Restoration of Spermatogenesis By Sustained Delivery of Supraphysiological Levels of Testosterone Acetate in Azoospermic Induced Rats

Presentation Number: THR-126
Date of Presentation: March 5th, 2015

Hamed A Benghuzzi*1 and Michelle Tucci2
1Univ of MS Med Ctr, Jackson, MS, 2Univ of Mississippi Med Ctr, Jackson, MS


Previous studies conducted in our labs have demonstrated that sustained delivery of exogenous testosterone (3-5ng/ml) markedly suppressed serum LH, FSH and testicular testosterone levels. Consequently, spermatogonial number declined to approximately 72% of control levels while spermatids were completely devoid from seminiferous tubules. The specific aim of this study was to explore the possible restoration of spermatogenesis in previously induced  azoopermic rats through sustained delivery of supraphysiological level of testosterone acetate (TE) loaded hydroxyapatite (HA) ceramic devices.  A total of 36 adult Sprague Dawley rats were randomly divided into three (Control, Sham and Experimental) equal groups (BW 280-300 gm). Animals in the experimental group initially received TE (40 mg/SC) loaded HA ceramic implants for 12 weeks to induce azoospermia, followed by 8 weeks of exogenous sustained delivery of TE using HA implants loaded with 90 mg TE (15-22 ng/ml; SC).  At the end of 8 weeks of second phase, the animals from each group were sacrificed and the testes were collected by following approved laboratory techniques. The tissues were fixed, processed, embedded, sectioned and stained (H&E) for histopathological evaluation. Germ cell numbers were evaluated using stereological methods and expressed as germ cell number per testis. The results of the study revealed that following the initial TE treatment, serum LH and FSH levels were reduced to 65% and 53% compared to sham operated and intact animals.  At the end of 8 week of second phase, exogenous sustained delivery of TE, resulted in restoring testicular weights to 62-79% of controls while serum LH and FSH levels were remained reduced to 60% and 46% respectively; compared to sham operated and intact animals. On the other hand, as expected, sustained delivery of supraphysiological level of TE was capable of restoring spermatogonial number by 78% at the end of 8 week phase compared to control group. Furthermore, increased number of round and elongated spermatids (p < 0.05) was evident in TE treated animals. We conclude that:  (a) sustained delivery of TE by means of HA delivery devices is a dose dependent (i.e. low dose of TE induced azoospermia and suprphysiological level maintained spermatogenesis), and (ii) TE loaded HA delivery system can be utilized to regulate fertility in males.  


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