Department of Obstetrics and Gynecology, Korea University College of Medicine, Seoul, Korea.
Department of Pediatrics, Ansan Hospital, Korea University College of Medicine, Ansan, Korea.
PLoS One. 2021 Apr 14;16(4):e0250108. doi: 10.1371/journal.pone.0250108. eCollection 2021.
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.
我们研究了在妊娠前子宫颈切除和/或炎症诱导的早产中,小鼠宫颈胶原、基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制剂(TIMPs)的基因表达变化。将 40 只性成熟雌性小鼠均匀分为四组:假手术组、宫颈切除组、脂多糖(LPS)注射组和宫颈切除加 LPS 注射组。在交配前 5 周进行部分宫颈组织切除。在妊娠第 16 天,将 LPS 注入宫颈附近的右下子宫角。产后立即处死小鼠。收集子宫颈并进行实时定量 PCR。与假手术组相比,宫颈切除加 LPS 注射组的 Col4α1 和 Col5α1 表达显著增加(p<0.01 和 p=0.024)。与假手术组相比,宫颈切除加 LPS 注射组的 MMP-14 表达水平增加(p<0.01)。该组中 TIMP-1 的表达没有明显降低。Col4α1、Col5α1 和 MMP-14 的表达水平升高与宫颈切除加炎症诱导的早产有关。因此,妊娠前通过特定的胶原代谢和 MMP 激活进行的宫颈重塑可能涉及自发性早产的发病机制。