Cryptorchidism in LhrKO animals and the effect of testosterone-replacement therapy.
BACKGROUND
The objective of the current study was to characterize the morphological and genetic basis of cryptorchidism.


RESULTS
We investigated cryptorchidism in LH receptor (Lhr) knockout (LhrKO) mice and how testosterone-replacement therapy (TRT) worked to correct the phenotype. The results revealed that while gubernacular development was indistinguishable between Lhr-null and wild-type animals until 7 days of age, it was subsequently severely impaired in null animals. This was due to a reduction in mesenchymal cell division, differentiation into cremaster muscle cells and their delayed maturation. While transcript levels of Hoxa10, Hoxa11, Desrt and Dll1 were indistinguishable, the levels of Notch1, Numb and Lgr8 in the gubernaculum and Insl3 in the testes were lower in Lhr-null than in wild-type siblings. The TRT, which completed testicular descent into the scrotum, corrected the morphological changes and the expression of Lgr8, Numb and Notch, but not Insl3, to wild-type levels. Transection of the genitofemoral nerve did not prevent the TRT effect.


CONCLUSIONS
In summary, cryptorchidism in Lhr-null animals was caused by defects in the gubernacular development due to testosterone deficiency. TRT reversed all the morphological and gene expression changes except Insl3, suggesting that testosterone, not INSL3, secreted by Leydig cells, facilitates the completion of testicular descent.
Yuan
F P
FP
Division of Research, Department of Obstetrics, Gynecology & Women's Health, University of Louisville, Health Sciences Center, Louisville, KY 40292, USA.
Lin
D X
DX
Rao
C V
CV
Lei
Z M
ZM
D000818:Animals; D015415:Biomarkers; D049109:Cell Proliferation; D003456:Cryptorchidism / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D020249:Hormone Replacement Therapy; D007328:Insulin / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009132:Muscles / Q000378:metabolism / Q000473:pathology; D009218:Myosins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010641:Phenotype; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011506:Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051881:Receptor, Notch1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics*; D013737:Testis / Q000254:growth & development / Q000473:pathology / Q000601:surgery; D013739:Testosterone / Q000627:therapeutic use*; D000090324:Tumor Protein, Translationally-Controlled 1
D015415:Biomarkers; D007328:Insulin; C084797:Leydig insulin-like protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C497762:Notch1 protein, mouse; C106293:Numb protein, mouse; D018809:Proliferating Cell Nuclear Antigen; D011506:Proteins; D012333:RNA, Messenger; D051881:Receptor, Notch1; D043562:Receptors, G-Protein-Coupled; D011974:Receptors, LH; C000715648:Tpt1 protein, mouse; D000090324:Tumor Protein, Translationally-Controlled 1; D013739:Testosterone; D009218:Myosins