DIFFERENTIAL HISTOPATHOLOGICAL ASSESSMENT OF TESTICULAR FUNCTION UPON LONG-TERM EXPOSURE TO SUSTAINED DELIVERY OF TESTOSTERONE AND DIHYDROTESTOSTERONE.

The specific aim of this study was to assess, histopathologically, the seminiferous tubules area and germ layers upon the exposure to sustained delivery of testosterone (TE) and dihydrotestosterone (DHT) through tricalcium phosphate lysine devices (TCPL). A total of 140 adult Male rats (280-320 gm) were randomly divided into four equal groups. Groups 1 and 2 animals were implanted with TCPL loaded with 40 mg TE and 40 mg DHT, respectively. Groups 3 and 4 animals served as a sham group (empty devices), and a control group. For the treatment and sham groups, serum testosterone, LH and FSH levels were monitored at treatment periodic intervals of 1, 3, 6, 9, and 12 months. Histopathological evaluation of testicular issues (H&E) was conducted for each phase following standardized lab procedures. Results of this study indicated that: (i) endogenous testosterone and gonadotropin (LH/FSH) levels were suppressed to undetectable levels (<0.2 ng/mL) for a 1-year period by the sustained delivery of either TE or DHT compared to control and sham groups, (ii) a decrease in the luminal areas of seminiferous tubules retrieved from DHT treated group (P<0.05) in comparison with TE, (iii) an arrest of germ layers at the secondary spermatocyte at the end of the 3 month treatment with DHT and 1 month exposure to TE, and (iv) spermatogonia were intact and exhibited normal N/C ration for TE or DHT treated animals compared to sham and control groups. The overall conclusion obtained from this study indicated that TE loaded TCPL delivery devices can be used to induce azoospermia at an early phase and also provided evidence of the increased TE effectiveness to regulate fertility in an animal model.