Rosa Viviane Souza, Castelucci Bianca Gazieri, Moreira Monica, Joazeiro Paulo Pinto, Consonni Sílvio Roberto
Department of Biochemistry and Tissue Biology, Institute of Biology (IB), State University of Campinas (Unicamp), Campinas 13083-970, Brazil.
MRC Laboratory of Molecular Biology, Francis Crick Avenue, Trumpington, Cambridge CB2 0QH, UK.
Int J Mol Sci. 2025 May 31;26(11):5307. doi: 10.3390/ijms26115307.
During mouse pregnancy, the pubic symphysis (PS) undergoes a gradual transitioning into an interpubic ligament (IpL) for a successful delivery. After birth, this IpL is rapidly remodeled, returning to the non-pregnant morphology. The PS fibrocartilaginous cells acquire a myofibroblast-like phenotype, characterized by extracellular matrix (ECM) secretion, expression of α-smooth muscle actin (α-SMA), and vimentin. While the presence of myofibroblast-like cells during the IpL remodeling is well described, cell-cell interactions and how this might contribute to the delivery remains poorly understood. This study uses ultrastructure and molecular approaches to investigate cell-cell and cell-ECM junctions during mouse pregnancy and postpartum. Our findings reveal that the intercellular contacts between adjacent IpL myofibroblast-like cells, particularly at late pregnancy stages, are characterized as adherens and GAP junctions. The acquisition of contractile elements by IpL cells, coupled with neighboring cells and the surrounding ECM via junctional complexes, suggests an important role in supporting changes in the mechanical forces generated by pubic bone movements during mouse pregnancy and also in tying the pelvic bones together, which may help the birth canal closure after delivery. Further studies in PS biology may investigate fibroblast to myofibroblast differentiation signaling cascades, which regulate the expression of pro-fibrotic proteins and may provide new insights for preterm labor.
在小鼠怀孕期间,耻骨联合(PS)会逐渐转变为耻骨间韧带(IpL)以实现顺利分娩。出生后,这种IpL会迅速重塑,恢复到非怀孕时的形态。PS纤维软骨细胞获得成肌纤维细胞样表型,其特征是细胞外基质(ECM)分泌、α平滑肌肌动蛋白(α-SMA)和波形蛋白的表达。虽然在IpL重塑过程中成肌纤维细胞样细胞的存在已有充分描述,但细胞间相互作用以及这可能如何促进分娩仍知之甚少。本研究采用超微结构和分子方法来研究小鼠怀孕和产后期间的细胞间及细胞与ECM的连接。我们的研究结果表明,相邻IpL成肌纤维细胞样细胞之间的细胞间接触,尤其是在怀孕后期,其特征为黏附连接和缝隙连接。IpL细胞通过连接复合体获得收缩元件,并与相邻细胞和周围的ECM相互作用,这表明其在支持小鼠怀孕期间耻骨运动产生的机械力变化以及将骨盆骨连接在一起方面发挥着重要作用,这可能有助于分娩后产道闭合。对PS生物学的进一步研究可能会探究成纤维细胞向成肌纤维细胞分化的信号级联反应,该反应调节促纤维化蛋白的表达,并可能为早产提供新的见解。