Effect of reproductive ageing on pregnant mouse uterus and cervix.
Effect of reproductive ageing on pregnant mouse uterus and cervix.
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DOI：
10.1113/jp273350
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发表时间：
2017-03-15
期刊：
影响因子：
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通讯作者：
Tribe RM
中科院分区：
文献类型：
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作者：
Patel R;Moffatt JD;Mourmoura E;Demaison L;Seed PT;Poston L;Tribe RM
年龄较大的孕妇有更大的手术分娩，死产和后期诱导的风险。这表明母亲的年龄可以影响分娩的时间和分娩过程。我们发现，增加母亲的年龄在C57 BL/6J小鼠与妊娠期延长和劳动长度。年龄较大的怀孕小鼠也有延迟的孕酮戒断和子宫肌层功能受损。子宫老化和劳动力功能障碍应进一步调查在老年早孕妇女。高龄产妇（≥ 35岁）与手术分娩、死产和足月引产率增加相关。生理原因仍然不确定，虽然受损的子宫肌层功能已牵连。为了研究母体年龄直接影响成功分娩的假设，我们使用红外视频记录评估了3个月（年轻）和5个月（中间）与8个月（更大）的妊娠C57 BL/6J小鼠的出生时间和胎儿结局。同时检测血清孕酮水平、子宫肌层和宫颈功能以及线粒体电子传递链复合酶活性。与3月龄小鼠相比，年龄较大的妊娠小鼠的平均妊娠期和分娩持续时间较长（P <0.001），窝仔数减少（P <0.01）。老年小鼠血清孕酮浓度没有表现出与年轻小鼠相同的下降。老龄小鼠的宫颈组织比青年小鼠的扩张更大（P <0.05）。与3月龄小鼠相比，8月龄小鼠子宫肌层中催产素受体和连接蛋白-43 mRNA表达降低（分别为P <0.05和P <0.01），同时子宫肌层自发收缩频率更高但持续时间更短（P <0.05），对催产素的收缩反应减弱。老年小鼠子宫肌层线粒体拷贝数减少，尽管线粒体电子传递链复合物的酶活性没有年龄诱导的变化。总之，8个月大的小鼠提供了一个有用的生殖衰老模型。目前的研究已经确定了劳动功能障碍的潜在原因，适合调查在老年早孕妇女。年龄较大的孕妇有更大的手术分娩，死产和后期诱导的风险。这表明母亲的年龄可以影响分娩的时间和分娩过程。我们发现，增加母亲的年龄在C57 BL/6J小鼠与妊娠期延长和劳动长度。年长的怀孕小鼠还出现黄体酮撤退延迟和子宫肌层功能受损。子宫老化和劳动力功能障碍应进一步调查在老年早孕妇女。
Older pregnant women have a greater risk of operative delivery, still birth and post‐term induction. This suggests that maternal age can influence the timing of birth and processes of parturition. We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour. Older pregnant mice also had delayed progesterone withdrawal and impaired myometrial function. Uterine ageing and labour dysfunction should be investigated further in older primigravid women. Advanced maternal age (≥35 years) is associated with increased rates of operative delivery, stillbirth and post‐term labour induction. The physiological causes remain uncertain, although impaired myometrial function has been implicated. To investigate the hypothesis that maternal age directly influences successful parturition, we assessed the timing of birth and fetal outcome in pregnant C57BL/6J mice at 3 months (young) and 5 months (intermediate) vs. 8 months (older) of age using infrared video recording. Serum progesterone profiles, myometrium and cervix function, and mitochondrial electron transport chain complex enzymatic activities were also examined. Older pregnant mice had a longer mean gestation and labour duration (P < 0.001), as well as reduced litter size (P < 0.01) vs. 3‐month‐old mice. Older mice did not exhibit the same decline in serum progesterone concentrations as younger mice. Cervical tissues from older mice were more distensible than younger mice (P < 0.05). Oxytocin receptor and connexin‐43 mRNA expression were reduced in the myometrium from 8‐month‐old vs. 3‐month‐old mice (P < 0.05 and P < 0.01 respectively) in tandem with more frequent but shorter duration spontaneous myometrial contractions (P < 0.05) and an attenuated contractile response to oxytocin. Myometrial mitochondrial copy number was reduced in older mice, although there were no age‐induced changes to the enzymatic activities of the mitochondrial electron transport chain complexes. In conclusion, 8‐month‐old mice provide a useful model of reproductive ageing. The present study has identified potential causes of labour dysfunction amenable to investigation in older primigravid women. Older pregnant women have a greater risk of operative delivery, still birth and post‐term induction. This suggests that maternal age can influence the timing of birth and processes of parturition. We have found that increasing maternal age in C57BL/6J mice is associated with prolongation of gestation and length of labour. Older pregnant mice also had delayed progesterone withdrawal and impaired myometrial function. Uterine ageing and labour dysfunction should be investigated further in older primigravid women.