Beneficial effects of pentoxifylline on spermatogenesis and germ cell apoptosis in stallions subjected to scrotal heat stress

Abstract

This study evaluated the effects of oral pentoxifylline on testicular biometry, histology, and gene expression in stallions subjected to scrotal heat stress. Fourteen stallions were divided into three groups: Control (CRL, n = 4), Testicular Degeneration (DEG, n = 5), and Testicular Degeneration Treated with Pentoxifylline (DEG + PTX, n = 5). Testicular degeneration was induced by scrotal insulation, twice daily, over two consecutive days (D-1 and D0). Starting the next day (D1), oral pentoxifylline (17 mg/kg) was administered every 12 h for 30 days. Testicular biometry was measured using a caliper from D-5 to D60. On days 30 and 60, testicular biopsies were collected for histopathology and gene expression analysis of BAX, CASP8, CASP9, FAS, HSF1, and PTGS2 using RT-qPCR. Pentoxifylline reduced histological damage, with the DEG + PTX group showing less pronounced basal lamina undulation and seminiferous tubule atrophy compared to the DEG group. However, it did not fully prevent lesions like germ cell vacuolization, which was reflected macroscopically by a reduction in testicular volume in both degenerated groups. The protective effects of pentoxifylline on testicular tissue can be attributed to its ability to reduce BAX expression, prevent CASP8 and CASP9 activation, and promote cellular protective mechanisms through HSF1 activation at D30. These results highlight pentoxifylline's potential as a therapeutic agent for equine testicular damage due to scrotal heat stress, suggesting the need for further research on optimal dosage and treatment duration.