Elmes Matthew, Szyszka Alexandra, Pauliat Caroline, Clifford Bethan, Daniel Zoe, Cheng Zhangrui, Wathes Claire, McMullen Sarah
Division of Nutritional Sciences, University of Nottingham, Loughborough, UK
Division of Nutritional Sciences, University of Nottingham, Loughborough, UK.
Physiol Rep. 2015 Apr;3(4). doi: 10.14814/phy2.12305.
Advanced maternal age of first time pregnant mothers is associated with prolonged and dysfunctional labor and significant risk of emergency cesarean section. We investigated the influence of maternal age on myometrial contractility, expression of contractile associated proteins (CAPs), and global gene expression in the parturient uterus. Female Wistar rats either 8 (YOUNG n = 10) or 24 (OLDER n = 10) weeks old were fed laboratory chow, mated, and killed during parturition. Myometrial strips were dissected to determine contractile activity, cholesterol (CHOL) and triglycerides (TAG) content, protein expression of connexin-43 (GJA1), prostaglandin-endoperoxide synthase 2 (PTGS2), and caveolin 1 (CAV-1). Maternal plasma concentrations of prostaglandins PGE2, PGF2α, and progesterone were determined by RIA. Global gene expression in uterine samples was compared using Affymetrix Genechip Gene 2.0 ST arrays and Ingenuity Pathway analysis (IPA). Spontaneous contractility in myometrium exhibited by YOUNG rats was threefold greater than OLDER animals (P < 0.027) but maternal age had no significant effect on myometrial CAP expression, lipid profiles, or pregnancy-related hormones. OLDER myometrium increased contractile activity in response to PGF2α, phenylephrine, and carbachol, a response absent in YOUNG rats (all P < 0.002). Microarray analysis identified that maternal age affected expression of genes related to immune and inflammatory responses, lipid transport and metabolism, steroid metabolism, tissue remodeling, and smooth muscle contraction. In conclusion YOUNG laboring rat myometrium seems primed to contract maximally, whereas activity is blunted in OLDER animals and requires stimulation to meet contractile potential. Further work investigating maternal age effects on myometrial function is required with focus on lipid metabolism and inflammatory pathways.
初产妇的高龄与产程延长和功能失调以及紧急剖宫产的重大风险相关。我们研究了产妇年龄对产妇子宫肌层收缩性、收缩相关蛋白（CAPs）表达以及整体基因表达的影响。将8周龄（年轻组，n = 10）或24周龄（年长组，n = 10）的雌性Wistar大鼠喂食实验室饲料，进行交配，并在分娩期间处死。解剖子宫肌条以确定收缩活性、胆固醇（CHOL）和甘油三酯（TAG）含量、连接蛋白43（GJA1）、前列腺素内过氧化物合酶2（PTGS2）和小窝蛋白1（CAV - 1）的蛋白表达。通过放射免疫分析法测定母体血浆中前列腺素PGE2、PGF2α和孕酮的浓度。使用Affymetrix Genechip Gene 2.0 ST阵列和 Ingenuity Pathway分析（IPA）比较子宫样本中的整体基因表达。年轻大鼠子宫肌层的自发收缩性比年长动物高三倍（P < 0.027），但产妇年龄对子宫肌层CAP表达、脂质谱或妊娠相关激素没有显著影响。年长大鼠的子宫肌层对PGF2α、去氧肾上腺素和卡巴胆碱的反应增加了收缩活性，而年轻大鼠没有这种反应（所有P < 0.002）。微阵列分析确定产妇年龄影响与免疫和炎症反应、脂质转运和代谢、类固醇代谢、组织重塑和平滑肌收缩相关的基因表达。总之，年轻分娩大鼠的子宫肌层似乎已准备好最大限度地收缩，而年长动物的活性则减弱，需要刺激才能达到收缩潜力。需要进一步研究产妇年龄对子宫肌层功能的影响，重点关注脂质代谢和炎症途径。
