Compensatory fetal membrane mechanisms between biglycan and decorin in inflammation

Preterm premature rupture of fetal membranes (PPROM) is associated with infection and is one of the most common causes of preterm birth. Abnormalities of biglycan and decorin, two extracellular matrix proteoglycans, lead to preterm birth and abnormal fetal membrane morphology and abnormal signaling in the mouse model as well as being associated with inflammatory cascades. In humans, decorin dysregulation is associated with inflammation in PPROM. We investigated biglycan and decorin’s role in inflammation in fetal membranes using mouse models of intraperitoneal E. coli injections superimposed on biglycan and decorin deficiency. We assessed outcomes in vivo as well as in vitro using quantitative qPCR, Western blotting and ELISA techniques. Our results suggest that biglycan and decorin compensate for each other in the fetal membranes but lose the ability to do so in the setting of inflammation, leading to decreased latency to preterm birth. Furthermore, our findings suggest that biglycan and decorin play discrete roles in fetal membrane signaling pathways in inflammation, leading to changes in expression of MMP-8 and collagen α1VI, two components of the fetal membrane extracellular matrix that play a role in the pathophysiology of PPROM. In summary, these findings underline the importance of biglycan and decorin in fetal membranes as targets for the manipulation of fetal membrane extracellular matrix stability in the setting of inflammation.