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AE Archibong1 *, S Mukherjee2 , D Roa3 , P Kopsombut3 , SK Das2 , EA Turner3
Dept of OB/GYN, Meharry Medical College, Nashville, Tennessee 1
Dept Biochemistry, Meharry Medical College, Nashville, Tennessee 2
The Comprehensive Sickle Cell Center, Meharry Medical College, Nashville, Tennessee 3
We reported in 1996 that testicular function was reduced in male mice treated with hydroxyurea (HU). This study evaluates the fertility of male mice post-HU treatment. Adult ICR mice were randomly assigned to a HU and a control group. Treatment consisted of intraperitoneal injections of 100 mg/kg body weight of HU, five times a week for four weeks. Control animals were similarly injected with vehicle. Five treated and control animals were sacrificed immediately following cessation of HU (time 0). Similar number of post HU-treated and control animals were sacrificed at 1,2,3, and 4 months post-HU to assess indices of fertility. Testes were removed and weighed and cauda epididymal sperm recovered for the assessment of sperm motility and density. Blood samples were also collected from animals via ocular vein punctures and plasma isolated and assayed for testosterone, LH and FSH. Testis weight, stored sperm, sperm motility increased gradually over 4 months post cessation of HU treatment but significantly lower than those of controls. HU caused a reduction in plasma testosterone (0.5±0.01) and LH (0.23±0.04) but resulted in increased plasma FSH (9.54±1.16) compared with controls (time 0 testosterone 6.39±0.5; LH, 1.63±0.08; FSH, 3.60±0.68 ng/ml). However, plasma LH significantly increased over the four months post cessation of HU compared with the value at time 0 (0.62±0.14, 0.56±0.5, 0.63±0.08, 0.62±0.06 ng/ml, for 1 to 4 months after HU, respectively) but lower than control (P<0.05). FSH decreased during this time period (2.46±0.19, 2,81±0.22, 2.08±0.32, 2.08±0.43 ng/ml) but remained significantly lower than that in plasm from control animals. Mating results indicated that litter size was lower among females bred to HU exposed males (5.88±0.83) compared with controls (9.38±0.26). These data suggest that (a) HU perturbs male reproductive efficiency by modulating the levels of the pituitary gonadotropins and (b) its effects on reproduction can be protracted even after the cessation of treatments. This project was supported by RCMI Grant #521587.
This abstract is being presented on Monday, August 2 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.