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Transient Testicular Warming Enhances the Suppressive Effect of Testosterone on Spermatogenesis in Adult Cynomolgus Monkeys (Macaca fascicularis)

Division of Endocrinology (Y.L., C.W., A.P.S.H., C.-M.N., A.L., R.S.S.), Department of Medicine, Harbor-University of California, Los Angeles Medical Center and Los Angeles Biomedical Research Institute at Harbor-University of California, Los Angeles Medical Center, Torrance, California 90502; and State Key Laboratory of Reproductive Biology (Y.-X.L., X.-S.Z., Z.-Y.H., Y.-C.L.), Institute of Zoology, Chinese Academy of Sciences, Beijing 100080, China

Address all correspondence and requests for reprints to: Ronald S. Swerdloff, M.D., Division of Endocrinology and Metabolism, Harbor-University of California, Los Angeles Medical Center, Box 446, 1000 West Carson Street, Torrance, California 90509. E-mail: swerdloff{at}labiomed.org.

Context: The context of the study was to examine whether combined testosterone (T) and heat (H) treatment have additive or synergistic effects on suppression of spermatogenesis.

Objective: The objective of the study was to determine whether T+H induces a greater suppression of spermatogenesis than either treatment alone in monkeys.

Design: The study was a randomized, placebo-controlled study.

Setting: The study was conducted at a primate center in China.

Participants: The study population was comprised of 32 adult cynomolgus monkeys.

Interventions: Groups of eight adult monkeys were treated for 12 wk with: 1) two empty implants (C); 2) two T implants (T); 3) daily testicular heat exposure (43 C for 30 min) for 2 consecutive days (H); or 4) two T implants plus testicular heat exposure (T+H). Treatment was followed by an 8-wk recovery period.

Main Outcome Measures: Measures included sperm counts and germ cell apoptosis.

Results: Serum T levels were elevated in both the T and T+H groups during treatment but not in the C or H group. Sperm counts were transiently suppressed after heat to 16.4% of baseline at 4 wk and then returned to pretreatment levels. Sperm counts were suppressed slowly after T treatment to nadir of 6.4% of pretreatment levels at 12 wk. T+H rapidly suppressed sperm output as early as 4 wk to 3.9% of pretreatment levels that was maintained throughout treatment. The decreased sperm counts were due to increased germ cell apoptosis in all treatment groups. Sperm counts recovered to the pretreatment levels in all groups by 8 wk after treatment.

Conclusion: This proof-of-concept study demonstrates that transient testicular warming enhances and hastens the effect of T implant on the suppression of spermatogenesis in monkeys.

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