TRANSPLACENTAL UPTAKE OF GLUCOSE IS DECREASED IN EMBRYONIC LETHAL CONNEXIN26-DEFICIENT MICE

Mice that harbor a targeted homozygous defect in the gene coding for t he gap junctional protein connexin26 died in utero during the transien t phase from early to midgestation, From day 10 post coitum onwards, d evelopment of homozygous embryos was retarded, which led to death arou nd day 11 post coitum. Except for growth retardation, no gross morphol ogical alterations were detected between homozygous connexin26-defecti ve embryos and wild-type littermates. At day 9 postcoitum, when chorio allantoic placenta started to function, connexin26 was weakly expresse d in the yolk sac epithelium, between syncytiotrophoblasts I and II in the labyrinth region of the placenta, and in the skin of the embryo. At day 10 post coitum, expression of connexin26 in the placenta was mu ch stronger than at the other locations, To analyze involvement of con nexin26 in the placental transfer of nutrients, we have measured embry onic uptake of the nonmetabolizable glucose analogue 3-O-[C-14]methylg lucose, injected into the maternal tail vein. At day 10 post coitum, v iable, homozygous connexin26-defective embryos accumulated only simila r to 40% of the radioactivity measured in wild-type and heterozygous l ittermates of the same size. We conclude that the uptake of glucose, a nd presumably other nutrients as well, from maternal blood into connex in26-deficient mouse embryos was severely impaired and apparently not sufficient to support the rapid organogenesis during midgestation. Our results suggest that connexin26 gap junction channels likely fulfill an essential role in the transfer of maternal nutrients and embryonic waste products between syncytiotrophoblast I and II in the labyrinth l ayer of the mouse placenta.