Transplacental uptake of glucose is decreased in embryonic lethal connexin26-deficient mice.
Mice that harbor a targeted homozygous defect in the gene coding for the gap junctional protein connexin26 died in utero during the transient phase from early to midgestation. From day 10 post coitum onwards, development of homozygous embryos was retarded, which led to death around day 11 post coitum. Except for growth retardation, no gross morphological alterations were detected between homozygous connexin26-defective embryos and wild-type littermates. At day 9 postcoitum, when chorioallantoic placenta started to function, connexin26 was weakly expressed 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 much stronger than at the other locations. To analyze involvement of connexin26 in the placental transfer of nutrients, we have measured embryonic uptake of the nonmetabolizable glucose analogue 3-O-[14C]methylglucose, injected into the maternal tail vein. At day 10 post coitum, viable, homozygous connexin26-defective embryos accumulated only approximately 40% of the radioactivity measured in wild-type and heterozygous littermates of the same size. We conclude that the uptake of glucose, and presumably other nutrients as well, from maternal blood into connexin26-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 layer of the mouse placenta.
Gabriel
H D
HD
Institut für Genetik, Abt. Molekulargenetik, Universität Bonn, 53117 Bonn, Germany.
Jung
D
D
Bützler
C
C
Temme
A
A
Traub
O
O
Winterhager
E
E
Willecke
K
K
D019325:3-O-Methylglucose / Q000493:pharmacokinetics*; D000483:Alleles; D000818:Animals; D002250:Carbon Radioisotopes; D000072259:Connexin 26; D017630:Connexins / Q000172:deficiency / Q000235:genetics*; D004847:Epithelial Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D005260:Female; D017629:Gap Junctions / Q000737:chemistry; D006579:Heterozygote; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008817:Mice, Mutant Strains; D016296:Mutagenesis / Q000502:physiology; D010920:Placenta / Q000166:cytology / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000737:chemistry / Q000166:cytology; D013234:Stem Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D015017:Yolk Sac / Q000737:chemistry / Q000166:cytology
D002250:Carbon Radioisotopes; D017630:Connexins; D012333:RNA, Messenger; D000072259:Connexin 26; D019325:3-O-Methylglucose