Adverse Effects of a Clinically Relevant Dose of Hydroxyurea Used for the Treatment of Sickle Cell Disease on Male Fertility Endpoints

作者：Kea M Jones; Mohammad S Niaz; Cynthia M Brooks; Shannon I Roberson; Maria P Aguinaga; Edward R Hills; Valerie Montgomery Rice; Phillip Bourne; Donald Bruce; Anthony E Archibong

来源：International Journal of Environmental Research and Public Health, 2009, 6(3): 1124-1144.

DOI：10.3390/ijerph6031124

• Hydroxyurea
• Hypogonadism
• testicular failure
• transgenic sickle cell mouse
• Sickle cell disease
• spermatozoa
• testosterone

Two experiments were conducted to determine: 1) whether the adult male transgenic sickle cell mouse (Tg58 ℅ Tg98; TSCM), exhibits the patterns of reproductive endpoints (hypogonadism) characteristic of men with sickle cell disease (SCD) and 2) whether hydroxyurea (HU) exacerbates this condition. In Experiment 1, blood samples were collected from adult age-matched TSCM and ICR mice (ICRM) (N = 10/group) for plasma testosterone measurements. Subsequently, mice were sacrificed, testes excised and weighed and stored spermatozoa recovered for the determination of sperm density, progressive motility and percentage of spermatozoa with normal morphology. In experiment 2, adult male TSCM were orally treated with 25 mg HU/kg body weight/day for 28 or 56 days. Control mice received the vehicle for HU (saline) as described above. At the end of the treatment periods, blood samples were collected for quantification of circulating testosterone. Subsequently, mice were sacrificed, testes and epididymides were recovered and weighed and one testis per mouse was subjected to histopathology. Stored spermatozoa were recovered for the determination of indices of sperm quality mentioned in Experiment 1. Testis weight, stored sperm density, progressive motility, percentage of spermatozoa with normal morphology and plasma testosterone concentrations of TSCM were significantly lower by 40, 65, 40, 69 and 66%, respectively than those of ICRM. These data indicate that adult TSCM used in this study suffered from hypogonadism, characteristically observed among adult male SCD patients. In Experiment 2, HU treatment significantly decreased testis weight on day 28, (0.09 ㊣ 0.004g) that was further decreased on day 56 (0.06 ㊣ 0.003g; treatment x time interaction) compared with controls (day 28, 0.15 ㊣ 0.01g; day 56, 2, 0.16 ㊣ 0.01g). Concomitant with a 52% shrinkage (P

• 出版日期2009