PMID- 18222913 OWN - NLM STAT- MEDLINE DCOM- 20081020 LR - 20220309 IS - 1939-4640 (Electronic) IS - 0196-3635 (Linking) VI - 29 IP - 3 DP - 2008 May-Jun TI - Altered expression of muscle- and cytoskeleton-related genes in a rat strain with inherited cryptorchidism. PG - 352-66 LID - 10.2164/jandrol.107.003970 [doi] AB - Development of the fetal gubernaculum is a prerequisite for testicular descent and dependent on insulin-like 3 and androgen, but knowledge of downstream effectors is limited. We analyzed transcript profiles in gubernaculum and testis to address changes occurring during normal and abnormal testicular descent in Long Evans wild-type (wt) and cryptorchid (orl) fetuses. Total RNA from male wt and orl gubernacula (gestational days [GD]18-20), wt female gubernacula (GD18), and testis (GD17 and 19) was hybridized to Affymetrix GeneChips. Statistical analysis of temporal, gender, and strain-specific differences in gene expression was performed with the use of linear models analysis with empirical Bayes statistics and analysis of variance (gubernaculum) and linear analysis (testis). Overrepresented common gene ontology functional categories and pathways were identified in groups of differentially expressed genes with the Database for Annotation, Visualization, and Integrated Discovery. Transcript profiles were dynamic in wt males between GD18-19 and GD20, comparatively static in orl GD18-20 gubernaculum, and similar in wt and orl testis. Functional analysis of differentially expressed genes in wt and orl gubernaculum identified categories related to metabolism, cellular biogenesis, small GTPase-mediated signal transduction, cytoskeleton, muscle development, and insulin signaling. Genes involved in androgen receptor signaling, regulated by androgens, or both were overrepresented in differentially expressed gubernaculum and testis gene groups. Quantitative reverse transcription polymerase chain reaction (RT-PCR) confirmed differential expression of genes related to muscle development, including Myog, Tnnt2, Fst, Igf1, Igfbp5, Id2, and Msx1. These data suggest that the orl mutation results in a primary gubernacular defect that affects muscle development and cytoskeletal function and might alter androgen-regulated pathways. FAU - Barthold, Julia S AU - Barthold JS AD - Nemours Biomedical Research and Division of Urology, A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA. jbarthol@nemours.org FAU - McCahan, Suzanne M AU - McCahan SM FAU - Singh, Amar V AU - Singh AV FAU - Knudsen, Thomas B AU - Knudsen TB FAU - Si, Xiaoli AU - Si X FAU - Campion, Liam AU - Campion L FAU - Akins, Robert E AU - Akins RE LA - eng GR - P20 RR020173/RR/NCRR NIH HHS/United States GR - P20 RR-020173-01/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20080124 PL - United States TA - J Androl JT - Journal of andrology JID - 8106453 RN - EC 3.6.5.2 (Monomeric GTP-Binding Proteins) SB - IM MH - Animals MH - Cryptorchidism/*genetics/metabolism MH - Cytoskeleton/*genetics/metabolism MH - Energy Metabolism/genetics MH - Fetal Development/physiology MH - Gene Expression MH - Gene Expression Profiling MH - Male MH - Monomeric GTP-Binding Proteins/metabolism MH - Muscle Development/*genetics MH - Oligonucleotide Array Sequence Analysis MH - Rats MH - Signal Transduction/physiology MH - Testis/*growth & development/metabolism EDAT- 2008/01/29 09:00 MHDA- 2008/10/22 09:00 CRDT- 2008/01/29 09:00 PHST- 2008/01/29 09:00 [pubmed] PHST- 2008/10/22 09:00 [medline] PHST- 2008/01/29 09:00 [entrez] AID - jandrol.107.003970 [pii] AID - 10.2164/jandrol.107.003970 [doi] PST - ppublish SO - J Androl. 2008 May-Jun;29(3):352-66. doi: 10.2164/jandrol.107.003970. Epub 2008 Jan 24.