Abstract：
Animal models have been developed to aid understanding of the increased incidence of adverse pregnancy complications observed in women of advanced maternal age (AMA). This systematic review of murine models of AMA demonstrates consistent effects of decreased litter size and fetal weight; this supports the future use of these models to determine pathophysiological mechanisms and test therapeutic strategies to improve poor pregnancy outcomes in AMA.
Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.
Advanced maternal age (AMA; ≥35 years of age) is associated with an increased risk of adverse pregnancy outcomes. To explore causes of adverse pregnancy outcomes in AMA, and to test candidate therapies, an increasing number of murine AMA models have been developed. The aim of this study was to systematically review the literature to assess whether murine AMA models demonstrate a reproducible effect on pregnancy outcomes. PubMed, Ovid, Web of Science and Google Scholar were searched. Studies that reported on pregnancy outcomes in AMA mice and rats were included; the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool evaluated the risk of bias. Eleven mouse and six rat studies were included. AMA mice and rats had reduced litter size (standardised mean difference (SMD): -1.59, 95% confidence interval (CI): -1.84, -1.34 for mice; SMD: -1.66, 95% (CI): -2.09, -1.23 for rats) and reduced fetal weight (SMD: -0.87, 95% CI: -1.24, -0.49 for mice; SMD: -1.05, 95% CI: -1.40, -0.69 for rats). Placental weight was increased in AMA mice (SMD: 0.62, 95% CI: 0.16, 1.08). Subgroup analysis indicated that C57Bl/6 mice had less heterogeneity than other, mostly outbred, mouse strains with regards to litter size (C57 strain I2 = 68.2% vs other strain types I2 = 85.7%). The risk of bias was high, mostly due to the lack of methodological detail and unclear reporting of findings. Murine models of AMA demonstrate similar adverse pregnancy outcomes to those observed in large human epidemiological studies. The reproducible phenotypes in AMA murine models allow the exploration of mechanisms underpinning poor pregnancy outcomes and the pursuit of therapeutic interventions.
摘要：
高龄产妇年龄（AMA；≥35岁）与不良妊娠结局的风险增加相关。探讨AMA不良妊娠结局的原因,并测试候选疗法，越来越多的鼠AMA模型已被开发。这项研究的目的是系统地回顾文献，以评估鼠AMA模型是否对妊娠结局具有可重复的作用。PubMed,奥维德,搜索了WebofScience和GoogleScholar。包括报道AMA小鼠和大鼠妊娠结局的研究；SYRCLE工具评估了偏倚的风险。包括11只小鼠和6只大鼠研究。AMA小鼠和大鼠产仔数减少（小鼠的标准化平均差（SMD）-1.59，95％CI-1.84，-1.34；大鼠的SMD-1.66，95％置信区间（CI）-2.09，-1.23），胎儿体重降低（小鼠的SMD-0.87，95％CI-1.24，-0.49；大鼠的SMD-1.05，95％CI-1.40，0.40。AMA小鼠的胎盘重量增加（SMD0.62，95％CI0.16，1.08）。亚组分析表明，C57Bl/6小鼠的异质性较小，大多是远交的，关于产仔数的小鼠品系（C57品系I2=68.2％，其他品系I2=85.7％）。偏见的风险很高，主要是由于缺乏方法细节和不清楚的结果报告。AMA的鼠模型显示与大型人类流行病学研究中观察到的不良妊娠结局相似。AMA小鼠模型中的可重复表型允许探索支持不良妊娠结局和追求治疗干预的机制。
