Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, 10000 Prague, Czech Republic.
Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, 14700 Prague, Czech Republic.
Int J Mol Sci. 2021 Apr 14;22(8):4033. doi: 10.3390/ijms22084033.
This prospective cross-sectional case-control study investigated the postpartal gene expression of microRNAs associated with diabetes/cardiovascular/cerebrovascular diseases in the peripheral white blood cells of women with anamnesis of preterm prelabor rupture of membranes ( = 58), spontaneous preterm birth ( = 55), and term delivery ( = 89) by a quantitative reverse transcription polymerase chain reaction. After pregnancies complicated by preterm prelabor rupture of membranes or spontaneous preterm birth, mothers showed diverse expression profiles for 25 out of 29 tested microRNAs (miR-1-3p, miR-16-5p, miR-17-5p, miR-20a-5p, miR-20b-5p, miR-21-5p, miR-23a-3p, miR-24-3p, miR-26a-5p, miR-29a-3p, miR-100-5p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-130b-3p, miR-133a-3p, miR-143-3p, miR-145-5p, miR-146a-5p, miR-181a-5p, miR-195-5p, miR-199a-5p, miR-221-3p, miR-499a-5p, and miR-574-3p). The earliest gestational ages at delivery and the lowest birth weights of newborns were associated with the highest postpartal levels of the previously mentioned microRNAs in maternal peripheral white blood cells. Administration of tocolytic drugs in order to prolong pregnancy, used in order to administer and complete a full course of antenatal corticosteroids, was associated with alterations in postpartal microRNA expression profiles to a lesser extent than in women with imminent delivery, where there was insufficient time for administration of tocolytics and antenatal corticosteroids. Overall, mothers who did not receive tocolytic therapy (miR-24-3p and miR-146a-5p) and mothers who did not receive corticosteroid therapy (miR-1-3p, miR-100-5p, and miR-143-3p) had increased or showed a trend toward increased postpartal microRNA expression when compared with mothers given tocolytic and corticosteroid therapy. In addition, mothers with serum C-reactive protein levels above 20 mg/L, who experienced preterm labour, showed a trend toward increased postpartal expression profiles of miR-143-3p and miR-199a-5p when compared with mothers with normal serum C-reactive protein levels. On the other hand, the occurrence of maternal leukocytosis, the presence of intra-amniotic inflammation (higher levels of interleukin 6 in the amniotic fluid), and the administration of antibiotics at the time of preterm delivery had no impact on postpartal microRNA expression profiles in mothers with a history of preterm delivery. Likewise, the condition of the newborns at the moment of birth, determined by Apgar scores at 5 and 10 min and the pH of cord arterial blood, had no influence on the postpartal expression profiles of mothers with a history of preterm delivery. These findings may contribute to explaining the increased cardiovascular risk in mothers with anamnesis of preterm delivery, and the greater increase of maternal cardiovascular risk with the decrease of gestational age at delivery. Women with preterm delivery in their anamnesis represent a high-risk group with special needs on a long-term basis, with a need to apply preventive and therapeutic interventions as early as possible.
这项前瞻性病例对照研究通过定量逆转录聚合酶链反应,调查了有早产胎膜早破病史(=58)、自发性早产(=55)和足月分娩(=89)的妇女分娩后外周血白细胞中与糖尿病/心血管/脑血管疾病相关的 microRNAs 的产后基因表达。在早产胎膜早破或自发性早产的妊娠后,母亲的 29 个 microRNA 中有 25 个表现出不同的表达谱(miR-1-3p、miR-16-5p、miR-17-5p、miR-20a-5p、miR-20b-5p、miR-21-5p、miR-23a-3p、miR-24-3p、miR-26a-5p、miR-29a-3p、miR-100-5p、miR-103a-3p、miR-125b-5p、miR-126-3p、miR-130b-3p、miR-133a-3p、miR-143-3p、miR-145-5p、miR-146a-5p、miR-181a-5p、miR-195-5p、miR-199a-5p、miR-221-3p、miR-499a-5p 和 miR-574-3p)。分娩时最早的胎龄和新生儿的最低出生体重与母体外周血白细胞中上述 microRNAs 的最高产后水平相关。为延长妊娠而使用的保胎药物,以及为完成全程产前皮质类固醇治疗而使用的药物,与即将分娩的妇女相比,对产后 microRNA 表达谱的影响较小,因为在即将分娩的妇女中,没有足够的时间使用保胎药物和产前皮质类固醇。总的来说,未接受保胎治疗的母亲(miR-24-3p 和 miR-146a-5p)和未接受皮质类固醇治疗的母亲(miR-1-3p、miR-100-5p 和 miR-143-3p)的产后 microRNA 表达水平增加或呈增加趋势,与接受保胎和皮质类固醇治疗的母亲相比。此外,血清 C 反应蛋白水平高于 20mg/L 的母亲,经历早产,与血清 C 反应蛋白水平正常的母亲相比,产后 miR-143-3p 和 miR-199a-5p 的表达谱呈增加趋势。另一方面,产妇白细胞增多、羊水内存在宫内炎症(羊水中白细胞介素 6 水平升高)以及在早产时使用抗生素,对有早产史的母亲产后 microRNA 表达谱没有影响。同样,新生儿在出生时的状况,通过 5 分钟和 10 分钟时的 Apgar 评分和脐动脉血的 pH 值来确定,对有早产史的母亲的产后表达谱没有影响。这些发现可能有助于解释有早产史的母亲心血管风险增加的原因,以及分娩时胎龄越小,母亲心血管风险增加的幅度越大。有早产史的妇女代表了一个高风险群体,需要长期的特殊需求,需要尽早应用预防性和治疗性干预措施。