HLA sharing and fertility in Hutterite couples: evidence for prenatal selection against compatible fetuses.
HLA sharing and fertility in Hutterite couples: evidence for prenatal selection against compatible fetuses.
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哈特派夫妇的 HLA 共享和生育能力：针对相容胎儿的产前选择的证据。
DOI：
10.1111/j.1600-0897.1988.tb00245.x
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Bombard,A
中科院分区：
文献类型：
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作者：
Ober,C;Elias,S;O'Brien,E;Kostyu,DD;Hauck,WW;Bombard,A
母亲和胎儿之间的抗原差异(即血型不相容)传统上被认为对胎生繁殖有害。最近，越来越多的证据表明，母亲对父系来源的胎儿抗原的反应可能有助于维持妊娠。因此，其父系抗原与母体抗原没有区别的胎儿(即组织相容妊娠)在怀孕期间可能处于选择性劣势。共享组织相容性抗原(即，人类白细胞抗原)的父母可能会产生相容的胎儿，并表现出总体生育力下降。事实上，据报道，在一些反复自然流产的夫妇中，人类白细胞抗原共享增加。然而，人类白细胞抗原共享在因既往妊娠丢失而未被选中的夫妇中的影响尚未得到评估。为了阐明母胎组织相容性对生殖的影响，我们启动了基于人群的前瞻性研究，研究父母的人类白细胞抗原共享和哈特尔特人的生殖结局，哈特利特人是一个共同生活并禁止避孕的种群。对111对Hutterite夫妇进行了人类白细胞抗原-A、-B和-DR基因共享与生殖结局的关系研究。从结婚到每次出生的间隔时间不再存在于共享抗原的夫妇之间；第二次出生时差异显著，直到第六次出生时仍显著(P<；0.05)。当检验个体基因座共享的影响时，人类白细胞抗原-DR是唯一对出生间隔长度有显著预测作用的个体基因座(P=0.025)。共享和不共享HLA-DR的夫妇的完整家庭规模分别为6.5和9.0(P=0.082，双尾)。然而，在共享和不共享抗原的夫妇中，可识别的胎儿损失率没有差异。我们将这些结果解释为一些共享HLA的哈特族夫妇生育力下降的证据，这是由于母婴对HLA-DR本身的兼容性，或者是一个未定义的、与HLA-DR相关的基因座上的等位基因。我们的数据进一步表明，与HLA-DR共享相关的较长时间间隔可能是由于在Hutterites人认识到怀孕之前妊娠早期发生的损失造成的。
Antigenic differences between mother and fetus (i.e., blood group incompatibilities) were traditionally considered deleterious for viviparous reproduction. Recently, evidence has accumulated suggesting that maternal response to paternally derived fetal antigens, paradoxically, may facilitate maintenance of pregnancy. Thus, fetuses whose paternally derived antigens do not differ from maternal antigens (i.e., histocompatible pregnancies) may be at a selective disadvantage during pregnancy. Parents sharing histocompatibility antigens (i.e., HLA) may produce compatible fetuses and show overall reduced fertility. Indeed, increased HLA sharing has been reported in some couples experiencing repetitive spontaneous abortion. However, the effects of HLA sharing in couples not selected because of previous pregnancy losses have not been assessed. To elucidate the reproductive effects of maternal‐fetal histocompatibility, we initiated prospective population‐based studies of parental HLA sharing and reproductive outcome in the Hutterites, a population isolate that lives communally and proscribes contraception. The relationship between HLA‐A, ‐B, and ‐DR sharing and reproductive outcome was examined in 111 Hutterite couples. Intervals from marriage to each birth were no longer among couples sharing antigens; differences were significant at the second birth and remained significant through the sixth birth (P < .05). When the effects of sharing at individual loci were examined, HLA‐DR was the only individual locus that was a significant predictor of birth interval length (P = .025). Completed family sizes were 6.5 and 9.0 among couples sharing and not sharing HLA‐DR, respectively (P = .082, 2‐tailed). However, recognized fetal loss rates did not differ among couples sharing and not sharing antigens.We interpret these results as evidence for reduced fertility among some Hutterite couples sharing HLA, as a result of maternal‐fetal compatibility for HLA‐DR, per se, or alleles at an undefined, HLA‐DR‐linked locus. Our data further suggest that longer intervals associated with HLA‐DR sharing may result from losses occurring early in gestation, before Hutterites would recognize pregnancy.