scholarly journals Transient Scrotal Hyperthermia and Levonorgestrel Enhance Testosterone-Induced Spermatogenesis Suppression in Men through Increased Germ Cell Apoptosis

2007 ◽  
Vol 92 (8) ◽  
pp. 3292-3304 ◽  
Author(s):  
Christina Wang ◽  
Yu-Gui Cui ◽  
Xing-Hai Wang ◽  
Yue Jia ◽  
Amiya Sinha Hikim ◽  
...  
Keyword(s):  
Heat Treatment ◽  
Cell Death ◽  
Germ Cell ◽  
Outcome Measures ◽  
Cell Apoptosis ◽  
Heat Exposure ◽  
Continuous Treatment ◽  
Semen Parameters ◽  
Testosterone Undecanoate ◽  
Germ Cell Apoptosis

Abstract Context: In rodents and monkeys, a combination of hormonal and physical agents accelerates germ cell death. Objective: A “proof of concept” study was performed to investigate whether addition of heat exposure or a progestin to an androgen induces germ cell death and more complete and rapid spermatogenesis suppression. Design and Settings: A randomized clinical trial was performed at academic medical centers. Participants: We treated four groups of healthy male volunteers (18 per group) for 18 wk: 1) testosterone undecanoate (TU) 1000 mg im (first dose), followed by 500 mg im every 6 wk; 2) submersion of scrota at 43 C in water for 30 min/d for 6 consecutive days; 3) TU plus heat; and 4) TU plus oral levonorgestrel (LNG) 250 μg/d. Main Outcome Measures: Semen parameters, testicular histology, and germ cell apoptosis were the main outcome measures. Results: Heat alone and TU plus heat suppressed sperm counts more than TU alone by wk 6. By wk 9, recovery began in the heat only group, whereas spermatogenesis remained suppressed in the TU plus heat group. Oral LNG plus TU suppressed spermatogenesis earlier and more severely than TU alone. At wk 2, significantly greater germ cell apoptosis occurred in heat and heat plus TU subjects, but not in subjects without heat treatment, compared with pretreatment subjects. By 9 wk, markedly smaller seminiferous tubule diameters and fewer spermatocytes and spermatids were noted in all 12 biopsies from men receiving TU, TU plus LNG, with most dramatic differences for the TU plus heat group, whereas no differences from pretreatment biopsies were observed in men who received heat treatment only. Conclusions: Heat causes a rapid and transient suppression of spermatogenesis. TU plus heat resulted in low-sperm output that was maintained by continuous treatment with TU. Addition of an oral progestin accelerated spermatogenesis suppression by TU alone. Increased germ cell apoptosis contributed to suppression of spermatogenesis.

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

2006 ◽  
Vol 91 (2) ◽  
pp. 539-545 ◽  
Author(s):  
Yanhe Lue ◽  
Christina Wang ◽  
Yi-Xun Liu ◽  
Amiya P. Sinha Hikim ◽  
Xue-Sen Zhang ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Apoptosis ◽  
Synergistic Effects ◽  
Recovery Period ◽  
Heat Exposure ◽  
Suppressive Effect ◽  
Controlled Study ◽  
Cynomolgus Monkeys ◽  
Germ Cell Apoptosis ◽  
Sperm Counts

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.

scholarly journals EXPRESSION OF BCL-2 AND BAX IN RHESUS MONKEY TESTIS DURING GERM CELL APOPTOSIS INDUCED BY TESTOSTERONE UNDECANOATE

2003 ◽  
Vol 49 (6) ◽  
pp. 439-447 ◽  
Author(s):  
Z.-H. ZHANG ◽  
X.-C. ZHOU ◽  
P. WEI ◽  
Z.-Y. HU ◽  
Y.-X. LIU
Keyword(s):  
Rhesus Monkey ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Testosterone Undecanoate ◽  
Germ Cell Apoptosis

Effects of whole-body heat on male germ cell development and sperm motility in the laboratory mouse

2016 ◽  
Vol 28 (5) ◽  
pp. 545 ◽  
Author(s):  
H. Wechalekar ◽  
B. P. Setchell ◽  
K. R. Pilkington ◽  
C. Leigh ◽  
W. G. Breed ◽  
...  
Keyword(s):  
Germ Cell ◽  
Sperm Motility ◽  
Cell Apoptosis ◽  
Heat Exposure ◽  
Male Germ Cell ◽  
Whole Body ◽  
Control Group ◽  
Germ Cell Apoptosis ◽  
Heat Treated ◽  
Body Heat

This study investigated the effects of high temperatures on male germ cell development and epididymal sperm motility of laboratory mice. In Experiment 1, adult males (n = 16) were exposed to whole-body heat of 37–38°C for 8 h day–1 for 3 consecutive days, whereas controls (n = 4) were left at 23–24°C. In Experiment 2, adult mice (n = 6) were exposed to 37–38°C for a single 8-h period with controls (n = 6) left at 23–24°C. Experiment 2 was conducted as a continuation of previous study that showed changes in spermatozoa 16 h after exposure to heat of 37–38°C for 8 h day–1 for 3 consecutive days. In the present study, in Experiment 1, high temperature reduced testes weights 16 h and 14 days after exposure, whereas by Day 21 testes weights were similar to those in the control group (P = 0.18). At 16 h, 7 and 14 days after exposure, an increase in germ cell apoptosis was noticeable in early and late stages (I–VI and XI–XII) of the cycle of the seminiferous epithelium. However, apoptosis in intermediate stages (VII–X) was evident 16 h after heat exposure (P < 0.05), without any change at other time periods. By 21 days, there were no significant differences between heat-treated groups and controls. Considerably more caspase-3-positive germ cells occurred in heat-treated mice 16 h after heat exposure compared with the control group (P < 0.0001), whereas 8 h after heat in Experiment 2, sperm motility was reduced with a higher percentage of spermatozoa showing membrane damage. In conclusion, the present study shows that whole-body heat of 37–38°C induces stage-specific germ cell apoptosis and membrane changes in spermatozoa; this may result in reduced fertility at particular times of exposure after heating.

Regulation of human male germ cell death by modulators of ATP production

2006 ◽  
Vol 290 (6) ◽  
pp. E1145-E1154 ◽  
Author(s):  
Krista Erkkila ◽  
Sauli Kyttanen ◽  
Marten Wikstrom ◽  
Kimmo Taari ◽  
Amiya P. Sinha Hikim ◽  
...  
Keyword(s):  
Cell Death ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Male Germ Cell ◽  
Germ Cell Apoptosis ◽  
Atp Production ◽  
Mitochondrial Inhibitors ◽  
Human Male ◽  
Induced Apoptosis

The understanding of testicular physiology, pathology, and male fertility issues requires knowledge of male germ cell death and energy production. Here, we induced human male germ cell apoptosis (detected by Southern blot analysis of DNA fragmentation, TUNEL, activation of caspases-3 and -9, and electron microscopy) by incubating seminiferous tubule segments under hormone- and serum-free conditions. Inhibitors of complexes I to IV of mitochondrial respiration, exposure to anoxia, and inhibition of F0F1-ATPase (with oligomycin) decreased the ATP levels (analyzed by HPLC) and suppressed apoptosis at 4 h. Uncoupler 2,4-dinitrophenol (DNP) and oligomycin combination also suppressed death at 4 h, as did the DNP alone. Inhibition of glycolysis by 2-deoxyglucose neither suppressed nor further induced apoptosis nor altered the antiapoptotic effects of the mitochondrial inhibitors. Furthermore, Fas system activation did not modify the effects of mitochondrial modulators. After 24 h, delayed male germ cell apoptosis was observed despite the presence of the mitochondrial inhibitors. We conclude that the mitochondrial ATP production machinery plays an important role in regulating in vitro-induced primary pathways of human male germ apoptosis. The ATP synthesized by the F0F1-ATPase seems to be the crucial death regulator, rather than any of the complexes (I-IV) alone, the functional electron transport chain, or the membrane potential. We also conclude that there seem to be secondary pathways of human testicular cell apoptosis that do not require mitochondrial ATP production. The present study emphasizes the role of the main catabolic pathways in the complex network of regulating events of male germ cell life and death.

scholarly journals EXPRESSION OF BCL-2 AND BAX IN RHESUS MONKEY TESTIS DURING GERM CELL APOPTOSIS INDUCED BY TESTOSTERONE UNDECANOATE

2003 ◽  
Vol 49 (6) ◽  
pp. 439-447 ◽  
Author(s):  
Z. -H. Zhang ◽  
X. -C. Zhou ◽  
P. Wei ◽  
Z. -Y. Hu ◽  
Y. -X. Liu
Keyword(s):  
Rhesus Monkey ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Testosterone Undecanoate ◽  
Germ Cell Apoptosis

Expression of Hsp70–2 in rhesus monkey testis during germ cell apoptosis induced by testosterone undecanoate

Contraception ◽  
2002 ◽  
Vol 66 (5) ◽  
pp. 377-382 ◽  
Author(s):  
Xin-Chang Zhou ◽  
Zhi-Hong Zhang ◽  
Zhao-Yuan Hu ◽  
Ru-Jin Zou ◽  
Yi-Xun Liu
Keyword(s):  
Rhesus Monkey ◽  
Germ Cell ◽  
Cell Apoptosis ◽  
Testosterone Undecanoate ◽  
Germ Cell Apoptosis
Sign in / Sign up

Export Citation Format

Share Document