Maternal Endotoxin-induced Fetal Growth Restriction in Rats: Fetal Responses in Toll-like Receptor

Abstract

Background: Porphyromonas gingivalis as a major etiology of periodontal disease can produce virulence factor, lipopolysaccharide/LPS, which is expected to play a role in the intrauterine fetal growth. Trophoblast at the maternal-fetal interface actively participates in response to infection through the expression of a family of natural immune receptors, Toll-like receptor (TLR). Purpose: This study was aimed to identify endotoxin concentration in maternal blood serum of Porphyromonas gingivalis-infected pregnant rats, to characterize the TLR-4 expression in trophoblast cells, and to determine its effect on fetal growth. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2 x 109 colony forming unit/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrified on gestational day 14 and 20. Fetuses were evaluated for weight and length. Endotoxin was detected by limulus amebocyte lysate assay in the maternal blood serum. The TLR-4 expression in trophoblast cells was detected by immunohistochemistry. Results: The mean of LPS concentrations in maternal blood serum was significantly different (p<0.05) among the four maternal periodontal infection groups. The TLR-4 expressions in syncytiotrophoblast, spongitrophoblast and trophoblastic giant cells from Porphyromonas gingivalis- infected periodontal maternal groups were significantly higher than the control group (p<0.05). Maternal endotoxemia affected (p<0.05) the fetal weight and fetal length. Conclusion: The increased LPS concentration in maternal blood serum resulted in the decreased fetal weight and fetal length. Syncytiotrophoblast, spongitrophoblast and trophoblastic giant cell were able to recognize Porphyromonas gingivalis LPS through the TLR-4 expression. This findings strengthened the link between periodontal disease and fetal growth restriction.