Abir R, Ornoy A
Laboratory of Teratology, Department of Anatomy and Embryology, Hebrew University-Hadassah Medical School, Jerusalem, Israel.
Am J Reprod Immunol. 1996 Feb;35(2):93-101. doi: 10.1111/j.1600-0897.1996.tb00013.x.
Spontaneous abortions due to immunological rejection of the embryo may be avoided by immunotherapy with paternal allogeneic leukocytes but there is no appropriate method to detect and differentiate this group of aborters from other groups.
In previous studies we have demonstrated that in about two-thirds of sera from women with spontaneous abortions the IgG antibodies are responsible (alone or in combination with other factors) for the embryotoxic effects of these sera on cultured rat embryos. We presently cultured 10.5-day-old rat embryos on highly teratogenic serum ("high risk" serum that induced anomalies in more than 50% of the embryos) from women with spontaneous abortions, where the IgG fraction was exchanged with IgG from control sera and vice-versa. We studied by Transmission Electron Microscopy (TEM) the extent of yolk sac damage in comparison to the rate of embryonic anomalies.
In cases where IgG antibodies were teratogenic, embryos cultured in control sera with IgG from "high risk" sera exhibited ultrastructural yolk sac damage as well as embryonic anomalies, and the yolk sacs cultured in "high risk" sera with control IgG were normal. In cases in which the IgG exchange did not change the rate of anomalies, as IgG was not teratogenic, yolk sacs from embryos cultured in "high risk" sera remained damaged, while yolk sacs from embryos cultured in control sera after IgG exchange stayed normal. Although no significant difference in total IgG levels was found between the groups, a higher IgG1 level in sera from women with teratogenic IgG was observed in comparison to control women's sera. The obstetrical history of the women with two or more abortions who took part in our study showed that there were more cases of unknown etiology of the abortion in the women from the "high risk" group.
The serum and the IgG fraction from women with habitual abortions can be tested in whole embryo culture to evaluate the embryonic and yolk sac damage. On this basis it may be possible to detect the women in whom the habitual abortions result from immunological rejection.
胚胎免疫排斥导致的自然流产可通过用父本同种异体白细胞进行免疫治疗来避免,但尚无合适的方法来检测并区分这组流产者与其他组。
在之前的研究中我们已证明,约三分之二自然流产女性的血清中,IgG抗体(单独或与其他因素共同作用)导致了这些血清对培养的大鼠胚胎产生胚胎毒性作用。我们目前在来自自然流产女性的高致畸性血清(“高风险”血清,能在超过50%的胚胎中诱发异常)上培养10.5日龄的大鼠胚胎,其中将IgG部分与对照血清的IgG进行交换,反之亦然。我们通过透射电子显微镜(TEM)研究了卵黄囊损伤程度与胚胎异常率的关系。
在IgG抗体具有致畸性的情况下,在含有来自“高风险”血清IgG的对照血清中培养的胚胎表现出超微结构的卵黄囊损伤以及胚胎异常,而在含有对照IgG的“高风险”血清中培养的卵黄囊是正常的。在IgG交换未改变异常率的情况下,由于IgG不具有致畸性,在“高风险”血清中培养的胚胎的卵黄囊仍有损伤,而IgG交换后在对照血清中培养的胚胎的卵黄囊保持正常。尽管各组之间总IgG水平未发现显著差异,但与对照女性血清相比,致畸性IgG女性血清中的IgG1水平更高。参与我们研究的有两次或更多次流产经历的女性的产科病史显示,“高风险”组女性中流产病因不明的病例更多。
习惯性流产女性的血清和IgG部分可在全胚胎培养中进行检测,以评估胚胎和卵黄囊损伤。在此基础上,有可能检测出习惯性流产是由免疫排斥引起的女性。