Department of Obstetrics and Gynecology, The Cecil H. and Ida Green Center for Reproductive Biology Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Biol Reprod. 2011 May;84(5):1053-62. doi: 10.1095/biolreprod.110.089599. Epub 2011 Jan 19.
A greater understanding of the parturition process is essential in the prevention of preterm birth, which occurs in 12.7% of infants born in the United States annually. Cervical remodeling is a critical component of this process. Beginning early in pregnancy, remodeling requires cumulative, progressive changes in the cervical extracellular matrix (ECM) that result in reorganization of collagen fibril structure with a gradual loss of tensile strength. In the current study, we undertook a detailed biochemical analysis of factors in the cervix that modulate collagen structure during early mouse pregnancy, including expression of proteins involved in processing of procollagen, assembly of collagen fibrils, cross-link formation, and deposition of collagen in the ECM. Changes in these factors correlated with changes in the types of collagen cross-links formed and packing of collagen fibrils as measured by electron microscopy. Early in pregnancy there is a decline in expression of two matricellular proteins, thrombospondin 2 and tenascin C, as well as a decline in expression of lysyl hydroxylase, which is involved in cross-link formation. These changes are accompanied by a decline in both HP and LP cross-links by gestation Days 12 and 14, respectively, as well as a progressive increase in collagen fibril diameter. In contrast, collagen abundance remains constant over the course of pregnancy. We conclude that early changes in tensile strength during cervical softening result in part from changes in the number and type of collagen cross-links and are associated with a decline in expression of two matricellular proteins thrombospondin 2 and tenascin C.
深入了解分娩过程对于预防早产至关重要，美国每年有 12.7%的婴儿会早产。宫颈重塑是这一过程的关键组成部分。从妊娠早期开始，重塑需要宫颈细胞外基质（ECM）的累积、渐进变化，导致胶原纤维结构的重新组织，同时逐渐丧失拉伸强度。在本研究中，我们对调节早期小鼠妊娠期间宫颈胶原结构的因素进行了详细的生化分析，包括参与原胶原加工、胶原纤维组装、交联形成以及 ECM 中胶原沉积的蛋白的表达。这些因素的变化与通过电子显微镜测量的胶原交联类型和胶原纤维的堆积的变化相关。在妊娠早期，两种细胞外基质蛋白（血小板反应蛋白 2 和 tenascin C）的表达下降，赖氨酰羟化酶的表达也下降，而赖氨酰羟化酶参与交联形成。这些变化伴随着 HP 和 LP 交联分别在妊娠第 12 天和第 14 天的下降，以及胶原纤维直径的逐渐增加。相比之下，胶原含量在整个妊娠过程中保持不变。我们得出结论，宫颈软化过程中拉伸强度的早期变化部分归因于胶原交联的数量和类型的变化，并与两种细胞外基质蛋白（血小板反应蛋白 2 和 tenascin C）的表达下降有关。
