Paternal Exposure to Carbamazepine Impacts Zebrafish Offspring Reproduction Over Multiple Generations.

Chronic low-concentration chemical exposures may have both direct health outcomes on adults and indirect effects on their offspring. Using zebrafish, we examined the impacts of chronic, low-concentration carbamazepine (CBZ) exposure on a suite of male reproductive endpoints in the parents and four generations of offspring reared in clean water. CBZ is one of the most frequently detected pharmaceutical residues in water, is a histone deacetylase inhibitor in mammals, and is reported to lower androgens in mammals and fish. Exposure of adult zebrafish to 10 µg/L CBZ for 6 weeks decreased reproductive output, courtship and aggressive behaviors, 11-ketotestosterone (11KT), and sperm morphology but did not impact milt volume or sperm swimming speed. Pairwise breeding generated lineages of offspring with both parents exposed and two lineages where only one parent was exposed; the control lineage had unexposed parents. Reproductive output and male reproductive indices were assessed in F1-F4 offspring to determine whether parental CBZ exposure had transgenerational impacts. The offspring of CBZ-exposed males had lower 11KT, reproductive output, altered courtship, aggression, and sperm morphology compared to the lineage from unexposed parents. Our results indicate that parental carbamazepine exposure history impacts the unexposed progeny up to the F4 generations and that paternal, but not maternal, exposure is most important for the reproductive health of male offspring.

Parental gemfibrozil exposure impacts zebrafish F1 offspring, but not subsequent generations.

Gemfibrozil (GEM) is a fibrate lipid regulator and one of the most commonly occurring fresh water pharmaceuticals. The negative effects of fibrates including GEM on fish reproduction have been frequently reported including effects of F0 GEM exposure on reproduction of the unexposed F1 offspring. We predicted that chronic, direct exposure of zebrafish with low concentrations of GEM would adversely affect parental male reproduction and unexposed offspring for multiple generations. Adult zebrafish were exposed to 10 µg/L GEM for 6 weeks and a range of reproductive indices were analyzed. The F1-F4 offspring were reared in clean water from 3 distinct lineages where only a single or both parents were exposed and compared to a control lineage where parents were unexposed. Reproductive indices were examined in unexposed F1-F4 offspring to test the hypothesis of multi- or trans- generational impacts. Exposure to GEM caused a decline in breeding success and mean embryo production in F0 parents and a reduction in whole body 11-ketotestosterone (11-KT), altered male courtship, aggression and sperm morphology. Our results indicate that paternal exposure alone is sufficient to result in reproductive effects in unexposed male offspring but that effects are mostly limited to F1. We suggest that GEM may act as a reproductive endocrine disruptor in fish and that chronic exposure reduced male reproductive fitness but not over multiple generations.