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Expression of Nerve Growth Factor (NGF) Isoforms in the Rat Uterus during Pregnancy: Accumulation of Precursor proNGF

Institute of Anatomy, University of Leipzig, Leipzig D-04103, Germany

Address all correspondence and requests for reprints to: Dr. Edgar Lobos, Institute of Anatomy, University of Leipzig, Liebigstrasse 13, 04103 Leipzig, Germany. E-mail: Edgar.Lobos{at}medizin.uni-leipzig.de.

The mechanisms that promote the transient degenerative changes in the uterus innervation during pregnancy remain incompletely understood. Signaling by the nerve growth factor (NGF)-ß is important for maintaining the density of peripheral sympathetic innervation. Here, we analyzed the spatial and temporal expression of NGF isoforms in the rat uterus using RT-PCR, immunoblot analysis, and immunohistochemistry during pregnancy (d 7, 14, and 21), and postpartum (d 1, 8, and 22). Western blot analysis using antibodies to mature NGF-ß and to proNGF domain demonstrated a significant decrease in mature NGF-ß at gestational d 14 and 21 (term pregnancy) and 1 d postpartum, which paralleled a remarkable accumulation of the 26–28-, 32-, and 60-kDa proNGF forms. There were diminished ratios of mature NGF-ß to proNGF independent of uterus growth on the same gestational days. Immunohistochemistry revealed a progressive NGF-ß decline throughout pregnancy in the myometrium and a near absence at term pregnancy, which contrasted with increased NGF immunostaining in the intermyometrial connective tissue layers. More importantly, proNGF-specific antibodies identified the increased NGF immunoreactivity in the intermyometrial layers at term pregnancy as proNGF and not mature NGF-ß. Alterations in the processing of NGF and accumulation of proNGF in the intermyometrial layers, where axonal degeneration occurs, may contribute significantly to the pregnancy-related uterine denervation and to the control of myometrial activity.