Developmental Mechanisms of Undescended Testis
Target Investigator:
Julia Spencer Barthold, MD
Principal Research Scientist

Collaborators: Marcella Devoto, Ph.D., Children’s Hospital of Pennsylvania
Kamin Johnson, Ph.D., Nemours Biomedical Research
Mentors: Ayyappan Rajasekaran, Ph.D., Nemours Biomedical Research
N. Carolyn Schanen, M.D., Ph.D., Nemours Biomedical Research


We are studying a model of inherited cryptorchidism, the orl rat, in order to better understand the genetic and environmental factors that contribute to risk for this very common disease. The phenotype of this strain is similar to the most common form of the human disease. Our data suggest that cryptorchidism in the orl model is associated with allelic variation at 2 or more genomic loci and may affect androgen receptor signaling and muscle development in the fetal gubernaculum.

In addition, we have shown that the fetal orl rat testis is more susceptible to the toxicity of di-n-butyl phthalate (DBP) as measured by endpoints such as inhibition of steroidogenic gene expression and frequency of multinucleated gonocytes. In complementary studies, we have analyzed clinical samples to identify possible genetic variants within 2 major candidate gene groups, HOX and estrogen receptor, for association with cryptorchidism. Our future experimental work will focus on identifying novel gene candidates in the human population, informed by our genomic and molecular studies of the orl rat.


Deconvolution microscopy gubernacula from gesta tional day 20 fetuses. Wt (left) and orl (right) gubernaculum stained for myogenin (green) and troponin T (red); bars, 150 microns.

Related Publications:

    Barthold J.S., Si X., Stabley D., Sol-Church K., McCahan S.M. Failure of shortening and inversion of the perinatal gubernaculum in the cryptorchid LE/orl rat. J Urol. 176:1612-1617, 2006.
    Wang Y., Barthold J., Kanetsky P.A., Casalunovo T., Pearson E., Manson J. Allelic variants in HOX genes in cryptorchidism. Birth Defects Res A Clin Mol Teratol. 79:269-75, 2007.
    Barthold J.S., McCahan S.M., Singh A.V., Knudsen T.B., Si X., Campion L. and Akins R.E. Altered expression of muscle- and cytoskeleton-related genes in a rat strain with inherited cryptorchidism. J Androl. 29:352-366. Epub Jan 24 2008.
    Wang Y., Barthold J., Figueroa E., González R., Noh P.H., Wang M. and Manson J. Analysis of five single nucleotide polymorphisms in the ESR1 gene in cryptorchidism. Birth Defects Res A Clin Mol Teratol, May 1, 2008. Epub ahead of print.