Age-dependent reproductive and exocrine function after unilateral Testis Loss in C57BL/6 Mice.
Daniel E. Nassau, MD1, Eliyahu Kresch, BS2, Maria C. Suarez A., MD2, Shathiya Kulandavelu, PhD.2, Miguel A. Castellan, MD3, Himanshu Arora, PhD.2, Ranjith Ramasamy, MD2.
1Nicklaus Children's Hospital, Miami, FL, USA, 2University of Miami, Miami, FL, USA, 3Children's Urology Associates, Miami, FL, USA.
BACKGROUND: The sequela of unilateral testicular loss on male reproductive and exocrine function is unknown. Animal models demonstrate compensatory testicular hypertrophy if loss occurs before puberty; however, it is unclear how age of testis loss impacts compensatory growth and Testosterone (T) production. Using an animal model with C57BL/6 mice, we hypothesized that contralateral testicular compensatory hypertrophy and T production would be greater if a unilateral orchiectomy was performed at younger prepubertal age and absent if performed post-puberty.
METHODS: An abdominal approach unilateral orchiectomy was performed under isoflurane anesthesia in C57BL/6 laboratory mice at either the neonatal, prepubertal and post-pubertal periods between days of life (DOL) 2-4, 20-22 and 42-44, respectively. The experimental groups, as well as a control group who did not undergo any procedure were sacrificed after reaching physical maturity (DOL 80). Cardiac puncture was used to obtain T and LH levels by ELISA. Body and testis weight were recorded, and the long axis of the testis was measured with calipers. Each testis was evaluated histologically. Testis to body weight (TW/BW) ratio was calculated and a two-tailed t-test was used to determine statistical significance (p<0.05).
RESULTS: Median testis weight was highest in the neonatal group (n=7) at 110.5mg followed by prepubertal (n=8) at 103mg, both of which were significantly heavier than control group (n=5) at 91.1mg (p<0.0001, p<0.01, respectively). Neonatal weight was also significantly greater than the post-pubertal group (n=8) at 100.4mg (p<0.005). Only the median TW/BW ratio for the neonatal group, 0.040, was significantly higher than control, 0.033 (p<0.05). There was no significant difference in body weight, testis length in any group (Figure 1). Seminiferous tubule number, degree of spermatogenesis and Leydig cell concentration were similar in all groups. After controlling for outliers, T levels were not significantly different between the groups; however, LH levels were significantly higher in all experimental groups compared with control (Table 1).
CONCLUSIONS: Male reproductive and exocrine function compensate after unilateral testis loss through different mechanisms. Contralateral hypertrophy to maintain fertility only occurs when the loss is prepubertal and earlier age of loss may increase the degree of compensation. Conversely, T production is maintained after testis loss in all age groups, but higher LH levels were needed. Further work should focus on elucidating the underlying mechanisms that influence compensated testicular growth and the long-term effects of pituitary/testicular strain to maintain a eugonadal state. 
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