK in embryos or maternal skeletal muscle but increased activated AMPK in maternal liver. Metformin did not inhibit <jats:italic>Pax3<\/jats:italic> expression or increase neural tube defects. However, metformin increased activated AMPK and inhibited <jats:italic>Pax3<\/jats:italic> expression by mouse embryonic stem cells. <jats:italic>Mate1<\/jats:italic>\/<jats:italic>Slc47a1<\/jats:italic> and <jats:italic>Oct3<\/jats:italic>\/<jats:italic>Slc22a<\/jats:italic>, which encode metformin transporters, were expressed at barely detectable levels by embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Although metformin can have effects associated with diabetic embryopathy <jats:italic>in vitro<\/jats:italic>, the lack of effects on mouse embryos <jats:italic>in vivo<\/jats:italic> may be due to lack of metformin transporters and indicates that the benefits of metformin on glycaemic control are not counteracted by stimulation of embryo AMPK activity and consequent embryopathy. 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