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Biology of Reproduction 67, 1013-1017 (2002)
© 2002 Society for the Study of Reproduction, Inc.


Regular Article

Functional and Histochemical Characterization of a Uterine Adrenergic Denervation Process in Pregnant Rats1

Anna Klukovitsa, Róbert Gáspára, Péter Sánthab, Gábor Jancsób, and George Falkay2,,a

a Department of Pharmacodynamics and Biopharmacy, University of Szeged, 6720 Szeged, Hungary b Department of Physiology, University of Szeged, 6720 Szeged, Hungary

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.

First decision: 29 December 2001.

1 This work was supported by Hungarian Research grants OTKA T033126 and T032507.

2 Correspondence: George Falkay, Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. FAX: 36 62 545 567; falkay{at}pharma.szote.u-szeged.hu




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