ABSTRACT
In our previous study, preterm birth after pre-pregnancy partial cervical excision demonstrated abnormal wound healing with an increased muscle-to-collagen ratio at the proximal site of the cervix. We aimed to investigate whether treatment with plasma fibronectin affects the differentiation of mouse uterine cervical fibroblasts into myofibroblasts and mediates a reduction in the incidence of preterm delivery in mice. We examined the gestational period after the administration of lipopolysaccharide in mice subjected to cervical excision and subsequently treated with fibronectin or vehicle. We confirmed that the gestational period was longer in the plasma fibronectin-treated group than in the vehicle-treated control group. In addition, the ratio of α-smooth muscle actin to collagen type I alpha 1 increased after LPS injection in mice subjected to cervical excision, and this increase was suppressed by plasma fibronectin treatment. Plasma fibronectin may serve as a potential therapeutic agent to prevent preterm delivery by inhibiting myogenic differentiation in the cervix.
Subject(s)
Cervix Uteri , Premature Birth , Animals , Cervix Uteri/surgery , Female , Fibronectins , Humans , Infant, Newborn , Inflammation , Lipopolysaccharides , Mice , PregnancyABSTRACT
We investigated changes in gene expression of cervical collagens, matrix metalloproteinases (MMPs), and tissue inhibitors of metalloproteinases (TIMPs) during pre-gestational uterine cervical excision and/or inflammation-induced preterm labor in mice. Forty sexually mature female mice were uniformly divided into four groups: sham, cervical excision, lipopolysaccharide (LPS) injection, and cervical excision plus LPS injection. Partial cervical tissue excision was performed at five weeks of age before mating. LPS was injected into the lower right uterine horn near the cervix on gestational day 16. Mice were sacrificed immediately postpartum. Uterine cervices were collected and subjected to quantitative real-time PCR. Col4α1 and Col5α1 expression increased significantly in the cervical excision plus LPS injection group compared to the sham group (p < 0.01 and p = 0.024, respectively). MMP-14 expression levels increased in the cervical excision plus LPS injection group compared to the sham group (p < 0.01). TIMP-1 expression was not significantly decreased in this group. Increased expression levels of Col4α1, Col5α1, and MMP-14 were associated with cervical excision plus inflammation-induced preterm labor. Thus, pre-gestational cervical remodeling through specific collagen metabolism and MMP activation may involve the pathogenesis of spontaneous preterm labor.
Subject(s)
Cervix Uteri/metabolism , Obstetric Labor, Premature/genetics , Animals , Cervix Uteri/physiology , Collagen/genetics , Female , Gene Expression/genetics , Gene Expression Profiling/methods , Gene Expression Regulation/genetics , Labor, Induced/methods , Matrix Metalloproteinases/genetics , Mice , Mice, Inbred C57BL , Pregnancy , Tissue Inhibitor of Metalloproteinases/genetics , Transcriptome/genetics , Uterus/metabolismABSTRACT
Preterm labor and birth are the primary causes of neonatal morbidities and mortalities. The early detection and treatment of preterm uterine muscular contraction are crucial for the management of preterm labor. In this work, a ring electrode with a wireless electrical recording and stimulating (RE-WERS) system was designed, fabricated, and investigated for the non-invasive monitoring of uterine contraction/relaxation as a diagnostic and therapeutic tool for preterm labor. By using an organ bath system, we confirmed that the uterine contraction force in mice can be decreased by the application of electrical stimulation. Then, the RE-WERS system was inserted non-invasively through the vagina to the cervix of a pregnant minipig, and it successfully recorded the uterine contraction and reflect signals when various electrical stimulating conditions were applied. The difference in the uterine signals before and after the injection of a labor induction drug, such as oxytocin and prostaglandin [Formula: see text], was recorded, and the difference was remarkable. In addition, the uterine signal that was recorded was well matched with the signal of the electromyography (EMG) kit during open abdominal surgery. It seemed that the continuous and various electrical stimulations affected the delay or inhibition of childbirth in the pregnant minipig.
