Balkan W, Phillips L S, Goldstein S, Sadler T W
Department of Cell Biology and Anatomy, University of North Carolina, Chapel Hill 27599-7090.
J Exp Zool. 1989 Jan;249(1):36-40. doi: 10.1002/jez.1402490108.
A low molecular weight somatomedin inhibitory serum fraction (SI), obtained from streptozotocin-induced diabetic rats, causes morphological abnormalities and growth reduction in mouse embryos grown in whole embryo culture (WEC). These abnormalities are thought to be caused, at least in part, by a failure of the visceral yolk sac (VYS) to properly degrade proteins, a process that normally provides the conceptus with amino acids and peptides for de novo protein synthesis (histiotrophic nutrition). To test this hypothesis, embryos exposed to the SI were provided with a mixture of ten essential amino acids (supplemented group) in an attempt to circumvent SI-induced VYS dysfunction. Results showed that 82.4% (14/17) of embryos in the amino acid-supplemented group exhibited improved growth and development compared to those embryos exposed to medium containing the SI alone (unsupplemented group). Supplemented embryos showed greater expansion of the brain regions, improved visceral arch development, and increased protein content compared to nonsupplemented SI-treated embryos. However, these parameters were still reduced compared to controls. VYSs from both the unsupplemented and amino acid-supplemented groups were identical with respect to alterations in morphology and increased protein content compared to VYSs from conceptuses cultured in control medium (with or without amino acid supplementation). The improvement in embryonic growth and development due to amino acid supplementation in spite of VYS abnormalities supports the hypothesis that nutritional deprivation is one aspect of SI-induced teratogenesis.
从链脲佐菌素诱导的糖尿病大鼠中获得的一种低分子量生长调节素抑制血清组分（SI），会导致在全胚胎培养（WEC）中生长的小鼠胚胎出现形态异常和生长减缓。这些异常被认为至少部分是由于内脏卵黄囊（VYS）无法正常降解蛋白质所致，而这一过程通常为胚胎提供氨基酸和肽用于从头合成蛋白质（组织营养）。为了验证这一假设，给暴露于SI的胚胎提供了十种必需氨基酸的混合物（补充组），试图规避SI诱导的VYS功能障碍。结果显示，与仅暴露于含SI培养基的胚胎（未补充组）相比，氨基酸补充组中82.4%（14/17）的胚胎生长和发育得到改善。与未补充SI处理的胚胎相比，补充氨基酸的胚胎脑区扩张更大，内脏弓发育改善，蛋白质含量增加。然而，与对照组相比，这些参数仍然降低。与在对照培养基（有或无氨基酸补充）中培养的胚胎的VYS相比，未补充组和氨基酸补充组的VYS在形态改变和蛋白质含量增加方面是相同的。尽管VYS存在异常，但氨基酸补充仍使胚胎生长和发育得到改善，这支持了营养剥夺是SI诱导致畸的一个方面这一假设。
