Reduced expression of androgen receptor and myosin heavy chain mRNA in cremaster muscle of boys with nonsyndromic cryptorchidism.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Surgery/Urology and Nemours Biomedical Research, AI duPont Hospital for Children, Wilmington, Delaware 19803, USA. jbarthol@nemours.org
Julia Spencer
JS
Barthold
Yanping
Y
Wang
Anita
A
Reilly
Alan
A
Robbins
T Ernesto
TE
Figueroa
Ahmad
A
Banihani
Jennifer
J
Hagerty
Robert E
RE
Akins
D002675:Child, Preschool; D003456:Cryptorchidism / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000235:genetics*; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis*; D011944:Receptors, Androgen / Q000235:genetics*; D013737:Testis
D012333:RNA, Messenger; D011944:Receptors, Androgen; D018995:Myosin Heavy Chains