Fertility of rat epididymal sperm after chemically and surgically induced sympathectomy

Guanethidine, a chemical that selectively blocks sympathetic noradrenergic neurons, was used to investigate the role of sympathetic innervation in the fertility of rat epididymal sperm, using both natural mating and in utero insemination protocols. This animal model correlates, at least in part, with spinal cord injury (SCI) in men. Adult male rats were treated daily by i.p. injections, for 21 or 42 days, with 0 or 6.25 mg/kg guanethidine. To compare the effects of guanethidine-induced sympathectomy with those following surgically induced sympathectomy, the inferior mesenteric ganglion and the proximal hypogastric nerves were removed in another group of rats. Both chemically and surgically induced sympathectomy increased the weight of the epididymis and seminal vesicles/coagulating glands as well as the number and the transit time of cauda epididymal sperm. Neither serum testosterone levels nor LH was affected by treatment with guanethidine. Using natural mating, no litters were produced by guanethidine-treated rats. Chemically denervated rats failed to produce copulatory plugs or ejaculate into the uterus. However, distal cauda epididymal sperm from chemically or surgically denervated rats displayed normal fertilization ability (80%) using in utero inseminations. In addition, the sperm of denervated rats did not show abnormal sperm chromatin structure using an assay that detects DNA damage. We conclude that sympathectomy delays the transit of sperm through the cauda epididymidis and produces ejaculatory dysfunction but does not compromise sperm quality in the distal cauda epididymidis. Moreover, these data provide compelling evidence that there is no association between the prolonged transit time of sperm within the epididymis, i.e., pre-ejaculatory sperm aging, and the fertility of those sperm, which has important implications for artificial insemination using sperm from men with SCI

Bayesian methods for the cross-design synthesis of epidemiological and toxicological evidence

Systematic review and synthesis (meta-analysis) methods are now increasingly used in many areas of health care research. We investigate the potential usefulness of these methods for combining human and animal data in human health risk assessment of exposure to environmental chemicals. Currently, risk assessments are often based on narrative review and expert judgment, but systematic review and formal synthesis methods offer a more transparent and rigorous approach. The method is illustrated by using the example of trihalomethane exposure and its possible association with low birth weight. A systematic literature review identified 13 relevant studies (five epidemiological and eight toxicological). Study-specific dose-response slope estimates were obtained for each of the studies and synthesized by using Bayesian meta-analysis models. Sensitivity analyses of the results obtained to the assumptions made suggest that some assumptions are critical. It is concluded that systematic review methods should be used in the synthesis of evidence for environmental standard setting, that meta-analysis will often be a valuable approach in these contexts and that sensitivity analyses are an important component of the approach whether or not formal synthesis methods (such as systematic review and meta-analysis) are used. Copyright 2005 Royal Statistical Society.