TY - JOUR
T1 - Changes in Gene Expression and Metabolism in the Testes of the Rat following Spinal Cord Injury
AU - Fortune, Ryan D.
AU - Grill, Raymond J.
AU - Beeton, Christine
AU - Tanner, Mark
AU - Huq, Redwan
AU - Loose, David S.
N1 - Funding Information:
Acknowledgments We are grateful for the U.S. Department of Defense's generous funding and support (Award Number: W81XWH-12-1-0481). Thanks to Feng Li, PhD, the Metabolomics core, Advance Technology Cores of Baylor College of Medicine, for his proficient analysis of bile acids in the serum. We would also like to thank Darren Boehning, PhD, UTHealth, for his generosity in teaching and helping perform caspase assays on our samples; and Redwan Huq, Baylor College of Medicine, for his proficiency in flow cytometry, as well as his willingness to troubleshoot and dedication to proper science. We thank Ashley Hood and the rest of the Center for Clinical and Translational Sciences TL1 program for generous funding and support. We would like to thank Jeff Frost, PhD, UTHealth, for helping to teach proper lab techniques. Thanks to Rebecca Berdeaux, PhD, UTHealth, for generous use of lab equipment. Finally, thanks to Sarah Riosa and Alissa Poteete, MS, for their patience, support, and technical assistance.
Publisher Copyright:
© Copyright 2017, Mary Ann Liebert, Inc. 2017.
PY - 2017/3/15
Y1 - 2017/3/15
N2 - Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males also will frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 h) and chronically up to 1.5 years post-injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate. Using messenger RNA and metabolomic assessments, we describe molecular and cellular changes that occur within the testis of adult rats over an acute to chronic time period. From 24 h, 72 h, 28 days, and 90 days post-SCI, the testis reveal a distinct time course of pathological events. The testis show an acute drop in normal sexual organ processes, including testosterone production, and establishment of a pro-inflammatory environment. This is followed by a subacute initiation of an innate immune response and loss of cell cycle regulation, possibly due to apoptosis within the seminiferous tubules. At 1.5 years post-SCI, there is a chronic low level immune response as evidenced by an elevation in T cells. These data suggest that SCI elicits a wide range of pathological processes within the testes, the actions of which are not restricted to the acute phase of injury but rather extend chronically, potentially through the lifetime of the subject. The multiplicity of these pathological events suggest a single therapeutic intervention is unlikely to be successful.
AB - Spinal cord injury (SCI) results in devastating changes to almost all aspects of a patient's life. In addition to a permanent loss of sensory and motor function, males also will frequently exhibit a profound loss of fertility through poorly understood mechanisms. We demonstrate that SCI causes measureable pathology in the testis both acutely (24 h) and chronically up to 1.5 years post-injury, leading to loss in sperm motility and viability. SCI has been shown in humans and rats to induce leukocytospermia, with the presence of inflammatory cytokines, anti-sperm antibodies, and reactive oxygen species found within the ejaculate. Using messenger RNA and metabolomic assessments, we describe molecular and cellular changes that occur within the testis of adult rats over an acute to chronic time period. From 24 h, 72 h, 28 days, and 90 days post-SCI, the testis reveal a distinct time course of pathological events. The testis show an acute drop in normal sexual organ processes, including testosterone production, and establishment of a pro-inflammatory environment. This is followed by a subacute initiation of an innate immune response and loss of cell cycle regulation, possibly due to apoptosis within the seminiferous tubules. At 1.5 years post-SCI, there is a chronic low level immune response as evidenced by an elevation in T cells. These data suggest that SCI elicits a wide range of pathological processes within the testes, the actions of which are not restricted to the acute phase of injury but rather extend chronically, potentially through the lifetime of the subject. The multiplicity of these pathological events suggest a single therapeutic intervention is unlikely to be successful.
KW - blood-testes barrier
KW - gene expression
KW - metabolomics
KW - microarray
KW - spinal cord injury
UR - http://www.scopus.com/inward/record.url?scp=85015230664&partnerID=8YFLogxK
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U2 - 10.1089/neu.2016.4641
DO - 10.1089/neu.2016.4641
M3 - Article
C2 - 27750479
AN - SCOPUS:85015230664
SN - 0897-7151
VL - 34
SP - 1175
EP - 1186
JO - Journal of Neurotrauma
JF - Journal of Neurotrauma
IS - 6
ER -