Altered Sertoli Cell Function Contributes to Spermatogenic Arrest in Dogs with Chronic Asymptomatic Orchitis

Acquired infertility due to chronic asymptomatic orchitis (CAO) is a common finding in male dogs. It is characterized by spermatogenic arrest, a significant reduction in spermatogonia, immune cell infiltration and a disruption of the blood-testis barrier. Sertoli cells are a key factor for spermatogenesis and the testicular micromilieu. We hypothesize altered Sertoli cell function to be involved in the pathogenesis of canine CAO. Consequently, the aim was to gain further insights into the spermatogonial stem cell niche and Sertoli cell function in CAO-affected dogs. Therefore, the testicular expression of the Sertoli cell-derived factors <i>bFGF</i>, <i>GDNF</i>, <i>WNT5A</i>, <i>BMP4</i>, <i>CXCL12</i> and <i>LDHC</i> were evaluated in 15 CAO testis tissues and 10 normospermic controls by relative quantitative real-time PCR (qPCR). Additionally, the protein expression patterns of bFGF, GDNF and WNT5A were visualized immunohistochemically (IHC). This study revealed an overexpression of bFGF (IHC, <i>p</i> < 0.0001), <i>GDNF</i> (qPCR, <i>p</i> = 0.0036), WNT5A (IHC, <i>p</i> = 0.0066) and <i>CXCL12</i> (qPCR, <i>p</i> = 0.0003) and a reduction in <i>BMP4</i> (qPCR, <i>p</i> = 0.0041) and <i>LDHC</i> (qPCR, <i>p</i> = 0.0003) in CAO-affected testis in dogs, clearly confirming impaired Sertoli cell function in canine CAO. Sertoli cell function is essential for spermatogenesis and must be considered for potential therapeutic approaches.