Developing fertility control for rodents: a framework for researchers and practitioners

Fertility control is often heralded as a humane and effective technique for management of overabundant wildlife,including rodents.The intention is to reduce the use of lethal and inhumane methods,increase farm productivity and food security as well as reduce disease transmission,particularly of zoonoses.We developed a framework to guide researchers and stakeholders planning to assess the effectiveness of a potential contraceptive agent for a particular species.Our guidelines describe the overarching research questions which must be sequentially addressed to ensure adequate data are collected so that a contraceptive can be registered for use in broad-scale rodent management.The framework indicates that studies should be undertaken iteratively and,at times,in parallel,with initial research being conducted on(1)laboratory-based captive assessments of contraceptive effects in individuals;(2)simulation of contraceptive delivery using bait markers and/or surgical sterilization of different proportions of afield-based or enclosure population to determine how population dynamics are affected;(3)development of mathematical models which predict the outcomes of different fertility control scenarios;and(4)implementation of large-scale,replicated trials to validate contraceptive efficacy under various management-scalefield situations.In some circumstances,fertility control may be most effective when integrated with other methods(e.g.some culling).Assessment of non-target effects,direct and indirect,and the environmental fate of the contraceptive must also be determined.Developing fertility control for a species is a resource-intensive commitment but will likely be less costly than the ongoing environmental and economic impacts by rodents and rodenticides in many contexts.

Acute oral toxicity of zinc phosphide:an assessment for wild house mice(Mus musculus)

Irregular plagues of house mice,Mus musculus,incur major economic impacts on agricultural production in Australia.The efficacy of zinc phosphide(ZnP),the only registered broadacre control agent for mice,is reported as increasingly variable.Have mice become less sensitive over time or are they taking a sub-lethal dose and develop-ing aversion?In this laboratory study,the sensitivity of mice(wild caught;outbred laboratory strain)was assessed using oral gavage of a range of ZnP concentrations.The estimated LD50 values(72–79 mg ZnP/kg body weight)were similar for each mouse group but are significantly higher than previously reported.The willingness of mice to consume ZnP-coated grains was determined.ZnP-coated grains(50 g ZnP/kg grain)presented in the absence of alternative food were consumed and 94%of wild mice died.Mice provided with alternative food and ZnP-coated wheat grains(either 25 or 50 g ZnP/kg grain)consumed toxic and non-toxic grains,and mortality was lower(33–55%).If a sublethal amount of ZnP-coated grain was consumed,aversion occurred,mostly when alternative food was present.The sensitivity of wild house mice to ZnP in Australia is significantly lower than previously assumed.Under laboratory conditions,ZnP-coated grains coated with a new higher dose(50 g ZnP/kg grain)were readily consumed.Consumption of toxic grain occurred when alternative food was available but was decreased.Our unambiguousfindings for house mice indicate a re-assessment of the ZnP loading for baits used for control of many rodents around the world may be warranted.

Anti-fertility effect of levonorgestrel and quinestrol in Brandt’s voles(Lasiopodomys brandtii)

The combination of levonorgestrel and quinestrol(EP-1)has been shown to have anti-fertility effects on several wild rodents,but the mechanism underlying these effects is poorly understood.We investigated the effects of EP-1 and each of its components,levonorgestrel(P)and quinestrol(E),on the fertility of Brandt’s voles(Lasiopodomys brandtii)by using a gastric gavage method.The doses for EP-1,E and P were 1,0.34 and 0.66 mg/kg body weight,respectively.Male voles(n=98)were treated daily for 5 or 14 days,then the testes and epididymides were collected,weighed and examined histologically at 30(D30),60(D60)or 90(D90)days after the end of treatment.Four males were allowed to mate with normal females at D90.Female voles(n=75)were treated for 3 days and a further 3 days after a 7-day interval.The uteri and ovaries were weighed and examined histologically at 15(D15),30(D30)or 75(D75)days after the end of treatment.Each of three females were mated with fertile males at D30 and D75,respectively.Our results indicated that quinestrol(E)significantly decreased the sperm numbers in the testes as well as the weight of the testes and epididymides,with both of these tissues showing obvious structural abnormalities,and significantly reduced the litter size and the pup weight for females mated with males of the E treatment group.For female voles,treatment with E,P or EP-1 resulted in no marked influence on the fertility status.These data indicate that quinestrol(E)alone has a significant anti-fertility effect on male Brandt’s voles,but is ineffective in combination with levonorgestrel(P).

The status of fertility control for rodents—recent achievements and future directions

Management of overabundant rodents at a landscape scale is complex but often required to sustainably reduce rodent abundance below damage thresholds.Current conventional techniques such as poisoning are not species specific,with some approaches becoming increasingly unacceptable to the general public.Fertility control,first proposed for vertebrate pest management over 5 decades ago,has gained public acceptance because it is perceived as a potentially more species-specific and humane approach compared with many lethal methods.An ideal fertility control agent needs to induce infertility across one or more breeding seasons,be easily delivered to an appro-priate proportion of the population,be species specific with minimal side-effects(behavioral or social structure changes),and be environmentally benign and cost effective.To date,effective fertility control of rodents has not been demonstrated at landscape scales and very few products have achieved registration.Reproductive targets for fertility control include disrupting the hormonal feedback associated with the hypothalamic-pituitary-gonadal axis,gonad function,fertilization,and/or early implantation.We review progress on the oral delivery of various agents for which laboratory studies have demonstrated efficacy in females and/or males and synthesize progress with the development and/or use of synthetic steroids,plant extracts,ovarian specific peptides,and immunocontracep-tive vaccines.There are promising results forfield application of synthetic steroids(levonorgestrel,quinestrol),chemosterilants(4-vinylcyclohexene diepoxide),and some plant extracts(triptolide).For most fertility control agents,more research is essential to enable their efficient and cost-effective delivery such that rodent impacts at a population level are mitigated and food security is improved.

Reproductive responses of rice field rats(Rattus argentiventer)following treatment with the contraceptive hormones,quinestrol and levonorgestrol

The ricefield rat,Rattus argentiventer,is a significant pest of rice in Southeast Asia.Fertility control methods have the potential to provide safe and effective alternatives to control methods that often include indiscriminate use of rodenticides or electric barriers.The aim of this laboratory study was to assess uptake of bait coated with different concentrations of the contraceptive hormones,quinestrol(E)and levonorgestrel(P),delivered alone and in combination(i.e.EP-1)and determine the short-term effects on reproductive parameters of adult male and female R.argentiventer.In Experiment 1,2 concentrations of E,P,and EP-1(10,20 ppm)were fed to groups of wild-caught rats for 7 days.In females,both E and EP-1 induced uterine edema.In males,EP-1 reduced epididymis and seminal vesicle weights and lowered sperm motility.However,these responses were inconsistent due to low bait acceptance,especially with increasing concentrations.In Experiment 2,EP-1(0,20,50,100 ppm)was administered by oral gavage daily for 7 days to male R.argentiventer.There were significant reductions in epididymal and seminal vesicle weights for all oral doses of EP-1,in sperm counts for the 50 ppm dose,and in sperm motility for the 20 and 50 ppm doses compared to the control group.To select the optimum dose of EP-1,we must address the poor acceptance of contraceptive-coated baits by ricefield rats.Further research is required to improve the palatability of EP-1 and to test its uptake underfield conditions.

Fertility control of rodent pests: recent developments from lab to field

This special issue of Integrative Zoology(the official journal of the International Society of Zoological Science and the Institute of Zoology,Chinese Academy of Sciences)comprises a series of papers,aspects of which were presented at the 23rd International Congress of Zoology,a virtual meeting for participants between November 22 and 24,2021.The symposium topic at the virtual conference was“Fertility control of rodent pests for better agriculture,ecosystems and human health.”