Reduced Expression of Androgen Receptor and Myosin Heavy Chain mRNA in Cremaster Muscle of Boys with Nonsyndromic Cryptorchidism

Surgery/Urology and Nemours Biomedical Research, AI duPont Hospital for Children, Wilmington, Delaware.
The Journal of urology (Impact Factor: 4.47). 08/2012; 188(4 Suppl):1411-6. DOI: 10.1016/j.juro.2012.06.033
Source: PubMed


To better define the developmental mechanisms of nonsyndromic cryptorchidism, we measured the expression of hormone receptor and muscle type specific mRNAs in target tissues of boys with and those without nonsyndromic cryptorchidism.
Prospectively collected cremaster muscle and/or hernia sac tissues from boys with congenital (79) or acquired (66) nonsyndromic cryptorchidism and hernia/hydrocele (controls, 84) were analyzed for hormone receptor (RXFP2, AR, ESR1, ESR2) and myosin heavy chain specific (MYH1, MYH2, MYH7) mRNA expression using real-time reverse transcriptase polymerase chain reaction. Log transformed mRNA, phenotype and feeding history data were statistically analyzed using Pearson's correlation, ANOVA and 2-sample t tests.
AR mRNA expression was higher in cremaster muscle than in sac tissue, and significantly lower in congenital and acquired nonsyndromic cryptorchidism cases vs controls (p <0.01). Type 1 (slow/cardiac) MYH7 mRNA expression was also significantly reduced in both nonsyndromic cryptorchidism groups (p ≤0.002), while a reduction in type 2 (fast) MYH2 expression was more modest and significant only for the congenital cryptorchidism group (p <0.05). Cremasteric MYH7 and AR levels were strongly correlated (r(2) = 0.751, p <0.001). MYH7 and ESR1 mRNA levels were higher and lower, respectively, in boys with nonsyndromic cryptorchidism who were fed soy formula. Expression of other genes was not measurable.
Our data suggest that boys with congenital and acquired nonsyndromic cryptorchidism differentially express AR and slow twitch specific MYH7 mRNA in the cremaster muscle, and that MYH7 expression is correlated with AR levels and soy formula use. These differences in gene expression may reflect aberrant hormonal signaling and/or innervation during development with the potential for secondary functional effects and failed testicular descent.

Download full-text


Available from: Alan Robbins, Apr 25, 2014
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Androgens and insulin-like 3 (INSL3) are required for development of the fetal gubernaculum and testicular descent. Prior studies suggested that the INSL3-exposed fetal gubernacular transcriptome is enriched for genes involved in neural pathways. In the present studies, we profiled the transcriptome of fetal gubernaculum explants exposed to dihydrotestosterone (DHT) and compare this response with that of INSL3. We exposed fetal (E17) rat gubernacula to DHT for 24 h (10 and 30 nM) or 6 h (1 and 10 nM) in organ culture and analyzed gene expression relative to vehicle-treated controls using Affymetrix arrays. Results were annotated using functional, pathway and promoter analyses and independently validated for selected transcripts using qRT-PCR. Transcripts were differentially expressed after 24 but not 6 h. Most highly overrepresented functional categories included those related to gene expression, skeletal and muscular development and function, and WNT signaling. Promoter response elements enriched in the DHT-specific transcriptome included consensus sequences for c-ETS1, ELK1, CREB, CRE-BP1/c-Jun, NRF2 and USF. We observed that 55% of DHT probesets were also differentially expressed after INSL3 exposure and the direction of change was the same in 96%. qRT-PCR confirmed that DHT increased expression of the INSL3-responsive genes Crlf1 and Chrdl2 but reduced expression of Wnt4. We also validated reduced expression of Tgfb2 and Cxcl12 and increased Slit3 expression following DHT exposure. These data suggest a robust overlap in the DHT- and INSL3-regulated transcriptome that may be mediated in part by CREB signaling and a common WNT pathway response for both hormones in the fetal gubernaculum.
    Full-text · Article · Oct 2013 · Biology of Reproduction
  • [Show abstract] [Hide abstract]
    ABSTRACT: Spermatogenesis is a fundamental process in sexual development and reproduction, in which the diploid spermatogonia transform into haploid mature spermatozoa. This process is under the regulation of multiple factors and pathway. Myosin has been implicated in various aspects during spermatogenesis. Myosins constitute a diverse superfamily of actin-based molecular motors that translocate along microfilament in an ATP-dependent manner, and six kinds of myosins have been proved that function during spermatogenesis. In mitosis and meiosis, myosins play an important role in spindle assembly and positioning, karyokinesis and cytokinesis. During spermiogenesis, myosins participate in acrosomal formation, nuclear morphogenesis, mitochondrial translocation and spermatid individualization. In this review, we summarize current understanding of the functions of myosin in spermatogenesis and some reproductive system diseases such as testicular tumors and prostate cancer, and discuss the roles of possible upstream molecules which regulate myosin in these processes.
    No preview · Article · Oct 2015 · Gene