Protective effects of tadalafil against cisplatin-induced spermatogenic dysfunction.

BACKGROUND: Cisplatin (CDDP) is an effective anticancer drug for the treatment of malignant tumors, such as lung cancer, bladder cancer, and testicular cancer. However, oligozoospermia and azoospermia after administration of CDDP are clinical problems. One of the testicular toxicities of CDDP is known to cause oxidative stress. Tadalafil has been reported to exhibit antioxidant effects and is widely used in clinical practice to treat benign prostatic hyperplasia and erectile dysfunction. Rho-kinase α (ROCK2) regulates cell migration and apoptosis and has been reported to be involved in CDDP-induced nephrotoxicity. The excessive expression of ROCK2 is known to cause oxidative stress. OBJECTIVE: The objective of the current study was to test the effect of tadalafil on the testicular toxicity of CDDP. MATERIAL AND METHODS: Thirty-two rats were used and divided into the following four groups. (1) The control group (CONT), treated with saline on day 1 and saline and dimethyl sulfoxide (DMSO) on days 1-10 intraperitoneally (i.p.) (2) The Tadalafil Group (TAD), treated with saline on day 1, and 0.4 mg/kg tadalafil on days 1-10 i.p. (3) The CDDP group (CD), treated with 7 mg/kg CDDP, saline, and DMSO on days 1-10 i.p. and (4) The CDDP + TAD group (CDT) was treated with 7 mg/kg CDDP on day 1, and 0.4 mg/kg tadalafil on days 1-10 i.p. Testes and epididymides samples were collected on day 11. Biochemical and pathological analyses and quantitative polymerase chain reaction were performed on the excised specimens. RESULTS: CDDP treatment resulted in testicular atrophy, decreased sperm concentration, and atrophy of seminiferous tubules as observed from the testicular histology. Increased apoptosis of seminiferous tubules, oxidative stress, and ROCK2 mRNA expression were observed after CDDP treatment. Treatment with tadalafil improved these adverse effects. CONCLUSION: Tadalafil is a potential drug for reducing CDDP-induced spermatogenic dysfunction. The antioxidant effect of tadalafil may be partly responsible for this phenomenon. ROCK2 and oxidative stress markers may be involved in the possible antioxidant effects of tadalafil. Tadalafil may be considered as one of a treatment option for reducing spermatogenic dysfunction after administration of CDDP.

Improvement in semen parameters by switching steroids in a male congenital adrenal hyperplasia patient with severe oligozoospermia.

Congenital adrenal hyperplasia (CAH) causes hypogonadotropic hypogonadism due to the excessive production of adrenal androgens, which results in hypospermatogenesis in some male patients. We herein present a CAH case with hypogonadotropic hypogonadism and male infertility. A 26-year-old male receiving steroid therapy for 21 hydroxylase deficiency was diagnosed with low gonadotropin levels, an elevated ACTH level, and severe oligozoospermia. The switching from hydrocortisone to dexamethasone resulted in the normalization of gonadotropin levels and semen findings. The couple underwent ICSI-ET, resulting in a live birth. In cases of CAH with hypospermatogenesis, the continuous suppression of ACTH by dexamethasone may restore spermatogenesis.

Differentiation of Human Induced Pluripotent Stem Cells Into Testosterone-Producing Leydig-like Cells.

Late-onset hypogonadism (LOH) syndrome, due to a partial lack of testosterone, decreases the quality of life of older men. Testosterone is mainly secreted by Leydig cells in the testes. Leydig cell transplantation is expected to be a promising alternative to conventional testosterone replacement therapy for LOH syndrome. We herein report a simple and robust protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into Leydig-like cells by doxycycline-inducible overexpression of NR5A1 and treatment with a combination of 8-bromoadenosine-3',5'-cyclic monophosphate (8-Br-cAMP) and forskolin. The differentiated cells expressed the steroidogenic enzyme genes STAR, CYP11A1, CYP17A1, and HSD3B2 and the specific markers of adult Leydig cells HSD17B3, INSL3, and LHCGR. Furthermore, we confirmed the secretion of functional testosterone from the cells into the culture supernatant by a testosterone-sensitive cell proliferation assay. These findings showed that the hiPSCs were able to be differentiated into Leydig-like cells, supporting the expectation that hiPSC-derived Leydig-like cells can be novel tools for treating LOH syndrome.

Optically controlled release of DNA based on nonradiative relaxation process of quenchers.

Optically controlled release of a DNA strand based on a nonradiative relaxation process of black hole quenchers (BHQs), which are a sort of dark quenchers, is presented. BHQs act as efficient energy sources because they relax completely via a nonradiative process, i.e., without fluorescent emission-based energy losses. A DNA strand is modified with BHQs and the release of its complementary strand is controlled by excitation of the BHQs. Experimental results showed that up to 50% of the target strands were released, and these strands were capable of inducing subsequent reactions. The controlled release was localized on a substrate within an area of no more than 5 micrometers in diameter.