American journal of reproductive immunology and microbiology : AJRIM最新文献

When all known causes of fetal losses are ruled out, there remains a small population of women (0.5-1.0%) who have recurrent fetal losses of unknown etiology. A significant proportion of these recurrent spontaneous abortions may be due to primarily genetic causes. The critical characteristic of couples experiencing such fetal losses is the sharing of HLA antigens between husband and wife. The hypothesis developed here states that the sharing of HLA antigens indicates the sharing of recessive lethal genes linked to the major histocompatibility antigens (MHC) and that the sharing of the antigens per se is not significant. These recessive lethal genes could act alone to cause fetal death, or they could act epistatically with lethal genes on other chromosomes. Several models of such genetic mechanisms and the observations from studies in experimental animals and from studies in humans to support these models are presented.

Approximately 80% of all human conceptions are lost prior to term, and about 6% of all human newborns exhibit in-utero fetal growth retardation resulting in perinatal mortality and a major share of perinatal morbidity. Recent interest has focused on the plausibility of an MHC-linked immunological effect in cases of spontaneous abortions in which no possible cause, particularly a chromosome abnormality, is indicated. Paradoxically, placenta has been shown to serve as an efficient immunosorbent where antipaternal MHC antibodies on binding to target MHC antigen-bearing placenta are internalized and rapidly degraded, thereby preventing potential damage to the fetus. We, in our attempts to resolve if active immune responses on the part of female following early recognitive events during pregnancy play any decisive role in the reproductive process, raised a highly inbred colony of mice (Balb/cJ, Jackson Labs, USA) to produce H-Y antibodies. An outbred colony of mice (Swiss, AIIMS) was maintained to study the cumulated effect of H-Y and H-2 antibodies on the sex ratio, reproductive performance, litter size, and fetal wastage. A definite sex ratio was observed in control groups. However, the H-Y antibodies produced by hyperimmunized inbred female mice before fertilization, significantly (P less than 0.01) reduced the sex ratio. The combined effect of H-Y and H-2 antibodies on the pregnant outbred mice produced more lethal congenital abnormalities. There was a significant (P less than or equal to 0.01) loss in the reproductive performance of male mice born from hyperimmunized female mice both inbred and outbred colonies.(ABSTRACT TRUNCATED AT 250 WORDS)

Both retrospective studies of idiopathic aborters, as well as prospective studies of normal couples, have shown reduced fertility among couples sharing HLA antigens. However, the effects of maternal-fetal histocompatibility on surviving embryos are largely univestigated. We thus prospectively studied 53 healthy, fertile women whose timed pregnancies were verified within 21 days of conception. Maternal-fetal histocompatibility status was determined for HLA-A,-B, and -DR locus antigens. Fetal growth rates were monitored by ultrasound at 8, 12, and 20 weeks gestation. Neonates were weighed, measured (birthlength, chest circumference, head circumference), and examined within 72 h of delivery (116 major and minor anomalies) in standardized fashion by one of two geneticists. Although no significant differences were found between infants compatible and incompatible at the HLA-A or HLA-B locus, significant differences were observed between HLA-DR compatible and incompatible infants for sex ratios (p less than .003) and minor anomaly rates (p less than .05). Although differences in mean birthweights between HLA-DR compatible and incompatible infants were not significant in this sample, HLA-DR compatible infants were on average 200 grams smaller than HLA-DR incompatible infants. We interpret these findings as evidence for selection against histocompatible fetuses throughout gestation, particularly with respect to HLA-DR compatibility. Potential immunologic and genetic mechanisms are discussed.

Although implicated in the etiology of unexplained infertility, a primary role for antibodies to zona pellucida antigens remains uncertain. We therefore prospectively studied 21 infertility patients found to have significant anti-zona pellucida antibody titers (1:4 to 1:16). When treated for endometriosis or other concurrent fertility problems, 7 of the 21 (33%) delivered viable infants. Two other patients conceived without treatment. Decreases in anti-zona antibody titers were found in most but not all women with successful outcomes. In a given individual, anti-zona antibodies may coexist with other fertility disorders. Therefore, these antibodies should not preclude treatment of concurrent fertility disorders.