The ovary of humans and nonhuman primates is innervated by sympathetic and sensory neurons of the peripheral nervous system. Recent studies demonstrated that the density of the sympathetic innervation to the rhesus monkey ovary is developmentally regulated, with adult density being attained around the time of puberty. In the present study, we used an immunocytochemical approach to obtain insights into the cell-cell signaling mechanisms that may contribute to the functional maintenance of this innervation. Because sympathetic neurons of the peripheral nervous system require target-derived neurotropins for their survival and function, experiments were conducted to determine if one of the receptors recognized by neurotropins is expressed in fibers innervating the primate ovary. A monoclonal antibody to the human low-affinity nerve growth factor (NGF) receptor, termed p75 NGFR because of its molecular weight, demonstrated the presence of this receptor in nerve fibers innervating the ovarian vasculature, interstitial tissue, and developing follicles of the gland. In addition, as shown in rodents, p75 NGFR immunoreactivity was detected in nonneuronal, endocrine cells of the ovary, specifically the thecal cell layer of developing follicles. Unexpectedly, however, the monkey ovary was also found to contain a network of small p75 NGFR immunoreactive cells distributed throughout the ovarian medulla and cortex. These cells, identified as such by confocal microscopy, had a neural-like appearance and displayed both neurofilament and neuron-specific enolase immunoreactivity. They appeared to be densely interconnected and were seen innervating the ovarian vasculature, the thecal cell layer of follicles, and, occasionally, primordial follicles. Double immunohistochemical procedures demonstrated that a subpopulation of these intraovarian, p75 NGFR-bearing neuron-like cells are catecholaminergic, as determined by their immunoreactivity to antibodies to tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis. RNA blot hybridization revealed the presence of p75 NGFR messenger RNA in the monkey ovary, thus demonstrating the ability of the gland to synthesize the receptors. These results demonstrate that the primate ovary contains an intrinsic network of neuron-like cells. Because such a neuronal network has not been detected in rodents or other non-primate species, it would appear that its presence in the primate ovary may have evolutionary significance.
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