Innervation of the rat uterus at estrus: a study in full-thickness, immunoperoxidase-stained whole-mount preparations.

The innervation of the nonpregnant rat uterus has been studied in histological sections, which contain only small samples of nerves and are unlikely to afford a complete picture of uterine innervation. Here we used whole-mount preparations of entire full-thickness uterine horns from nonpregnant rats in estrus to visualize autonomic or sensory nerves with peroxidase immunohistochemistry. Immunoreactivity was studied for tyrosine hydroxylase (TH)-labeled sympathetic nerves; vesicular acetylcholine transporter (VAChT), parasympathetic nerves; and substance P (SP) and calcitonin gene-related peptide (CGRP), sensory nerves. Neuropeptide Y (NPY) and nitric oxide synthase (NOS) identified more than one of these functionally distinct nerve types. Axons of all neurochemical classes entered the uterus at the mesometrium and innervated the uterine smooth muscle. The linea uteri, a dense band of longitudinal muscle opposite the mesometrium, contained more TH-, NPY-, CGRP-, and VAChT-immunoreactive axons than the remaining smooth muscle. Axons immunoreactive for NPY, SP, NOS, and VAChT formed a plexus near the circular muscle-endometrium interface. Rare TH- and NPY-immunoreactive axons and occasional CGRP-immunoreactive axons occurred close to uterine glands. Blood vessels had dense perivascular plexuses of TH- and NPY-containing axons and less dense NOS-, SP-, CGRP-, and VAChT-positive plexuses. The circular muscle plexus and glands were absent opposite the mesometrium. Uterine arterioles formed an interconnected network throughout the uterus. This article provides the first comprehensive description of the autonomic and sensory innervation of the nonpregnant rat uterus and will be a foundation for future studies on changes in uterine innervation caused by normal physiological or pathophysiological challenges.