Brent R L, Fawcett L B
Department of Pediatrics, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania.
J Pediatr. 1998 Mar;132(3 Pt 2):S6-16. doi: 10.1016/s0022-3476(98)70522-0.
In 1961 we reported that heterologous kidney antiserum when injected into pregnant rats resulted in wide spectrum of congenital malformations. Further studies identified that it was the IgG component of the antiserum that was teratogenic and that complement was not necessary to produce the teratogenic effect. Labeled antibody studies demonstrated that the kidney antiserum localized in the kidney and in the visceral yolk sac (VYS) and parietal yolk sac placentas. Preparation of yolk sac (YS) antiserum proved to be more potent than the kidney antiserum. Adsorption studies with VYS and parietal yolk sac antiserum revealed that the site of the teratogenic process was located in the VYS. In vitro embryo culture experiments demonstrated that direct injection of the teratogenic antibody into the amniotic or YS cavity did not injure the embryo, thus indicating that the teratogenic antibody had to come in contact with the absorptive surface of the VYS. Collaboration with Dr. John Lloyd demonstrated that teratogenic antibody interfered with the process of pinocytosis and the delivery of amino acids (AA) to the developing embryo. Our studies into the nature of the source of AA for the embryo indicated that in some instances > 95% of the AA present in the developing embryo were derived from maternal proteins and the remainder from free AA in the maternal serum. We also demonstrated that embryonic methionine was derived primarily from the digestion of maternal serum proteins but that more of the methionine was diverted from the synthesis of embryonic proteins, supporting the view that it has important functions other than the synthesis of proteins. All these studies focus on the role of the YS in human development and whether human YS dysfunction may play a role in the pathogenesis of congenital malformations. Further studies on the delivery of AA to the embryo are warranted to determine whether certain AA are in short supply in maternal serum and place the embryo at risk if nutritional alterations in the maternal environment occurs. Furthermore, the YS may be an organ whose role might offer opportunities for pregnancy control.
1961年我们报道，将异种肾抗血清注射到怀孕大鼠体内会导致多种先天性畸形。进一步研究发现，抗血清中的IgG成分具有致畸性，且补体对于产生致畸作用并非必需。标记抗体研究表明，肾抗血清定位于肾脏以及内脏卵黄囊（VYS）和壁层卵黄囊胎盘。卵黄囊（YS）抗血清的制备被证明比肾抗血清更有效。用VYS和壁层卵黄囊抗血清进行的吸附研究表明，致畸过程的部位位于VYS。体外胚胎培养实验表明，将致畸抗体直接注射到羊膜腔或YS腔不会损伤胚胎，因此表明致畸抗体必须与VYS的吸收表面接触。与约翰·劳埃德博士合作表明，致畸抗体干扰了胞饮作用以及氨基酸（AA）向发育中胚胎的传递。我们对胚胎AA来源性质的研究表明，在某些情况下，发育中胚胎中存在的AA > 95%源自母体蛋白质，其余来自母体血清中的游离AA。我们还证明，胚胎蛋氨酸主要源自母体血清蛋白的消化，但更多的蛋氨酸从胚胎蛋白合成中转移出来，支持了其除蛋白质合成外还有重要功能的观点。所有这些研究都聚焦于YS在人类发育中的作用以及人类YS功能障碍是否可能在先天性畸形的发病机制中起作用。有必要对AA向胚胎的传递进行进一步研究，以确定母体血清中某些AA是否供应不足，以及如果母体环境发生营养改变是否会使胚胎处于风险中。此外，YS可能是一个其作用可能为控制妊娠提供机会的器官。
