Nitric Oxide Synthase is Necessary for Normal Urogenital Development
|Christopher Bond1, Omer Onur Cakir1, Kevin T McVary2 and Carol A Podlasek1*|
|1Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA|
|2Division of Urology, Southern Illinois University School of Medicine, Springfield, IL, USA|
|*Corresponding Author :||Carol Podlasek
PhD, Department of Urology
303 E. Chicago Avenue, Tarry 16-763
Chicago, IL 60611, USA
E-mail: [email protected]
|Received September 05, 2013; Accepted October 29, 2013; Published November 04, 2013|
|Citation: Bond C, Cakir OO, McVary KT, Podlasek CA (2013) Nitric Oxide Synthase is Necessary for Normal Urogenital Development. Andrology 2:108. doi:10.4172/2167-0250.1000108|
|Copyright: © 2013 Bond C, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.|
Introduction: Neuronal nitric oxide synthase (NOS-I) is significantly decreased with Cavernous Nerve (CN) injury in Erectile Dysfunction (ED) models. Increased apoptosis and collagen deposition accompany decreased NOS/CN injury, however these changes are typically attributed to the altered signaling of other factors, and a contribution of NOS in maintenance of urogenital structures has not previously been examined. Morphological changes in the corpora cavernosa occur at the same time as decreased NOS, suggesting a potential connection between decreased/inhibited NOS and morphological changes associated with ED. In this study we propose that NOS impacts urogenital morphology during development and will examine this hypothesis by NOS inhibition with L-NAME.
Methods: Primary outcomes were H&E, western and TUNEL to determine if penis, prostate and bladder morphology were altered with L-NAME treatment of Postnatal day 4 (P4) Sprague Dawley rats for 8 days. Tissue weight and immunohistochemical analysis for NOS were performed. Secondary evaluation of NOS-I regulation by Sonic Hedgehog (SHH) was examined by SHH inhibition in the Pelvic Ganglia (PG) and NOS-I protein was quantified by western in the PG/CN and penis. Nos abundance was quantified by RT-PCR during urogenital development and after CN injury.
Results: Apoptosis increased and penis, prostate and bladder morphology were altered with L-NAME. NOS inhibition decreased bladder weight 25%. SHH inhibition decreased NOS-I 35% in the PG/CN and 47% in the penis. Nos-III expression spiked within the first two weeks after birth in the penis but remained abundant in the adult. In the prostate, Nos-III was abundant immediately after birth and declined steadily with age. Nos-I expression in the PG/ CN decreased sharply with CN injury and returned to baseline by 7 days.
Conclusions: NOS is required for normal urogenital development. Since NOS is decreased with ED, it may contribute to the abnormal morphology observed in ED patients and animal models.