Neuer A, Spandorfer S D, Giraldo P, Jeremias J, Dieterle S, Korneeva I, Liu H C, Rosenwaks Z, Witkin S S
Department of Obstetrics and Gynecology, University of Witten/Herdecke, Dortmund, Germany.
Infect Dis Obstet Gynecol. 1999;7(1-2):10-6. doi: 10.1155/S1064744999000034.
When cells are subjected to various stress factors, they increase the production of a group of proteins called heat shock proteins (hsp). Heat shock proteins are highly conserved proteins present in organisms ranging from bacteria to man. Heat shock proteins enable cells to survive adverse environmental conditions by preventing protein denaturation. Thus the physiological and pathological potential of hsps is enormous and has been studied widely over the past two decades. The presence or absence of hsps influences almost every aspect of reproduction. They are among the first proteins produced during mammalian embryo development. In this report, the production of hsps in gametogenesis and early embryo development is described. It has been suggested that prolonged and asymptomatic infections trigger immunity to microbial hsp epitopes that are also expressed in man. This may be relevant for human reproduction, since many couples with fertility problems have had a previous genital tract infection. Antibodies to bacterial and human hsps are present at high titers in sera of many patients undergoing in vitro fertilization. In a mouse embryo culture model, these antibodies impaired the mouse embryo development at unique developmental stages. The gross morphology of these embryos resembled cells undergoing apoptosis. The TUNEL (terminal deoxynucleotidyl transferase-mediated X-dUTP nick end labeling) staining pattern, which is a common marker of apoptosis, revealed that embryos cultured in the presence of hsp antibodies stained TUNEL-positive more often than unexposed embryos. These data extend preexisting findings showing the detrimental effect of immune sensitization to hsps on embryo development.
当细胞受到各种应激因素影响时,它们会增加一组称为热休克蛋白(hsp)的蛋白质的产生。热休克蛋白是高度保守的蛋白质,存在于从细菌到人类的各种生物体中。热休克蛋白通过防止蛋白质变性使细胞能够在不利的环境条件下存活。因此,热休克蛋白的生理和病理潜力巨大,在过去二十年中得到了广泛研究。热休克蛋白的存在与否几乎影响生殖的方方面面。它们是哺乳动物胚胎发育过程中最早产生的蛋白质之一。在本报告中,描述了热休克蛋白在配子发生和早期胚胎发育中的产生情况。有人提出,长期无症状感染会引发对微生物热休克蛋白表位的免疫反应,而这些表位在人类中也有表达。这可能与人类生殖有关,因为许多有生育问题的夫妇以前曾有过生殖道感染。在许多接受体外受精的患者血清中,针对细菌和人类热休克蛋白的抗体呈高滴度存在。在小鼠胚胎培养模型中,这些抗体在独特的发育阶段损害了小鼠胚胎的发育。这些胚胎的总体形态类似于正在经历凋亡的细胞。TUNEL(末端脱氧核苷酸转移酶介导的dUTP缺口末端标记)染色模式是凋亡的常见标志物,它显示在热休克蛋白抗体存在下培养的胚胎比未接触抗体的胚胎更常出现TUNEL阳性染色。这些数据扩展了先前的研究结果,表明对热休克蛋白的免疫致敏对胚胎发育有有害影响。