Oral 1 - 1.4
1,5Antara Chatterjee, 2Kartik Jhaveri, 4John Sled, 3Wendy Whittle, 1,3,5Stephen Lye, 1,3,5Oksana Shynlova
1 Department of Physiology, University of Toronto; 2 Department of Medical Imaging, Princess Margaret Hospital; 3 Department of Obstetrics and Gynecology, University of Toronto; 4 Department of Medical Biophysics, University of Toronto; 5 Lunenfeld-Tanenbaum Research Institute at Sinai Health System
INTRODUCTION: Preterm birth (PTB) rates are increasing worldwide while current methods of its prediction and prevention are inadequate. We hypothesize that a sensitive screening tool for PTB can be developed by combining biochemical analyses of the extracellular matrix (ECM) and magnetic resonance imaging (MRI) of the cervix during pregnancy, and that cervical changes observed during term labor (TL) will be similar during preterm labor (PTL) thus improving PTB prediction. METHODS: Cervical tissues were collected from non-pregnant and pregnant CD-1 mice at gestational day (GD) 15, 17, 18, 19.5 and during TL (n=4/GD). To mimic idiopathic or infection-induced PTL, mice were injected with progesterone receptor antagonist RU486 or lipopolysaccharide (LPS) on GD15 (n=4/group) and sacrificed during PTL. RT-qPCR was used to evaluate gene expression of structural proteins (Col1 and Col3), proteins involved in ECM synthesis (Has2) and maturation (Bmp1, Adamts14, and Lox). One-way ANOVA was used for statistical analyses. Using a 7-tesla scanner, a T2-weighted and a diffusion tensor imaging MRI sequence was applied to assess structural changes in the mouse cervix across gestation. RESULTS: mRNA levels of major ECM proteins (Col1, Col3, Adamts14, Bmp1, and Lox) were significantly (p<0.05) downregulated in the mouse cervix during TL and LPS-induced PTL. Cervical Has2 was significantly (p<0.05) upregulated during TL, but was not induced in the PTB models. MRI studies on mice showed decreased cervical length across term gestation and dramatic changes along the cervical canal, and a loss of structural integrity in the cervical stroma prior to term delivery. CONCLUSION: Decreased rigidity of the murine cervix is caused by changes in the ECM composition in preparation for labor, providing a molecular basis for the structural changes seen in MRI. Similar cervical changes can be seen in the PTB models thus showing the potential of combining biochemical analyses and MRI as a novel screening tool for PTB prediction.