Background

The intrinsic properties of pelvic soft tissues in women who do and do not sustain birth injuries are likely divergent. However, little is known about this. Rat pelvic floor muscles undergo protective pregnancy-induced structural adaptations-sarcomerogenesis and increase in intramuscular collagen content-that protect against birth injury.

Objective

We aimed to test the following hypotheses: (1) the increased mechanical load of a gravid uterus drives antepartum adaptations; (2) load-induced changes are sufficient to protect pelvic muscles from birth injury.

Study Design

The independent effects of load uncoupled from the hormonal milieu of pregnancy were tested in 3- to 4-month-old Sprague-Dawley rats randomly divided into the following 4 groups, with N of 5 to 14 per group: (1) load⁻/pregnancy hormones⁻ (controls), (2) load⁺/pregnancy hormones⁻, (3) reduced load/pregnancy hormones⁺, and (4) load⁺/pregnancy hormones⁺. Mechanical load of a gravid uterus was simulated by weighing uterine horns with beads similar to fetal rat size and weight. A reduced load was achieved by unilateral pregnancy after unilateral uterine horn ligation. To assess the acute and chronic phases required for sarcomerogenesis, the rats were sacrificed at 4 hours or 21 days after bead loading. The coccygeus, iliocaudalis, pubocaudalis, and nonpelvic tibialis anterior musles were harvested for myofiber and sarcomere length measurements. The intramuscular collagen content was assessed using a hydroxyproline assay. An additional 20 load⁺/pregnancy hormones⁻ rats underwent vaginal distention to determine whether the load-induced changes are sufficient to protect from mechanical muscle injury in response to parturition-associated strains of various magnitude. The data, compared using 2-way repeated measures analysis of variance followed by pairwise comparisons, are presented as mean±standard error of mean.

Results

An acute increase in load resulted in significant pelvic floor muscle stretch, accompanied by an acute increase in sarcomere length compared with nonloaded control muscles (coccygeus: 2.69±0.03 vs 2.30±0.06 μm, respectively, P<.001; pubocaudalis: 2.71±0.04 vs 2.25±0.03 μm, respectively, P<.0001; and iliocaudalis: 2.80±0.06 vs 2.35±0.04 μm, respectively, P<.0001). After 21 days of sustained load, the sarcomeres returned to operational length in all pelvic muscles (P>.05). However, the myofibers remained significantly longer in the load⁺/pregnancy hormones⁻ than the load⁻/pregnancy hormones⁻ in coccygeus (13.33±0.94 vs 9.97±0.26 mm, respectively, P<.0001) and pubocaudalis (21.20±0.52 vs 19.52±0.34 mm, respectively, P<.04) and not different from load⁺/pregnancy hormones⁺ (12.82±0.30 and 22.53±0.32 mm, respectively, P>.1), indicating that sustained load-induced sarcomerogenesis in these muscles. The intramuscular collagen content in the load⁺/pregnancy hormones⁻ group was significantly greater relative to the controls in coccygeus (6.55±0.85 vs 3.11±0.47 μg/mg, respectively, P<.001) and pubocaudalis (5.93±0.79 vs 3.46±0.52 μg/mg, respectively, P<.05) and not different from load⁺/pregnancy hormones⁺ (7.45±0.65 and 6.05±0.62 μg/mg, respectively, P>.5). The iliocaudalis required both mechanical and endocrine cues for sarcomerogenesis. The tibialis anterior was not affected by mechanical or endocrine alterations. Despite an equivalent extent of adaptations, load-induced changes were only partially protective against sarcomere hyperelongation.

Conclusion

Load induces plasticity of the intrinsic pelvic floor muscle components, which renders protection against mechanical birth injury. The protective effect, which varies between the individual muscles and strain magnitudes, is further augmented by the presence of pregnancy hormones. Maximizing the impact of mechanical load on the pelvic floor muscles during pregnancy, such as with specialized pelvic floor muscle stretching regimens, is a potentially actionable target for augmenting pregnancy-induced adaptations to decrease birth injury in women who may otherwise have incomplete antepartum muscle adaptations.

中文翻译：

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大鼠临床前模型中保护性妊娠诱导的盆底肌肉适应的机制

背景

遭受和未遭受产伤的女性盆腔软组织的内在特性可能有所不同。然而，人们对此知之甚少。大鼠盆底肌肉经历保护性妊娠诱导的结构适应——肌瘤生成和肌内胶原蛋白含量增加——从而防止产伤。

客观的

我们的目的是检验以下假设：（1）妊娠子宫机械负荷的增加驱动产前适应；(2)负荷引起的变化足以保护骨盆肌肉免受出生损伤。

学习规划

在 3 至 4 个月大的 Sprague-Dawley 大鼠中测试了与妊娠激素环境无关的负荷的独立影响，随机分为以下 4 组，每组 N 为 5 至 14：(1) 负荷^- /妊娠激素^-（对照），(2) 负荷⁺ /妊娠激素^-，(3) 减少负荷/妊娠激素⁺，和 (4) 负荷⁺ /妊娠激素⁺。通过用与胎鼠大小和重量相似的珠子称量子宫角来模拟妊娠子宫的机械负荷。单侧子宫角结扎后单侧妊娠可减轻负荷。为了评估肌瘤形成所需的急性和慢性阶段，在珠加载后4小时或21天处死大鼠。收获尾骨、髂尾肌、耻骨尾肌和非骨盆胫骨前肌用于肌纤维和肌节长度测量。使用羟脯氨酸测定法评估肌内胶原蛋白含量。另外20种负荷⁺ /妊娠激素^-大鼠接受阴道扩张，以确定负荷引起的变化是否足以防止机械性肌肉损伤，以响应不同程度的分娩相关应变。使用双向重复测量方差分析进行比较，然后进行成对比较，将数据表示为平均值±平均值的标准误差。

结果

负荷的急剧增加导致盆底肌肉显着拉伸，同时与未负荷的对照肌肉相比，肌节长度急剧增加（尾骨：分别为 2.69±0.03 与 2.30±0.06 μm，P <.001；耻尾肌：2.71 ± 0.04分别为 2.25±0.03 μm，P <.0001；髂尾肌：分别为 2.80±0.06 vs 2.35±0.04 μm，P <.0001）。经过 21 天的持续负荷后，所有骨盆肌肉的肌节恢复到工作长度 ( P >.05)。^{然而，尾骨肌（分别为 13.33±0.94 与9.97} ±0.26 毫米，P <.0001）和耻尾肌（21.20±0.52 与 19.52）^{中，负荷 + /妊娠激素 -}的^肌纤维仍然^显着更长。±0.34 mm，分别，P <.04）并且与负荷⁺ /妊娠激素⁺没有不同（分别为12.82±0.30和22.53±0.32 mm，P >.1），表明这些肌肉中持续负荷诱导的肌瘤生成。负荷⁺ /妊娠激素^{-组中尾骨肌（分别为6.55±0.85 vs 3.11±0.47 μg/mg，} P <.001）和耻尾肌（5.93±0.79 vs 3.46±）的肌内胶原蛋白含量显着高于对照组。分别为 0.52 μg/mg，P <.05)，与负荷⁺ /妊娠激素⁺没有差异（分别为 7.45±0.65 和 6.05±0.62 μg/mg，P >.5）。髂尾肌的肌瘤生成需要机械和内分泌信号。胫骨前肌不受机械或内分泌改变的影响。尽管适应程度相当，但负荷引起的变化只能部分防止肌节过度伸长。

结论

负荷会引起盆底肌肉内在成分的可塑性，从而防止机械性分娩损伤。保护作用因个体肌肉和应变大小而异，怀孕激素的存在进一步增强了保护作用。最大限度地提高怀孕期间机械负荷对盆底肌肉的影响，例如采用专门的盆底肌肉拉伸方案，是增强妊娠引起的适应以减少产前肌肉适应不完整的女性产伤的潜在可行目标。