Occurrence of testicular microlithiasis in androgen insensitive hypogonadal mice.
BACKGROUND
Testicular microliths are calcifications found within the seminiferous tubules. In humans, testicular microlithiasis (TM) has an unknown etiology but may be significantly associated with testicular germ cell tumors. Factors inducing microlith development may also, therefore, act as susceptibility factors for malignant testicular conditions. Studies to identify the mechanisms of microlith development have been hampered by the lack of suitable animal models for TM.


METHODS
This was an observational study of the testicular phenotype of different mouse models. The mouse models were: cryptorchid mice, mice lacking androgen receptors (ARs) on the Sertoli cells (SCARKO), mice with a ubiquitous loss of androgen ARs (ARKO), hypogonadal (hpg) mice which lack circulating gonadotrophins, and hpg mice crossed with SCARKO (hpg.SCARKO) and ARKO (hpg.ARKO) mice.


RESULTS
Microscopic TM was seen in 94% of hpg.ARKO mice (n=16) and the mean number of microliths per testis was 81+/-54. Occasional small microliths were seen in 36% (n=11) of hpg testes (mean 2+/-0.5 per testis) and 30% (n=10) of hpg.SCARKO testes (mean 8+/-6 per testis). No microliths were seen in cryptorchid, ARKO or SCARKO mice. There was no significant effect of FSH or androgen on TM in hpg.ARKO mice.


CONCLUSIONS
We have identified a mouse model of TM and show that lack of endocrine stimulation is a cause of TM. Importantly, this model will provide a means with which to identify the mechanisms of TM development and the underlying changes in protein and gene expression.
O'Shaughnessy
Peter J
PJ
Institute of Comparative Medicine, Division of Cell Sciences, University of Glasgow Veterinary School, Bearsden Rd, Glasgow G61 1QH, UK. p.j.oshaughnessy@vet.gla.ac.uk
Monteiro
Ana
A
Verhoeven
Guido
G
De Gendt
Karl
K
Abel
Margaret H
MH
D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003456:Cryptorchidism / Q000235:genetics / Q000503:physiopathology; D013196:Dihydrotestosterone / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D006062:Gonadotropins / Q000235:genetics / Q000502:physiology; D006801:Humans; D007006:Hypogonadism / Q000235:genetics / Q000503:physiopathology*; D020347:Lithiasis / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011944:Receptors, Androgen / Q000235:genetics / Q000502:physiology; D012708:Sertoli Cells / Q000378:metabolism; D013733:Testicular Diseases / Q000235:genetics / Q000473:pathology*; D013737:Testis / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology
D000728:Androgens; D006062:Gonadotropins; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D013739:Testosterone