Reproduction Abstracts

Introduction: During pregnancy, the maternal immune system has to tolerate the semi-allogenic fetus while protecting the mother and the unborn against pathogens. Subclinical infections that danger the fetus constitute a challenge for the medical system. A useful model to study mechanisms underlying infection-driven fetal death is a LPS-based mouse model. The recognition of LPS, a component of gram-negative bacteria membrane, leads to an immune answer that takes place through TLR4 signaling. In this pathway, MyD88 plays an important role. Having recently shown that IL-10 secreting B cells are important components of the maternal immune response, we now aim to investigate the participation of MyD88 in B cell-mediated fetal protection.

Methods: B cell specific MyD88 knockout mice were generated by mating CD19^cre.in and MyD88^flox/flox animals. Following female animals were included in our study: wildtype (WT), CD19^cre/wt/MyD88^flox/flox with MyD88 deficiency in B cells (Het/KO) and CD19^cre/cre/MyD88^flox/flox lacking B cells and MyD88 (KO/KO). After successful pairing with BALB/c males, LPS (0.6 μl/animal) or PBS was injected at day 10 of the pregnancy. 24 hours later the animals are sacrificed, fetal death rate was determined and tissues were harvested for histological examinations.

Results and Discussion: Animals with B cell specific MyD88 deficiency had an increased fetal death rate compared to all other groups. It seems that the absence of MyD88 in B cells leads to the lethal effect of LPS, while total B cell absence leads only to a mild impact of LPS on fetal survival. Furthermore these animals had thicker spiral arteries compared to the PBS-Group. Ongoing studies will help understanding whether the absence of MyD88 in B cells hinders the secretion of IL-10 and by doing so, dangers fetal survival. Our data sheds light upon novel mechanisms of fetal protection that are worth to be further studied.