Variations in uterine innervation during the estrous cycle in rat

Abstract

Uterine innervation undergoes profound remodeling during puberty, pregnancy, and after parturition. However, the extent to which uterine innervation may change during the estrous cycle is uncertain. The objective of the present study was to determine whether nerve fiber density of the uterine horn is altered during the estrous cycle and, if so, which subpopulations are affected. Immunostaining for the pan-neuronal marker protein gene product (PGP) 9.5 revealed fibers within the vascular zone, myometrium, and endometrium, with greater density in the ovarian and cervical regions than in the middle. In most structures, nerve density was reduced during estrus. This could not be accounted for by increased target volume, as the reduction in longitudinal muscle innervation persisted after correction for changes in target size. Immunostaining for vasoactive intestinal polypeptide-immunoreactive parasympathetic nerves revealed fibers associated predominantly with the vascular zone and circular muscle within the cervical region. No cyclical variation was detected. Calcitonin gene-related peptide-immunoreactive nerves were present within all structures, and density was highest at the ovarian end. These fibers also did not vary significantly through estrous. Dopamine beta-hydroxylase-immunoreactive sympathetic nerves innervated all structures, with greater density in the ovarian end. These fibers were reduced substantially during estrus, but the decline was also significant in proestrus, thus preceding that detected by using the pan-neuronal marker. We conclude that the estrous cycle in rat is accompanied by structural remodeling of sympathetic nerves by way of retraction or degeneration of terminal fibers during estrus. The structural loss of the terminal axon apparently is preceded by depletion of catecholamine-synthesizing enzyme.

Differential effects of oestrogen on developing and mature uterine sympathetic nerves

“…The results reported in this paper regarding the distribution and regional variations of sympathetic nerves in the prepubertal rat uterus are in agreement with previous findings in the immature and cycling rat (Papka et al 1985;Brauer et al 1992;Melo and Machado 1993;Houdeau et al 1998;Zoubina et al 1998). …”

“…In addition, intensely fluorescent enlargements suggesting nerve degeneration have occasionally been recognised in both myometrial and perivascular locations. In line with this concept, recent studies in the adult rat have shown that during the natural oestrous cycle, the density of dopamine-beta-hydroxylase-positive nerves decreases at proestrus and oestrus and increases at dioestrus (Zoubina et al 1998). Electronmicroscopic studies (Zoubina and Smith 2000) indicate that these changes are related to cycles of degeneration and regeneration of terminal axons.…”

“…In the uterine horn, the density of NA-L myometrial fibres was assessed in the longitudinal myometrial layer by using the method reported by Zoubina et al (1998) with minor modifications. Nerve counting was carried out on two transverse cryostat section of the cephalic, middle and caudal region of the uterine horn per animal.…”

“…Sex-hormone induced plasticity of uterine sympathetic nerves includes a complete degeneration of perivascular and myometrial innervation during pregnancy (Thorbert administration of sex hormones have been unsuccessful Malcolm 1978, 1988). In addition to pregnancy-induced changes, the sympathetic innervation of the uterus undergoes a partial remodelling during puberty (Brauer et al 1992) and the oestrous cycle (Adham and Schenk 1969;Marshall 1981;Melo and Machado 1993;Zoubina et al 1998) but this only involves the myometrial-associated sympathetic innervation. Although the contribution of progesterone to these changes remains uncertain, there is increasing evidence that oestrogen is a key factor in the remodelling of uterine sympathetic nerves in the non-pregnant female (Brauer et al 1995(Brauer et al , 1999).…”

Impaired cutaneous wound healing after sensory denervation in developing rats: effects on cell proliferation and apoptosis

“…To assess the frequency of occurrence of CGRP-immunoreactive nerves and α-SMA-immunoreactive cell cytoplasm, a stereology grid with line intersections at 25-µm intervals was superimposed upon the digitized images (NIH Image), and the number of intersections over immunoreactive structures was divided by the total number of intersections over the entire field to provide an index of the apparent percentage area occupied by immunoreactive structures (Liu et al 1999;Zoubina et al 1998). To provide an index of wound tissue volume occupied by myofibroblasts, the percentage α-SMA-immunoreactive sectional area was multiplied by total wound volume.…”