The role of the visceral yolk sac in hyperglycemia‐induced embryopathies in mouse embryos in vitro

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Abstract
The adverse developmental effects of hyperglycemia to rodent embryos have been shown using whole embryo culture. Although, a mechanism by which hyperglycemia‐induced effects occur is unknown, recent work has focused on the visceral yolk sac as a potential target tissue. Therefore, we have evaluated the developmental effects of hyperglycemia in early head fold stage mouse embryos in vitro and assessed the histiotrophic function of the visceral yolk sac. As has been previously shown in rodents, hyperglycemia produced neural tube closure defects in a concentration dependent manner at 33, 50, and 67 mM glucose using a 44 h exposure period. However, exposure times between 6 and 12 h were sufficient to alter embryonic development when the glucose concentration was 50 or 67 mM. In contrast, early somite stage embryos (4‐6 somite stage) appear to be less sensitive to dysmorphogenesis and a 48 h exposure to 67 mM glucose but not 33 or 50 mM also produced neural tube defects. Hyperglycemia (67 mM) did not alter the uptake of 35S‐methionine and 35S‐cysteine‐labeled hemoglobin (35S‐Hb) in the visceral yolk sac (VYS) in early headfold staged embryos. However, the accumulation of 35S in the embryo was reduced by 16‐18% at glucose concentrations of 50 or 67 mM during the last 12 h of a 44 h exposure period. No effect on VYS uptake or embryonic accumulation of 35S‐labeled products was observed at shorter exposure periods (12‐24 and 24‐36 h). In early somite stage embryos hyperglycemia (⩾ 33 mM) reduced both VYS uptake and embryonic accumulation of 35S‐Hb during the last 12 h of a 48 h exposure period. However, there was no concentration dependent effect on the embryonic accumulation of 35S at the early somite stage. The time course for hyperglycemia‐induced effects on morphology and VYS histiotrophic function are different in the early head fold versus early somite staged embryos. Thus, at the early head fold stage malformations were induced only after a 6‐12 h exposure, while the histiotrophic function was reduced only during the 32‐44 h of exposure. Therefore, our study indicates that hyperglycemia can alter the histiotrophic function of the VYS following long exposure periods. The time course for alterations in VYS histiotrophic function is not correlated with that for induction of malformations but may be related to the growth reduction produced by long‐term exposure to hyperglycemia in vitro.

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