Brent R L, Beckman D A, Jensen M, Koszalka T R
Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Teratology. 1990 Apr;41(4):405-13. doi: 10.1002/tera.1420410406.
Our investigations concerning the importance of cell surface macromolecules during embryonic development led us to the discovery in 1961 that heterologous anti-rat kidney serum produced teratogenesis, growth retardation and embryonic death when injected into the pregnant rat during early organogenesis. It was established that IgG was the teratogenic agent, primarily directed against the visceral yolk sac (VYS) but not the embryo. Heterologous anti-rat VYS serum was prepared which was teratogenic localized in the VYS and served as a model for producing VYS dysfunction and embryonic malnutrition. The role of the yolk sac placenta in histiotrophic nutrition is now recognized to be critical for normal embryonic development during early organogenesis in the rodent. VYS antiserum affects embryonic development primarily by inhibiting endocytosis of proteins by the VYS endoderm, resulting in a reduction in the amino acids supplied to the embryo. Our laboratory has recently developed teratogenic monoclonal yolk sac antibodies (MCA) which can be utilized; to study VYS plasma membrane synthesis and recycling, to compare yolk sac function among different species, and to identify components of the plasma membrane involved in pinocytosis. MCA prepared against certain VYS antigens provide an opportunity to study embryonic nutrition with minimal interference with the nutritional state of the mother. Recent developments in the study of the human yolk sac along with our laboratory's ability to isolate a spectrum of yolk sac antigens, prepare monoclonal antibodies, and perform functional studies, should provide information that will increase our understanding of yolk sac function and dysfunction in the human and determine the relative importance of various amino acids to normal development during mammalian organogenesis.
我们对胚胎发育过程中细胞表面大分子重要性的研究，使我们在1961年发现，在器官形成早期将异种抗大鼠肾血清注射到怀孕大鼠体内时，会导致致畸、生长迟缓及胚胎死亡。已确定IgG是致畸剂，主要针对内脏卵黄囊（VYS）而非胚胎。制备了异种抗大鼠VYS血清，其致畸作用局限于VYS，可作为产生VYS功能障碍和胚胎营养不良的模型。现在人们认识到，卵黄囊胎盘在组织营养性营养中的作用对于啮齿动物器官形成早期的正常胚胎发育至关重要。VYS抗血清主要通过抑制VYS内胚层对蛋白质的内吞作用来影响胚胎发育，从而导致供应给胚胎的氨基酸减少。我们实验室最近开发了可用于研究VYS质膜合成与循环利用、比较不同物种间卵黄囊功能以及鉴定参与胞饮作用的质膜成分的致畸性单克隆卵黄囊抗体（MCA）。针对某些VYS抗原制备的MCA为研究胚胎营养提供了一个机会，且对母体营养状态的干扰最小。人类卵黄囊研究的最新进展，以及我们实验室分离一系列卵黄囊抗原、制备单克隆抗体并进行功能研究的能力，应能提供相关信息，增进我们对人类卵黄囊功能及功能障碍的理解，并确定各种氨基酸在哺乳动物器官形成过程中对正常发育的相对重要性。
