User:Quinnjkq/sandbox

Ideas:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3566290/

To date, there are 20 published reports of familial testicular torsion, which has raised the possibility of a genetic basis for the disease.[3, 13–22] A prospective series of 70 boys with torsion identified familial testicular torsion in 11.4% and one case with a three generational family.[3] Although previously there had been no candidate genes for human testicular torsion, recently the INSL3 hormone and its receptor, RXLF2, have been investigated as candidate genes. The impetus for this was the observation that Insl3knockout mice, which uniformly manifest intraabdominal bilateral cryptorchidism with accompanying heat-induced testicular atrophy in adulthood, additionally have spontaneous testicular torsion. The risk for active torsion was greatest in the ‘adolescent’ mice and loss of the testis (not just testicular atrophy) was observed the most in the older adult mice. Thus, the altered anatomy predisposed the mice to the torsion event, which was witnessed most commonly peripubertally. [23, 24] When comparing this mouse model to the human condition, similarities include that torsion is primarily a peripubertal event while differences include that human testicular torsion occurs in the scrotum and not intraabdominally, as in the mice. It is well established that in humans and mice, INSL3 is produced by testicular Leydig cells. By studying the Insl3 mutant mice, it has become clear that INSL3 acts early on the embryonic gubernaculum to masculinize and enlarge it.[23] This allows for the later action, mediated by testosterone, which may induce transinguinal testicular descent with gubernacular regression and potentially scrotal fixation. This particular function makes this hormone-receptor signaling cascade a strong candidate for having at least a partial role in the etiology of human torsion, as it has been associated in human cryptorchidism.

With this in mind, our group tested genomic DNA samples from 39 males (11 neonatal: 21 pre- or peri-pubertal; 7 pubertal) with surgically confirmed testicular torsion for mutations in INSL3 and RXFP2 [25]. Bilateral testicular torsion was present in 2/11 (18%) neonatal and 2/28 (7%) older cases. A positive family history of torsion was noted in 29% of neonatal and 33% of older cases. We did not detect any functionally significant mutations in INSL3 or RXFP2, leading one to conclude that mutations in these genes are not a common de novo or inherited cause for testicular torsion. However, this ligand-receptor signaling system may still be important in human testicular torsion at other yet to be determined levels of regulation.