Nitric oxide a mediator of FSH effect on testicular blood flow

Introduction: Gonadotrophin (Gn) treatment is able to increase intratesticular blood flow (IBF) and therefore improve sperm fertilization potential. A nitric oxide (NO) mediated mechanism may play a role. Presence of NO synthase (NOS) was demonstrated in epididymal epithelial cells, seminiferous tubules and vas deferens, as well as in the endothelial cells and nerve plexuses within the adventitia of blood vessels supplying reproductive tissues. This study aimed to evaluate whether the increase in IBF supply in response to long term Gn treatment is accompanied by an increase in NO seminal plasma levels in normogonadotropic males with severe oligoasthenoteratozoospermia (OTA). Main Outcome measures: Fiftheen normogonadotropic males affected by severe OTA received 150 IU of FSH (Menogon, Ferring, Milan, Italy) three times a week for three months. Before starting treatment and at month 3 of therapy the following examinations were performed: seminal plasma levels of nitrite/nitrate, ultrasound scanning of testicular volume, Doppler evaluation of intratesticular vascular resistance, serum hormones levels, conventional semen evaluation. Statistical analysis was performed by Wilcoxon test; limit of statistical significance was p<0,05. Results: Seminal plasma concentration of nitrite/nitrate did not result significantly higher than baseline values after 3 months of therapy (p= 0,09). The resistance index of both intratesticular arteries significantly decreased after three months of treatment (p=0,02 p= 0,007 for right and left testis respectively) At month 3 FSH serum levels increased significantly (p=0,03) while LH, testosterone, estradiol and testicular volume did not change. Conventional semen parameters revealed a significant increase in sperm number (p=0.003) Conclusions: Gn treatment increases IBF but not NO seminal plasma levels suggesting that NOS of epididymal epithelial cells, seminiferous tubules and vas deferens is not influenced by FSH stimulation. The improvement in sperm quality observed after FSH treatment can not be explained by the increase in NO seminal plasma levels but can be related to the increase in IBF. Infact the enhance of oxigen supply may reduce the exposure of germ cells to reactive oxigen species which are associated with generation of DNA breakage and lipid peroxidation. Further investigations are needed to completely define the role of NOS system in the physiopatology of the genital tract.