title: Estrogen and female reproductive tract innervation: cellular and molecular mechanisms of autonomic neuroplasticity.
abstract: The female reproductive tract undergoes remarkable functional and structural changes associated with cycling, conception and pregnancy, and it is likely advantageous to both individual and species to alter relationships between reproductive tissues and innervation. For several decades, it has been appreciated that the mammalian uterus undergoes massive sympathetic axon depletion in late pregnancy, possibly representing an adaptation to promote smooth muscle quiescence and sustained blood flow. Innervation to other structures such as cervix and vagina also undergo pregnancy-related changes in innervation that may facilitate parturition. These tissues provide highly tractable models for examining cellular and molecular mechanisms underlying peripheral nervous system plasticity. Studies show that estrogen elicits rapid degeneration of sympathetic terminal axons in myometrium, which regenerate under low-estrogen conditions. Degeneration is mediated by the target tissue: under estrogen's influence, the myometrium produces proteins repulsive to sympathetic axons including BDNF, neurotrimin, semaphorins, and pro-NGF, and extracellular matrix components are remodeled. Interestingly, nerve depletion does not involve diminished levels of classical sympathetic neurotrophins that promote axon growth. Estrogen also affects sympathetic neuron neurotrophin receptor expression in ways that appear to favor pro-degenerative effects of the target tissue. In contrast to the uterus, estrogen depletes vaginal autonomic and nociceptive axons, with the latter driven in part by estrogen-induced suppression of BMP4 synthesis. These findings illustrate that hormonally mediated physiological plasticity is a highly complex phenomenon involving multiple, predominantly repulsive target-derived factors acting in concert to achieve rapid and selective reductions in innervation.
authors.affiliation: Laboratory of Cell Biology, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo 11600, Uruguay. Electronic address: brauer2009@gmail.com.
authors.forename: M
authors.initials: M
authors.lastname: Mónica Brauer
authors.affiliation: Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States; Institute for Neurological Discoveries, University of Kansas Medical Center, Kansas City, KS 66160, United States. Electronic address: psmith@kumc.edu.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Smith
mesh_terms: D000818:Animals; D001341:Autonomic Nervous System / Q000166:cytology* / Q000502:physiology*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005836:Genitalia, Female / Q000294:innervation*; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*
chemical_list: D004967:Estrogens
keywords: Estrogen; Female reproductive tract; Neuroplasticity; Parasympathetic nerves; Sensory nerves; Sympathetic nerves