THE ROLE OF THE VISCERAL YOLK-SAC IN HYPERGLYCEMIA-INDUCED EMBRYOPATHIES IN MOUSE EMBRYOS INVITRO
THE ROLE OF THE VISCERAL YOLK-SAC IN HYPERGLYCEMIA-INDUCED EMBRYOPATHIES IN MOUSE EMBRYOS INVITRO
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DOI：
10.1002/tera.1420450213
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发表时间：
1992-02-01
期刊：
影响因子：
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通讯作者：
SADLER, TW
中科院分区：
文献类型：
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作者：
HUNTER, ES;SADLER, TW
高血糖对啮齿类动物胚胎的不良发育影响已通过全胚胎培养显示出来。虽然，高血糖诱导的作用发生的机制是未知的，最近的工作集中在内脏卵黄囊作为一个潜在的靶组织。因此，我们评估了高血糖对体外培养的早期头褶期小鼠胚胎发育的影响，并评估了内脏卵黄囊的组织营养功能。如先前在啮齿动物中所示，在33、50和67 mM葡萄糖下使用44 h暴露期，高血糖以浓度依赖性方式产生神经管闭合缺陷。然而，6和12小时之间的曝光时间足以改变胚胎发育时，葡萄糖浓度为50或67毫米。相比之下，早期体节阶段胚胎（4-6体节阶段）似乎是不太敏感的畸形和48小时暴露于67毫米的葡萄糖，但不是33或50毫米也产生神经管缺陷。高胆红素（67 mM）没有改变早期头折叠阶段胚胎内脏卵黄囊（VYS）中S-35-蛋氨酸和S-35-半胱氨酸标记血红蛋白（S-35-Hb）的摄取。然而，在44小时暴露期的最后12小时期间，在50或67 mM的葡萄糖浓度下，胚胎中S-35的积累减少了16-18%。在较短的暴露时间（12-24和24-36 h）内，未观察到对VYS摄取或S-35标记产物的胚胎蓄积的影响。在早期体节阶段胚胎高血糖症（大于或等于33毫米）减少VYS吸收和胚胎积累的S-35-Hb在最后12小时的48小时曝光期间。然而，没有浓度依赖性效应的胚胎积累的S-35在早期体节阶段。高血糖诱导的形态学和VYS组织营养功能的影响的时间过程是不同的，在早期头折叠与早期体节阶段的胚胎。因此，在早期的头部褶皱阶段畸形诱导后6-12小时的曝光，而histiotrophic功能降低，只有在32-44小时的曝光。因此，我们的研究表明，高血糖症可以改变VYS的组织营养功能后，长时间暴露。VYS组织营养功能改变的时间过程与诱导畸形不相关，但可能与体外长期暴露于高血糖所产生的生长减少有关。
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 S-35-methionine and S-35-cysteine-labeled hemoglobin (S-35-Hb) in the visceral yolk sac (VYS) in early headfold staged embryos. However, the accumulation of S-35 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 S-35-labeled products was observed at shorter exposure periods (12-24 and 24-36 h). In early somite stage embryos hyperglycemia (greater-than-or-equal-to 33 mM) reduced both VYS uptake and embryonic accumulation of S-35-Hb during the last 12 h of a 48 h exposure period. However, there was no concentration dependent effect on the embryonic accumulation of S-35 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.