Methoxsalen deteriorative effects on the testicular parenchyma and testosterone synthesis gene expression in male rats

Studies show that psoralens have adverse effects on the reproductive system. This study investigated the impact of methoxsalen in combination with UVA on testicular parenchyma and the expression level of testosterone synthesis pathway genes as well as sperm quality and quantity, in rats. 24 adult male rats were randomly divided into 4 groups: control, sham group receiving the same volume of the corn oil + ultraviolet radiation (UVA): 0.046 J/cm2, for 20 min, and experimental groups receiving 37.5, and 75 mg/kg doses of Methoxalen + UVA, respectively (MTX 37.5 and MTX 75). After 48 days' serum samples were separated to measure the concentrations of LH, FSH, and Testosterone hormones. Spermatozoa were obtained from the epididymis for analysis of quality, quantity, morphology, viability and motility. Additionally, testicular tissue was subjected to stereological analysis to evaluate structural changes, and mRNA expression levels of STAR, Cyp11a1, Hsd17b3, Bcl-2, and Caspase-9 were measured. The results show detrimental effects of MTX in testosterone, sperm parameters, weight, and volume of the testis. Also, the volume of sperm and testosterone-producing cells such as Leydig cells decreased after treatment. The expression level of STAR, Cyp11a1, Hsd17b3, and Bcl-2 mRNAs were diminished, though the mRNA expression of caspase-9 and serum level of LH, and FSH in the high dose of the methoxsalen group increased compared to the sham group. Administering methoxsalen along with UVA can cause more severe damage to testicular parenchyma at high doses and reduce the mRNA expression level of genes involved in the testosterone synthesis pathway. Therefore, administering this drug is not recommended for people who are planning to become pregnant, although more studies are needed in this field.