leukotriene-b4 and Fetal-Resorption

Female CBA/J mice mated with DBA/2 males exhibit an increased spontaneous resorption rate (30-35%) in their first pregnancy. Second pregnancies show a decreased resorption rate (15-20%). In contrast, resorption in CBA/J females mated with BALB/c males (identical to DBA/2 at the H-2 major histocompatibility locus) occurs with a frequency of 5-10%. Resorption is preceded by fetoplacental infiltration of natural killer (NK)-like cells and a deficiency in a lipophilic NK-suppressive activity. The eicosanoids leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are known to modulate NK activity in vitro. We measured the concentrations of LTB4 and PGE2 in extracts of individual fetoplacental units at Day 8 of gestation from (1) primigravid CBA/J x DBA/2 resorption-prone matings (RES); (2) second CBA/J x DBA/2 matings (SEC); and (3) primigravid CBA/J x BALB/c control matings (CON). We detected a significant decrease in the mean concentration of LTB4 in RES fetoplacental units (176.4 +/- 11.8 pg/ml; n = 42) compared with CON and SEC fetoplacental units (570.2 +/- 45.5 pg/ml; n = 21 and 420.2 +/- 59.5 pg/ml; n = 39, respectively). To confirm that the LTB4 deficiency is associated with decreased NK suppression in RES matings, we supplemented RES extracts, in vitro, with exogenous LTB4 (0-500 pg/ml). The effect of the addition of LTB4 to RES extracts was biphasic. Addition of LTB4 in the range of 30-125 pg/ml increased the extract's NK suppressive capacity, whereas LTB4 alone either stimulated NK activity or was without effect. These results suggest a critical role for LTB4 in averting NK-mediated early spontaneous fetal resorption.

Topics: Animals; Dinoprostone; Female; Fetal Resorption; Killer Cells, Natural; Leukotriene B4; Male; Mice; Mice, Inbred BALB C; Mice, Inbred CBA; Mice, Inbred DBA; Pregnancy; Pregnancy Outcome; Pregnancy, Animal; Prevalence