Effects of Infantile/Prepubertal Chronic Estrogen Treatment and Chemical Sympathectomy with Guanethidine on Developing Cholinergic Nerves of the Rat Uterus

Abstract

(TC) S U M M A R Y The innervation of the uterus is remarkable in that it exhibits physiological changes in response to altered levels in the circulating levels of sex hormones. Previous studies by our group showed that chronic administration of estrogen to rats during the infantile/prepubertal period provoked, at 28 days of age, an almost complete loss of norepinephrine-labeled sympathetic nerves, similar to that observed in late pregnancy. It is not known, however, whether early exposure to estrogen affects uterine cholinergic nerves. Similarly, it is not known to what extent development and estrogen-induced responses in the uterine cholinergic innervation are affected by the absence of sympathetic nerves. To address this question, in this study we analyzed the effects of infantile/prepubertal chronic estrogen treatment, chronic chemical sympathectomy with guanethidine, and combined sympathectomy and chronic estrogen treatment on developing cholinergic nerves of the rat uterus. Cholinergic nerves were visualized using a combination of acetylcholinesterase histochemistry and the immunohistochemical demonstration of the vesicular acetylcholine transporter (VAChT). After chronic estrogen treatment, a well-developed plexus of cholinergic nerves was observed in the uterus. Quantitative studies showed that chronic exposure to estrogen induced contrasting responses in uterine cholinergic nerves, increasing the density of large and medium-sized nerve bundles and reducing the intercept density of fine fibers providing myometrial and perivascular innervation. Estrogen-induced changes in the uterine cholinergic innervation did not appear to result from the absence/impairment of sympathetic nerves, because sympathectomy did not mimic the effects produced by estrogen. Estrogen-induced responses in parasympathetic nerves are discussed, considering the direct effects of estrogen on neurons and on changes in neuron-target interactions.

Estrogen and female reproductive tract innervation: Cellular and molecular mechanisms of autonomic neuroplasticity

“…Following chronic estrogen treatment of immature rats, a robust cholinergic perivascular and myometrial plexus remains within the rat uterus (Richeri et al, 2002), thus confirming observations in the estrous cycle (Zoubina et al, 1998). A marked increase in the diameter of cholinergic bundles and nerve fibers is apparent at the end of treatment, and morphometric studies showed a rise in the density of large and medium-size cholinergic bundles.…”

The Autonomic Innervation and Uterine Telocyte Interplay in Leiomyoma Formation

“…Uterine autonomic innervation is influenced by hormonal regulation. Estrogens enhance the growth of UL and depress the development of uterine innervation (especially the sympathetic branch of the autonomic nervous system) [44][45][46] . TCs also express estrogen and progesterone receptors, which are specific for their localization.…”

Plasticity in developing rat uterine sensory nerves: the role of NGF and TrkA

“…Females were injected daily (Monday to Friday) with 50 mg/kg of guanethidine monosulphate (Sigma, USA) beginning the 8th day after birth and continuing for 3 weeks (Brauer et al 1994a;Richeri et al 2002). Guanethidine was dissolved to appropriate doses with 0.1 M phosphate buffer saline (PBS) and administrated subcutaneously.…”