Ober C
Department of Obstetrics and Gynecology, MC2050, University of Chicago, Illinois 60637, USA.
Placenta. 1995 Oct;16(7):569-77. doi: 10.1016/0143-4004(95)90026-8.
The paradoxical observation that maternal-fetal incompatibility with respect to human leucocyte antigen (HLA) genes was not associated with spontaneous abortion, stillbirths or developmental abnormalities led to the hypothesis that fetuses with paternally-derived HLA that differ from maternal HLA may enjoy a selective advantage during pregnancy. If true, then couples who share HLA should experience poorer reproductive outcome than couples not sharing HLA. Numerous, retrospective studies of parental HLA sharing and fetal wastage in humans have yielded conflicting results and discrepancies are difficult to reconcile because of methodological differences among studies and potential heterogeneity among subjects. To explore the hypothesis that maternal-fetal HLA compatibility is deleterious in human pregnancy, we initiated prospective and population-based studies in the Hutterites, a religious isolate that lives communally and proscribes contraception. Our data suggest that HLA-DR-linked genes may affect fertilization or implantation and HLA-B-linked genes may contribute toward recognized fetal loss. Discrepant results among retrospective studies of outbred couples may be due to the fact that more than one HLA region influences reproductive outcome and that the genes influencing fertility may not be HLA genes per se, but loci in linkage disequilibrium with HLA-B and HLA-DR.
关于人类白细胞抗原（HLA）基因，母胎不相容性与自然流产、死产或发育异常并无关联，这一矛盾的观察结果引发了一种假说，即父源HLA与母源HLA不同的胎儿在孕期可能具有选择性优势。如果这一假说成立，那么拥有相同HLA的夫妇相较于不具有相同HLA的夫妇，生殖结局应该更差。众多针对人类父母HLA共享与胎儿丢失情况的回顾性研究结果相互矛盾，由于各研究在方法上存在差异且研究对象可能具有潜在异质性，这些差异难以协调。为了探究母胎HLA相容性在人类孕期具有有害影响这一假说，我们在哈特派开展了前瞻性的基于人群的研究，哈特派是一个群居且禁止避孕的宗教群体。我们的数据表明，与HLA-DR相关的基因可能会影响受精或着床，而与HLA-B相关的基因可能会导致已确认的胎儿丢失。对于非近亲通婚夫妇的回顾性研究结果存在差异，可能是因为不止一个HLA区域会影响生殖结局，而且影响生育能力的基因本身可能并非HLA基因，而是与HLA-B和HLA-DR处于连锁不平衡状态的基因座。
