PARENT SESSION
TOXICOLOGY

Monday, August 2, 2004
10:30 AM–12:30 PM
Buchanan Courtyard

(90) HYDROXYUREA TREATMENT OF ADULT MALES (TRANSGENIC MOUSE MODEL) WITH SICKLE CELL DISEASE COMPROMISES TESTICULAR AND EPIDIDYMAL FUNCTION.

Jones, Kea¹, Aguinaga, Maria del Pilar¹, Niaz, Mohammad¹, Williams, Vincent¹, Brooks, Cynthia ¹, Turner, Tiffany¹, Archibong, Anthony, ¹ Meharry Medical College, Nashville, TN

ABSTRACT- This study was designed to evaluate the effect of hydroxyurea (HU) on testis and epididymal function. Adult male transgenic sickle cell mice (strain Tg58xTg98) were randomly assigned to a treatment and a control group. Treatment consisted of 25 mg/kg body weight of HU administered by oral gavage, seven days a week for a maximum of eight weeks. Control mice received the vehicle for HU (saline) as described for the treatment group. Some treated and control animals were anesthetized on day28 or 56 post initiation of treatment, with isoflurane followed by a mid-ventral laparotomy to permit blood collection by renal vein and cardiac puncture. Serum samples were extracted from blood by centrifugation at 1000 x g for 10 minutes prior to being stored at –20°C until used for determining circulatory reproductive hormone concentrations. Subsequently, testes and epididymides were recovered and weighed and cauda epididymides were excised, stored sperm recovered for the assessment of sperm density and motility in Whitten′s medium (Whitten and Biggers, 1968; J Reprod Fertil 17:399). HU decreased testis weight (month 1, 0.09+ 0.004g; month 2, 0.06+ 0.003g; P<0.005) compared with controls (month 1, 0.15+ 0.001g; month 2, 0.16+ 0.01g) that did not differ. HU also decreased circulating testosterone concentrations (P<0.05) as well as sperm density, after the second month of treatment (month 2, 4.00+ 2.32 million) compared with controls (month 2, 13.00+ 2.93 million). Progressive sperm motility was also adversely affected by HU on the second month of treatment (month 2, 2.50+ 0.50%) compared with controls (second month, 45.00+ 4.67%). These data demonstrate that HU has toxic effects on sperm production and testosterone synthesis and release, probably due to inhibition of DNA synthesis and epididymal sperm maturation. This project was supported by HD020419-19S1, 5KO1-HL003141, and 1U54 HD44315-01.

KEY WORDS: Testis, Epididymis, Hydroxyurea, Testosterone