Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats

Functional and histochemical characterization of a uterine adrenergic denervation process in pregnant rats
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DOI:
10.1095/biolreprod.101.002287
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发表时间:
2002-09-01
影响因子:
3.6
通讯作者:
Falkay, G
Falkay, G
中科院分区:
生物学2区
文献类型:
--
作者:
Klukovits, A;Gáspár, R;Falkay, G

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采用电场刺激和组织荧光技术分别观察了6-羟多巴胺处理大鼠和正常大鼠妊娠期子宫环收缩反应和交感神经支配模式的变化。在未怀孕、6-羟多巴胺处理和怀孕5、10、15、18和22天(足月)大鼠的子宫制剂中,测量了电场刺激(0.6 msec, 1-70 Hz, 40 V)引起的神经介导的收缩。在所有频率中,未怀孕子宫的收缩幅度最高。1-2.5 Hz的刺激诱发了妊娠10天子宫的收缩,但在第5天和第15天以后没有引起子宫收缩。在足月和6-羟多巴胺处理大鼠的子宫制剂中,1-20 Hz的刺激不能引起收缩。子宫肾上腺素能神经荧光组化结果显示,妊娠和非妊娠大鼠血管周围和子宫肌层神经分布丰富。到第15天,肾上腺素能神经纤维变性和丢失明显,到第22天,荧光肌和血管周围神经几乎消失。这些发现表明,从妊娠中期开始,神经介导的子宫收缩出现了进行性、频率相关的减少,同时肾上腺素能神经纤维逐渐丧失。妊娠引起的神经变性可促进非突触-肾上腺素能性子宫收缩活动的发展。妊娠早期子宫平滑肌对电场刺激的反应性降低似乎与子宫神经支配的改变无关,但可能与植入相关的变化有关。
The time course of pregnancy-induced changes in the contractile responses of isolated uterine rings and sympathetic innervation pattern were studied using electric field stimulation and histofluorescence techniques, respectively, in intact and 6-hydroxydopamine-treated rats. Neurally mediated contractions elicited by field stimulation (0.6 msec, 1-70 Hz, 40 V) were measured in uterine preparations obtained from nonpregnant, 6-hydroxydopamine-treated and 5-, 10-, 15-, 18-, and 22-day (term) pregnant rats. At all frequencies, the amplitudes of contractions were highest in nonpregnant uteri. Stimulation at 1-2.5 Hz evoked contractions in 10-day pregnant uteri but failed to cause contractions on Day 5 and from Day 15 onward. In uterine preparations obtained from term and from 6-hydroxydopamine-treated rats, contractions could not be evoked by stimulation at 1-20 Hz. Fluorescence histochemistry of uterine adrenergic nerves revealed rich perivascular and myometrial innervation in nonpregnant and in pregnant rats through Day 10. Degeneration and loss of adrenergic nerve fibers was apparent by Day 15, and fluorescent myometrial and perivascular nerves were practically absent by Day 22. These findings demonstrate a progressive, frequency-related reduction of nerve-mediated uterine contractions beginning in midterm pregnancy, in parallel with a gradual loss of adrenergic nerve fibers. Pregnancy-induced nerve degeneration may promote the development of nonsynaptic alpha-adrenergic uterine contractile activity towards term. The reduced responsiveness of uterine smooth muscle to electric field stimulation in early pregnancy appears to be unrelated to alterations in uterine innervation but may be related to changes associated with implantation.