contraception methods in captive wildlife.pdf

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University of Nebraska - Lincoln

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Contraception in Wildlife Management USDA National Wildlife Research Center Symposia

10-26-1993

Te Development of Contraceptive Methods forCaptive Wildlife

Cheryl S. Asa

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Asa, Cheryl S., "Te Development of Contraceptive Methods for Captive Wildlife" (1993).Contraception in Wildlife Management.Paper 2.hp://digitalcommons.unl.edu/nwrccontraception/2
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The Development of ontraceptive Methodsfor aptive WildlifeC h e r y l S Asa

Ab stra ct: Contraception has become critical in managingzoo populations, both to limit production of surplus animalsand to promote genetic health. One role of theContraception Advisory Group, formed in 1989 is tocoordinate research to develop new contraceptive methods.Because melengestrol acetate (MGA) implants, which havebeen used by zoos for almost 2 years, recently have beenassociated with uterine pathology in felids, several newcontraceptive techniques are being evaluated. Theseinclude other steroid hormone formu lations, such as thebirth control pill Depo-Provers,@ the Norp lanm implant, andMGA added to feed; bisdiamine, an oral male contraceptive;zona pellucida (ZP) vaccine; and vas plugs. Bisdiaminereversibly blocked spermatogenesis while sparingtestosterone in its first test in gray wolves. ZP vaccine has

IntroductionThe modern zoo now faces the consequences ofbeco ming too successful at breeding and m aintainingthe an imals in its care. Advances in husbandry,nutrition, and m edicine have resulted in more birthsan d longer lives for most captive species. The m ajorbene fit of this success is that these ca ptive popu la-tions can be self-perpetuating and not dependent onimpo rtation of animals from the wild. However, du e tolimited space and resources, zoos cannot allowuncontrolled reproduction.

In addition, zoos give high priority to propergen etic man ageme nt, that is, reduction of inbreedingan d balanced genetic representation of the foundersof captive populations. Both genetic managem ent andlimiting production of surplus anima ls are beingaccomplished through contraception.Although physical separation of males andfemales can prevent un wanted conceptions, mostzoo s consider this an undesirable measure. Not onlyca n such an arrangemen t be stressful for species inwhich males and females typically associate, loneanim als present an un natural view of that species tothe visit ing public. A prim ary mission of zoos iseducation, a mission that is better served by m aintain-ing animals in social groupings which are a s represen-tative as possible of the orga nization that would occurin the wild.

been effective n preventing births in a variety of species ofhoofstock, primates, and carnivores; however, long-termdeleterious effects on the ovaries have been found in somecontrolled trials. Injectable vas plugs that conform to theshape of the vas make it possible to success fully reat awide variety of species ; reversal trials are currentlyunderwav. As research efforts continue, we hODe to ex~andour collaborations with scientists working on contracepiivedevel0Dment for humans. co m~a nion nimals and wildlife.to better make use of the limited resources available forthese investigations.Keywo rds: contraception, captive animals, zoo, vas p lugs,bisdiamine, indenopyridine, zona pellucida vaccine, GnRHagonist, LHRH vaccine

In recognition of the importance of contraceptionin responsible anim al manage ment, the Am ericanAssociation of Zoos a nd Aquariums a pproved forma-tion of the Co ntraception Advisory G roup in 19 89.Comp osed of zoo curators, veterinarians, and repro-ductive physiologists, the grou p surveys the use ofcontraception in zoos for inclusion in a computerizeddata ba se, advises zoo personnel, and initiates andcoordinates rese arch into alternative m ethods.

The International Wildlife Contraception Da ta-base , housed at the St. Louis Zoo, was developed andis maintained by Ingrid Porton and B etsy Hornbeck ofthe Contraception Advisory Group. Begun in 1990and updated from yearly surveys, it currently containsmore than 2,000 complete records on 184 species andserves as a resource for zoo animal manag ers and forresearchers.

Contraception of captive wildlife in zoos beg an inthe mid-1970 s. After preliminary tests with lions andtigers (Seal et al. 1976, Seal and P lotka 1978) com-paring medroxyprogesterone acetate (P rovera ,BTheUpjohn Co., Kalamazoo, MI, USA) and m elengestrolacetate (M GA , also Upjohn), MGA in sil icone implantform was selected as the more suitable. Of the morethan 80 percent o f North American zoos that reportedusing contraception (Po rton et al. 1990 ), most use theMG A implant.


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However, concern has arisen about possiblepathology in proges tin-treated carnivores Kollias1988, Kollias et al. 1984) because deleterious effectshave been associated with progestin use in domesticdogs and cats reviewed in Asa and Porton 1991, Asaet al. 1996). Indeed, histological examination of uterifrom MGA -treated felids has revealed significantlymore pathology tha n those from untreated felidsMunson and M ason 1991).

No comparable effects are expected i n primates,based on the extensive studies that have been con-ducted in laboratory prima tes, as well as decades o fproges tin adm inistration to human females. In gen-eral, birth control methods that have b een approvedfor human use should be safe and effective for nonhu-ma n primates. Birth control pills combination proges-tin and estrogen, various formu lations commerciallyavailable), Depo-Provera, Norplant levonorgestrelimplan t system, Wyeth-Ayerst, Philadelphia, PA,USA ), and intrauterine devices have been use d inprimates , especially in the great apes Porton et al.1990). However, few data exist on progestin effects inungulates and other mam mals.

A number of research trials are under way toevaluate new app roache s with the hop e of providing abroade r selection of contrace ptives, especially alterna-tives to the progestin-base d formulations for carnivo res.These include vas plugs, the antispermatogenic com-pounds bisdiamine and indenopyridine, and short-termDepo-Provera or seasonal breeders. Additional work isfocusing on specific aspects of MGA treatment. For adiscuss ion of the progress of zona pellucida trials inzoos, see Kirkpatrick et al., this volume.

Melengestrol cetateAs mentioned, MG A is the most frequently usedcontraceptive for captive mam mals. MGA is incorpo-rated into silicone rods by E. D. Plotka MarshfieldMedical Research Foundation, Marshfield, WI) anddistributed to zoos throughout the world. Wheninserted subcutaneously, the implants provide effec-tive contraception for at least years Porton et al.1990). The only side effec t noted in primates has

been weight gain Portugal and Asa 1995), which isalso common in human females treated withprogestins.

Because of conce rn about possible effects onsocial behavior, a study was condu cted with a troop ofhamadryas baboons Papio hamadryas) at the St.Louis Zoo Portugal and Asa 1995 ). Administration ofMGA was not assoc iated with social disruption.Treated females w ere involved in fewer affiliativeinteractions, but there was no increase in aggressioncompared to con trol animals.Although MGA implants have been effective in awide range of monkeys and apes, some N ew Worldprimate species have proven resistant. Bec ause theyhave naturally high levels of endoge nous steroids,these species may require larger exogenous doses toachieve contraception. Research is being conductedto test this hypo thesis E. Plotka, pers. com m.).

Recognizing that individual capture and immobili-zation for implant insertion may be inadvisable insom e situations, Bronx Zoo veterinarians B. Raphael,pers. comm.) have tested adding MG A to feed forherds of antelope and deer. Although this procedu reis generally successful, drawbacks include contracep-tive failure in some su bordinate anim als that appa r-ently did not ingest a sufficient dose and alteration ofthe antler cycle in male barasinga Cervus duvauceli).

Pathological effects of MG A and relatedprogestins are being investigated by Linda M unsonUniversity of Tennessee, Knoxville). Early work

concentrated on reproductive tracts of felids Munsonand M ason 1991), and research is now extending toother carnivores and primate s. In general, progestinshave bee n found to stimulate growth of the uterinelining of felids an d canids, resulting in hyperplas ia,pyometra, and neoplasia reviewed in Asa and P orton1991). Effects of dosage, length of treatment, and ageduring treatment a re currently being studied.


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also can find application in supp ression of aggressionin some individuals.

Lupron Depot also has b een given to females tosuppress cyclicity. However, beca use agonists firststimulate the endocrine cascade that results in ovula-tion, administration to induce d ovulators, such as thefelids, may stimulate ovulation and pseudopregnancybefore suppressing cycles by negative feedback.

Although a nalogues show p romise in providingthe equivalent of reversible chemical castrations, theircurrent cost prohibits for widespread use. Long-termdelivery also is a problem. Because these compoundsare not orally active an d do not follow the samediffusion dy nam ics as steroids, traditional deliverymethods such as sil icone imp lants have not beeneffective. Both a silicone elastomer ma trix an d areservoir system are being tested (Vickery et al.1989).

LHRH VaccineImmunization against LHRH can provide contraceptionfor both males and females (Fraser 1986). LHRHinitiates the casc ade of ho rmon al even ts that results intestosterone and sperm production in males and inproduction of estrogen and progesterone and ovula-tion in females. Beca use this vaccination wouldaccomplish the equivalent of a reversible chemicalcastration , it can be especially ap prop riate for malesto suppress testosterone and thus aggression a nd forfemale carnivores to completely suppress secretion ofprogesterone. Vaxstrate, an LHRH vaccine that iscomm ercially available in Australia (Arthu r WebsterPty. Ltd., New So uth Wales, Australia) for dom esticcows (Hoskinson et al. 19 90), has also been used withsuccess in some exotic species at the Western Plainsan d Perth zoos (D. Blyd e and S. Haigh, pers. comm.).In this country, both The Population Council in Ne wYork and Colorado State University are developingLHRH vaccines.

isdiamineAll the steroid hormone prepa rations in use in zoostarget the female. Howeve r, if prevention of reproduc-tion is desired in polygynous social groups, it is moreefficient to treat the ma les than the females. Thebisdiamine W IN 18,446 (Sterling Winthrop,Rensselaer, NY, USA) was tested in the early 1960 sas a birth control pill for m en. It works by selectivelyinterfering with sperm atogenesis but not testosteroneproduction. Although initial trials demo nstrated thedru g to be effective, safe, an d reversible, it was soondiscove red to interact with an e nzym e that detoxifiesalcohol. Thus, m en taking bisdiamine w ho then drankalcohol becam e il l, making the com pound unsuitablefor general marketing. Because we assume that wecan prevent alcohol consum ption in captive animals,bisdiamine may be a feasible contraceptive alternativefor this application.

The first test of bisdiamine in a wildlife specieswas con ducted with a captive colony of gray wolves(Asa et al. 1995). Daily administration in ground m eatat a dose of 20 0 m glkg suppressed spermatogenesiswithout affecting mating behavior. In the subsequ entbreeding season, seme n samples of the previouslytreated m ales were com parable to those of controls,confirm ing reversibility.

lndenopyridineThis d rug (Research Triangle Institute, ResearchTriangle Park, NC, USA) is similar to bisdiamine inthat it is orally active and blocks sperm productionwithout interrupting testosterone secretion. To date, ithas been tested only in rodents (Fail et al. 1991,Gurtler and Donatsch 1979, Hodel and Suter 19 78),so the extent of its efficacy and safety h as not beenadequately determined. A dose respon se trial withdome stic cats, as a mo del for exotic felids, is currentlybeing conducted (Fail et al., unp ubl.)


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Vas PlugsL.J.D. Zaneveld and I investigated vas plugs. Siliconeinjected into the vas deferens, the tube carrying spermfrom the testis, hardens to form a barrier that preventsthe passage of sperm. Plugs were placed in 59mamma ls, including marsup ials, felids, primates, andungu lates, at 17 different zoos. Early use of thepreformed plug (Zaneveld et al. 1988), which is also inclinical trials with humans, proved inadequate for therange of vas sizes encoun tered in zoo animals. Theinjectable plugs were successful in blocking passageof sperm, bu t fertility was not restored after removal.

References itedAsa, C. S.; Porton, 1 1991 Concerns and prospectsfor contraception in carnivores. Proceedings of theAmerican Association of Zoo Veterinarians: 298-303.Asa, C. S.; Po rton, I ; Plotka, E D.; Baker, A. 1996Contraception. In: Lumpkin, S.; Allen, M ., eds. Wildmam mals in captivity, vol. 1 Principles and techniquesof captive mana gement, sec. A: Captive propaga tion.Chicago: University of Chicago Press.Asa , C. S.; Zane veld , L.J.D.; Mu ns on , L.; Ca llaha n,M.; Byers, A. P. 1996 Efficacy, safety and reversabilityof a bisdiamine as a ma le-directed oral contraceptivein gray wolves (Can is lupus). Journal of Zoo andWildlife Medicine 27 : 501-506.Fail, P.A.; Anderson, S. A,; Want, M. C.; Lee, D.;Coo k, C. E. 1991 Response of mouse testis toSandoz 20-438 (S2-43 8). Biological Reproduction,Suppl. 42: 175.Fras er, H. M. 1986 LHRH immunoneutralization:basic studies and prospe cts for practical applicationIn: Talwar, G. P., ed. immunological approaches tocontracep tion and promo tion of fertility. New York:Plenum Press: 125-138.Gurtler, J ; Donatsch, P 1979 Effects of two struc-turally different antispermatogenic compounds on thesynthesis of steroids in rat testes. Archives of Toxicol-ogy, Suppl. 2: 381-385.

Hodel, C.; Suter, K. 1978 Reversible inhibition ofspermatogenesis with an indenopyridine (20-438).Archives of Toxicology, Suppl. 1 323-326.Hos ki nso n, R. M.; Rigby, R.D.G.; Ma ttne r, P. E ;Huynh, V. L.; D'Occhio, M.; Neish, A ; Trigg, T. T.;Moss, 8 A,; Lindsey, M. J ; Coleman, G. D.;Schwartzkoff, C. L. 1990 Vaxstrate: an a nti-repro-ductive vaccine for cattle. Australian Journal of Bio-technology 4: 166-1 70.Kollia s, G. V., Jr. 1988 Complications of progestogencontraception in exotic felids. P roceedings of theAmerican A ssociation of Zoo Veterinarians: 149-1 52 .Ko llias, G. V., Jr.; Calderwood-Mays, M. 6 ; Short ,8 G. 1984 Diabetes mellitus and abdominal adeno-carcinoma in a jaguar receiving mege strol acetate.Journal of the Am erican Veterinary Medicine Associa-tion 185: 1383-1 386.La br ie , C.; C usan , L.; Plante , M.; Lap oint e, S.;Labrie, F 1987 Analysis of the androgenic activity ofsynthetic progestins currently used for the treatmentof prostate cancer. Journal of Steroid B iochemistry 28:379-384.Mu nso n, L.; Mason , R. J 1991 Patholog ical findingsin the urteri of progestogen-im planted exotic felids.Proceedings of the American Association o f ZooVeterinarians: 31 1-312.Porton, I ;Asa, C. S.; Baker, A. 1990 Survey resultson the use of birth control methods in primates andcarnivores in North A merican zoos. In : Proceedings ofthe annual conference of the American Association ofZoological Parks and Aquariums; [date and place ofmeeting unknown.] [Place of publication unknown]:American Association of Zoological Parks and Aquari-ums: 489-497.Portugal, M. M.; Asa, C. S. 1995 Effec ts of chronicmelengestrol acetate contraceptive treatment ontumescence, body weight, and sociosexual behaviorof hamadryas baboons (Papio hamadryas). ZooBiology 14: 251-259.Seal, U. S ; Barton, R.; Mather, L.; Olberding, K.;Plotka, E. D.; Gray, C. W. 1976 Hormonal contracep-tion in captive female lions (Panthera leo . Journal ofZoo Animal Medicine 7: 12-20.

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Seal U. S.; Plotka E. D. 1978. Baseline hematologyserum chemistry and hormo ne data for captive tigers.In: First international symposium on the managementand breeding of the tiger; [data and loca tion of sympo-sium unknown]. [Publisher unknown]: 174-191.Teunissen G.H.B. 1952. The development of endo-metritis in the dog and the effect of oestradiol andprogesterone on the uterus. Acta Endocrinology 9:407-420.Vickery B. H.; McRae G. I ; Goodpasture J. C ;Sanders L. M. 1989. Use of potent LHRH analoguesfor chronic contraception an d pregnancy termination indogs. Journal of Reproductive Fertility Suppl. 39:175-187.Zaneveld L.J.D.; Burns J. W.; Beyler S. A.; DepelW.; Shapiro S. W. 1988. Development of a potentiallyreversible vas deferens occlusion device and evalua-tion in primates. Fertility and Sterility 49: 527-533.

Directory of PersonalCommunicationsBlyde David. Western Plains Zoo New SouthWales Australia.Haigh Stephanie. Perth Zoo South Perth WesternAustralia.Plotka Ed. Marshfield Medical Research FoundationMarshfield WI 54449 U.S .A.Raphael Bonnie. Animal Med ical Center Bronx ZooNewYork NY 10460 U.S.A.

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