Reproduction Abstracts

Sertoli cells (SC) are key initiators of testis development and have a fundamental role in spermatogenesis. However, it is uncertain how an acute reduction in SC number, in a hormone independent-manner at key points in development or adulthood, will impact testis function.

To induce acute SC-ablation at key points of testicular development, we used Cre-loxP recombinase technology and the expression of Diphtheria toxin and its receptor. We utilized these lines to determine i) the impact on testicular development and function arising from a reduction in SC numbers and ii) the capacity of the remaining SC population to compensate this reduction at different developmental stages.

When SC-ablation occurred during embryogenesis, tubular structure was absent at day 0, but recovered by day 9. However, daily sperm count and epididymal reserves were reduced in adulthood, consistent with previous studies showing a relationship between SC number and quantitative spermatogenesis.

When ablation was induced by >10 ng DTX post-puberty, disruption remained apparent 30 days post-ablation. Conversely treatment with <10 ng DTX failed to impact testicular architecture and function, suggesting a threshold of SC loss must be reached before testis function is affected. Throughout the study reduction in sperm number correlated to the extent of SC reduction.

We have demonstrated that an acute reduction in SC numbers negatively impacts adult sperm number and that testicular recovery appears to be age dependant. Further characterization will produce a unique model of subfertility, in which the hypothalamic–pituitary–gonadal axis is unaffected, allowing analysis of novel therapeutics for improving sperm production and male fertility.