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REVIEW: CONTRACEPTION CHALLENGES IN 109

Int. Zoo Yb. (2010) 44: 109–120 DOI:10.1111/j.1748-1090.2009.00107.x

Reproductive management in captive and wild canids: contraception challenges S. M. BOUTELLE1 & H. J. BERTSCHINGER2 1AZA Wildlife Contraception Center at the Saint Louis Zoo, 1 Government Drive, St Louis, Missouri 63110, USA, and 2Section of Reproduction, Department of Production Studies, University of Pretoria, Private Bag X04, Onderstepoort 0110, E-mail: [email protected]

Managing reproduction for Canidae is a chal- working with them. One area of focus is lenge for zoological institutions and wildlife sanctuaries. reproductive control, which is essential for There are four basic options for contraception: separation of sexes, surgical procedures, immunological and hormo- population management in captivity. Cur- nal methods. Animal managers face potential challenges rently it is known that all temperate Canidae for each option, and advantages and disadvantages species are monoestrus and usually seasonal, should be taken into consideration when making a which can influence the management styles decision. This paper evaluates four common Canidae implemented for controlling reproduction species with results from hormonal monitoring: Gray lupus/Mexican gray wolves Canis lupus (Asa et al., 1990). These physiological differ- baileyi, Maned wolves Chrysocyon brachyurus, Fennec ences between Canidae and other zerda and African wild pictus. make it a challenge to develop a consistent Special focus is given to individuals treated with the plan for contraception practices. Controlling gonadotropin-releasing hormone (GnRH) agonist, Supre- lorins. To date there are considerably more data for reproduction using reversible contraception African wild dogs than other canids, as extensive field is just one tool towards maintaining healthy observations are available for this species. Therefore, and well-managed groups in zoological African wild dogs are more extensively covered in this institutions. paper. GnRH agonists have been designated the safest There are four potential methods of repro- reversible method of contraception for carnivores and so continued studies are important. Results outlined below ductive control of canid species in captivity. demonstrate individual dosing differences that occur not These are separation of sexes, surgical proce- only across species but also between similar individuals. dures, immunological and hormonal meth- Although dosing and duration of efficacy still need ods. The feasibility for separation of sexes as further investigating, GnRH agonists are still considered to be the safest and most appropriate method available. a method depends on social behaviour of the As evident in this paper, contraception is a much-needed species and availability of enclosures in a tool for reproductive management. facility. Some can be separated without impacting social behaviour whereas Key-words: African wild ; Canidae; contraception; in many Canidae species, such as the Black- ; GnRH agonists; maned ; Mexican gray wolf; Suprelorins. backed Canis mesomelas that occurs in pairs, this would disrupt social behaviour (R. INTRODUCTION Harrison-White, pers. comm.). Separating sexes to prevent breeding is an effective The Canidae has a wide range of method of contraception. However, there are social and physiological mechanisms that are strong arguments against this management unique to this taxonomic group (Asa et al., tool because not only are social groups dis- 1990). Managing these species in captivity rupted but also reintroducing the individuals can be a challenge and it is important that later can cause aggression in the group as these mechanisms are taken into considera- hierarchy is reestablished (H. J. Bertschinger, tion for the welfare of the animals and those unpubl. data; see also Maisch, 2010).

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London 110 AND CANIDS

Another option for some zoological institu- again, investigations in Domestic dogs have tions may be to house ‘same-sex’ groups yielded positive results (< dogs, Jung et al., together in order to manage their collections 2005; < and , dogs, Walker et al., 2007) with and prevent unplanned births (van Heerden, a possible application to wild canids in the 1986; van Heerden et al., 1996; H. J. future. Bertschinger, unpubl. data). Reversible hormonal contraception pro- There are two surgical approaches: gona- ducts are available in a variety of delivery dectomy of both genders and vasectomy of systems including implants, injections and the < or salpingectomy of the ,. The former oral formulations. The two most commonly may disrupt social behaviour whereas the used hormonal products are synthetic proges- latter leaves the gonads and, therefore, sex tins [Depo-Proveras and melengestrol acet- steroid-related behaviours intact. Both ap- ate (MGA) implants] and GnRH agonists proaches are, for practical purposes, irrever- (Suprelorins/Suprelorin 12s and Luprons). sible; however, for individuals with little Table 1 summarizes the canid species known genetic value this may be irrelevant. Housing to have been treated with the more common surgically sterilized individuals together has contraceptive methods: progestins and GnRH been successful in many species without agonists [Association of Zoos and Aquariums behavioural complications. An example of (AZA) Wildlife Contraception Center this is the Lycaon pictus, (WCC), Saint Louis Zoo, MO, USA, data- where ,, subjected to salpingectomy were base]. Historically progestins have been used housed with intact << (H. J. Bertschinger, on a wide range of species; however, recently unpubl. data). There is evidence that repeated they have been found to induce uterine, infertile oestrous cycles, which will occur and hepatic pathology with after both vasectomies and salpingectomies, long-term treatment in felids and most likely may lead to the endometrial hyperplasia– other species (Asa & Porton, 2005; pyometra complex (H. J. Bertschinger, un- Munson, 2006). The recent publication by publ. data). All the pros and cons should be Moresco et al. (2009) provides evidence that considered before deciding to use such a MGA may have a role in the development of permanent method. endometrial hyperplasia in canids. According Immunocontraception for the control of to recommendations available through the reproduction in canid species has received AZA WCC (http://www.stlzoo.org/contra little attention to date. Sperm antigens as ception) the current safest method for all immunogens has been investigated in the carnivores is Suprelorins, which is a slow- Vulpes vulpes and success rates of release formulation with deslorelin as the up to 75% have been achieved (Boue´ et al., active GnRH agonist. GnRH agonists act at 2002). This level of contraception, however, the level of the adenohypophysis where they is insufficient for use in captive populations. inhibit the release of follicle stimulating hor- Porcine zona pellucida proteins have been mone and luteinizing hormone thus blocking used to induce infertility in , Domestic dogs the down-stream effects of these gonadotro- Canis lupus familiaris (Fayrer-Hosken et al., phins (Wright et al., 2001; Trigg et al., 2006). 2000). In the Domestic dog, however, the Accordingly, they are effective in both sexes humoral response is accompanied by a cell- of many species (Trigg et al., 2001; Wright mediated response with resulting destruction et al., 2001). of ovarian follicles and permanent sterility as The first deslorelin products for use in the final outcome (Fayrer-Hosken et al., wildlife became available as 3 and 6 mg 2000). The method with the most potential, a slow-release implants (Peptech Animal gonadotropin-releasing hormone (GnRH) Health Pty Limited). These early implants vaccine, has not been investigated for wild were not formulated by release time but canids. Besides being reversible it could rather doses made for different-sized dogs potentially be used in both genders. Once (Trigg et al., 2001; Junaidi et al., 2009).

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London REVIEW: CONTRACEPTION CHALLENGES IN CANIDAE 111

Accordingly, in the early wild carnivore bility. As more individuals are treated, dosing work, dose used was based on the sizes of will become more defined and reversibility the target animals. For example, 12 mg information will be available. (2 6 mg) was used for African lionesses leo while one 6 mg implant was ANIMALS TREATED used to down-regulate jubatus and African wild dogs (Bertschinger The Canidae species for which significant et al., 2001, 2006, 2008). In 2005, two new information is available are Gray wolves formulations became available; known as Canis lupus/Mexican gray wolves Canis Suprelorins (4 7 mg) and Suprelorins12 lupus baileyi, Maned wolves Chrysocyon (9 4 mg) (Peptech Animal Health Pty Lim- brachyurus, Fennec fox Vulpes zerda and ited), and both are registered in , African wild dogs. These species currently New Zealand and . The 4 7 mg im- have been treated most commonly with Su- plant was created to have a duration of effect prelorins, according to AZA WCC. African for at least 6 months and the 9 4 mg implant wild dogs have not only been treated in North for at least 12 months. Trigg et al. (2006) American zoos but also individuals have been describes these new formulations and their monitored consistently in South Africa, at applications for the Domestic dog. The Ann van Dyk Centre (formerly Suprelorins implants have become widely the de Wildt Cheetah and Wildlife Centre) available and the focus of many research and the National Zoological Gardens in Pre- projects evaluating efficacy, safety and rever- toria. Suprelorins implants are manufactured sibility. Although Suprelorins is the most for use in Domestic dog contraception man- commonly utilized GnRH agonist, Luprons agement and one implant is sufficient for each depot is another option for those individuals dog, irrespective of the size of the individual that need to be darted for treatment. However, (product insert, Peptech Animal Health Pty Luprons is an approved drug for managing a Limited). In previous alternative doses number of reproductive issues and, (3 and 6 mg) were available. At this time therefore, dosing may be cost-prohibitive Suprelorins is available in two sizes (4 7 to zoos and small institutions (Plosker & and 9 4 mg), which are formulated for Do- Brogden, 1994; Wilson et al., 2007). The mestic dogs and have a duration of effect for a injectable progestin, Depo-Proveras, is ad- minimum of either for 6 or 12 months. How- ministered typically as an interim method ever, exotic carnivores may have different and not as often for long-term suppression physical and physiological demands, there- because of its potential side effects. Depo- fore, requiring higher doses for suppression Proveras is an effective interim method (Bertschinger et al., 2001, 2002). Dosing is because it is generally short term and can based on weight of the individual, species be administered by dart, therefore anaesthe- being treated and gender. Typically the tizing the individual is unnecessary. Depend- wolves and African wild dogs require multi- ing on the focal animal and the goal of the ple implants whereas for the fox species, just institution, preferred contraception methods one implant is necessary for suppression vary. (S. M. Boutelle, unpubl. data). Males need From Table 1 it is apparent that a wide higher doses than ,, to suppress spermato- range of Canidae species can be treated. genesis completely and azoospermia may Although historically the MGA implants take up to 6 weeks after treatment or longer were more commonly used, Suprelorins (S. M. Boutelle, unpubl. data). (either formulation) is now recommended The main challenges facing animal man- and gaining in popularity (http://www. agers and veterinarians when treating indivi- stlzoo.org/contraception). Similar to any new duals with Suprelorins are dosing and method, information is still being gathered duration of efficacy. Dosing is based on a and analysed for dosing, efficacy and reversi- variety of parameters but there are also

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London 112 BEARS AND CANIDS

PROGESTINS GnRH AGONISTS SUPRELORINs or MGA IMPLANT DEPO-PROVERAs SUPRELORIN 12s LUPRONs

African wild dog pp p p Lycaon pictus fox pp Alopex lagopus Bat-eared fox pp Otocyon megalotis Black-backed jackal pp Canis mesomelas pp venaticus p Vulpes corsac p Cuon alpinus p Fennec fox pp Vulpes zerda Gray wolf pp p Canis lupus pp Chrysocyon brachyurus Mexican gray wolf pp Canis lupus baileyi pp Canis rufus Singing dog p Canis lupus dingo Spotted pp Crocuta crocuta p hyaena pp Vulpes velox

Table 1. Summary of the canid species known to have been treated with progestins and gonadotropin-releasing hormone agonists: GnRH, gonadotropin-releasing hormone; MGA, melengestrol acetate contraceptive. individual differences. Records from the below but additional studies will be necessary AZA WCC Database suggest two implants to delineate these questions. may sufficiently down-regulate one , but not be a high enough dose for another seemingly Gray wolf and Mexican gray wolf identical ,. The reasons for these differences require further investigation but a few possi- Gray wolves originally inhabited most of the bilities are the individual’s metabolism, social ; however, presently pressures within the group and/or distinct they are only found in the , physiological variations. Duration of efficacy , and some of Eurasia. Packs is also variable for each individual and the generally comprise five to nine individuals same parameters for dosing may also affect with one alpha pair. International Union for the length of time for suppression. More Conservation of Nature (IUCN) has delisted details on dosing for each species are outlined the Gray wolf in the United States to Least

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London REVIEW: CONTRACEPTION CHALLENGES IN CANIDAE 113

Concern (IUCN, 2008). Mexican gray were not sufficiently down-regulated. This wolves are considered to be the rarest sub- may because they were treated during pro- species of Gray wolf and their natural range oestrus, not before, and thus the ,, presum- was central to northern and south- ably ovulated during the stimulation phase. west United States. The United States Fish More information is required in to and Wildlife Service has recently begun re- understand why these particular individuals introduction programmes to establish packs did not respond as well as others that had back in the wild. Mexican gray wolves are successful treatments. considered endangered, and the United States and Mexico are collaborating to further these Maned wolves reintroduction efforts (http://www.fws.gov/ Maned wolves currently are found in both southwest/es/mexicanwolf). Brazil and portions of Peru although histori- Gray wolves and Mexican gray wolves s cally they also were spread across Uruguay have been treated with Suprelorin over and Argentina. In the wild, this species has several breeding seasons in AZA accredited committed < and , pairs that share a territory; institutions located in the United States. Be- however, they remain fairly independent ex- cause these species are highly seasonal it is cept during breeding. Observations from cap- only necessary to treat with the 6 month tive pairs show an increased amount of formulation just before pro-oestrus to ensure interaction and a more active role for the << down-regulation during the breeding season. in . At this time, the Convention If treatment occurs during or after pro-oestrus on International Trade of the ,, will usually ovulate and become of Wild Fauna and Flora (CITES) considers receptive to << (S. M. Boutelle, unpubl. the data deficient for Maned wolves, and data). It is critical to treat before this time in IUCN lists the species as Near Threatened order to prevent ovulation resulting in preg- (IUCN, 2008), although the exact status is nancy or pseudo-pregnancy. By treating be- unknown. fore pro-oestrus this will also ensure < Several Maned wolves in AZA-accredited wolves will likely not have begun spermato- institutions have been monitored after Supre- genesis and, therefore, fertilization will be s lorin treatment and one individual subse- further prevented (Asa et al., 1990). Efficacy quently became pregnant and produced pups, and reversibility have been established in therefore documenting a reversal. No hor- both Gray wolves and Mexican gray wolves. mone monitoring has been conducted on Four < Gray wolves treated (each received these individuals but suppression of oestrous three 4 7 mg implants) before the breeding behaviour is apparent, which is indicative of season were azoospermic during treatment an effective dose. For each treatment, the , but semen production returned the following wolves received two implants each; either season in three of the four <<, demonstrating two 4 7 mg or two 9 4 mg implants depend- reversibility (C. Asa, pers. comm.). The ing on the need for a 6 or 12 month duration. fourth < could not be captured and, therefore, The , on record had pups after three con- semen parameters were not analysed. Female secutive years of treatment (two 4 7 mg im- Gray wolves (n 5 4) were also treated (each plants for each treatment) and conceived received two 4 7 mg implants) and moni- within 1 after the last implant expired. tored for faecal progestin levels. All ,, showed a return to cycling the following Fennec fox breeding season (C. Asa, pers. comm.). These ,, were not in a breeding situation, however, Fennec fox are mostly monogamous and both so no pups were produced. Although efficacy the < and , invest in parental duties. Social and reversibility have been demonstrated groups generally consist of large family there have been instances where ,, were groups of approximately ten individuals. This treated with up to three 4 7 mg implants and species inhabits Central and

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London 114 BEARS AND CANIDS currently CITES has not been able to evaluate cause of fatalities (nine of 15, van Heerden, their status sufficiently, thus they are consid- 1986; 13 of 61, van Heerden et al., 1996). ered data deficient, while IUCN lists the These figures exclude perinatal mortalities. species as Least Concern (IUCN, 2008). Breeding is confined to the alpha , although Data for Suprelorins treatment are also sub-ranking ,, have been known to breed available in the Fennec fox. Eight ,, were (M. Hofmeyr, pers. comm.). Multi-sire breed- involved in a research study in which faecal ing has been observed with sub-ranking << progesterone concentration hormones were only mating in the latter stages of oestrus. monitored to track suppression of ovarian Parentage analysis has shown up to three sires activity following the insertion of one 3 mg for a single litter (Mouiex, 2006). Male wild Suprelorins implant (Bertschinger et al., dogs produce sperm throughout the year, 2001). Following treatment, as evidenced by although there is proof of seasonal variation low concentrations, ovarian ac- in semen quality (No¨thling et al., 2002). The tivity was suppressed in five individuals; reproductive drive of this species appears to however, the duration of suppression varied be exceptional and this may explain why between individuals. Three of the five indivi- reproductive control is more difficult than in duals had detectable progesterone levels, in- species with similar social systems. The fact dicating a return to cycling, within 1 5 years that spermatogenesis is a continuous, year- post implant placement. Monitoring did not round process, should be considered if << are continue for the last two suppressed indivi- to be contracepted. Down-regulation should duals and return to cycling is unknown at this take place a minimum of 8 weeks before the time. breeding season. Treatment of ,, for contra- ception should also be carried out before the breeding season before pro-oestrus com- African wild dogs mences. African wild dogs live in packs of seven to 28 To the authors’ knowledge, the use of adults and yearlings in a structured hierarchy same-sex groups to control breeding in Afri- with the alpha , and alpha < as the dominant can wild dogs has only been practiced with pair (Creel & Creel, 2002). Currently the << at The Ann van Dyk Cheetah Centre. IUCN (2008) designates this species as En- Group sizes have varied from two to six dogs, dangered and significant efforts are under some of which have been together for up to way to ensure their survival. African wild 5 years. Enclosure size appears to have an dog pairs are monoestrous seasonal breeders influence on the incidence of aggression. and in South Africa oestrus and mating are Where there is sufficient space for avoidance observed during late summer, with pups born (42 ha) serious fighting is not observed. In February–March. At The Ann van Dyk Chee- smaller camps, aggression may be common, tah Centre a secondary breeding period may especially during the main breeding season occur during the spring months in packs that but also during the secondary breeding sea- have not bred during late summer (H. J. son (H. J. Bertschinger, unpubl. data). Ac- Bertschinger, unpubl. data). The approach of cording to van Heerden et al. (1996) the the breeding season is associated with in- housing of ,, in same-sex groups is more creased aggression within the pack, which is likely to lead to mortalities as a result of likely related to subordinate animals trying to fighting during the breeding season and increase their ranking within the group. At- should, therefore, not be practiced. tacks on individuals are often severe and Once again at The Ann van Dyk Cheetah fatalities can occur. This may be worse in Centre, salpingectomy of two ,, as a means captive situations where avoidance by sub- of contraception in a group of litter mates [3.2 ordinate dogs is less feasible. Two studies on (<.,)] has worked extremely well. Surgery captive dogs in South Africa revealed trauma was carried out in 2003 with no problems as a result of fighting to be the most common having been observed since then. Signs of

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London REVIEW: CONTRACEPTION CHALLENGES IN CANIDAE 115 oestrus have been observed in both ,, each trations revealed that five ,, ovulated at year. various intervals following treatment but only African wild dogs appear to be extremely two became pregnant (one after 4 weeks and sensitive to the side effects of progestins the other after 3 months), possibly as a result (J. van Heerden, pers. comm.) as well as of an inadequate dose. Anoestrus was main- repeated pseudo pregnancies (H. J. Bertschin- tained in the other six ,, and reversal could ger, unpubl. data). Two ,, given a single be demonstrated in five of them that success- treatment of 400 mg proligestone (Delvoster- fully produced normal-sized litters after 7, 11, on) to postpone oestrus both developed fatal 12, 13 and 16 months. The two ,, (out of the pyometra within a few months of treatment five that ovulated at various intervals follow- (J. van Heerden, pers. comm.). As with other ing treatment) that fell pregnant after treat- carnivore species, both endogenous and syn- ment produced a second litter 14 and thetic progesterone may increase the risk for 15 months after the implants (Bertschinger uterine pathology in canids (Asa & Porton, et al., 2002). Because the results with the 2005; Munson et al., 2005; Moresco et al., early 6 mg deslorelin implants were more 2009). Therefore, progestin-based contracep- reliable in << than ,,, management practices tion is not recommended (http://www. at The Ann van Dyk Cheetah Centre changed stlzoo.org/contraception). Salpingectomy of to targeting largely << for contraception. The ,, and vasectomy of << are also not recom- treatment remained successful as long as it mended as pseudo-pregnancies may result was applied at least 2 months before the when repeated non-fertile cycles occur. As a breeding season (H. J. Bertschinger, unpubl. result, it seems unwise to use any formulation data). of progestins to control reproduction in , Initial studies with deslorelin implants African wild dogs. made available in the late 1990s (3 and 6 mg African wild dogs have been treated with implants) in six << yielded promising results Suprelorins for both contraception and ag- (Bertschinger et al., 2002). Males examined gression management in North American at different intervals from one to as long as zoos. Anecdotal information suggests that 14 months after treatment had baseline testos- these individuals are highly variable in their terone levels. Male M141 (Fig. 1) was placed suppression and duration of efficacy. There with three ,, at the time of the first treatment. are limited data thus far for reversibility. So One , that came on heat 3 weeks later pro- far, three individuals have reportedly had duced a litter, likely because < was not yet offspring after one treatment (4 7 mg formu- azoospermic after treatment. The other two lation for each) with no associated problems, ,, came on heat 6 weeks after treatment of according to the AZA WCC database. The the < and no pregnancy was observed. Where possible application for Suprelorins in Afri- measured, testicular volume (data not shown) can wild dogs for decreasing aggression was also reduced consistently. Positive proof among bachelor groups and management of reversal of contraception was provided in practice is especially helpful for institutions two of five African wild dogs. One < mated housing multiple social groups, which need successfully 16 months after deslorelin treat- flexibility for exhibits. ment and the other had good semen quality In South Africa, at least 19 < dogs (15 and normal plasma testosterone concentra- treated once; two treated twice; two on three tions 12 months after deslorelin administra- separate occasions) and 18 , dogs have been tion; follow-up information is not available treated with deslorelin (Suprelorins). Details for the others. Since the introduction of the were available for 11 of the 18 ,,, which new Suprelorins implants in 2005 the results were initially treated with 6 mg deslorelin have been less consistent. Although testicular implants during the 1999–2000 period, while volume could be reduced in some dogs, most in anoestrus and housed with << (Bertschin- treated << have remained fertile. Figure 2 ger et al., 2002). Serum progesterone concen- shows a < (M176) that was initially treated

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London 116 BEARS AND CANIDS

16 M141: 6 mg 14 12

10 6 mg testosterone 8 6 4 testosterone nmol/litre 2 0 0 13914 months from 1st treatment

Fig. 1. Successful down-regulation of testosterone production in an African wild dog Lycaon pictus < (M141) 1, 3, 9 and 14 months after treatment with a 6 mg deslorelin implant. indicates time of deslorelin implant.

M176: 6 mg, 6 mg, 4.7 mg

testosterone test volume 16 16000

14 14000

12 6 mg 6 mg 12000 3

10 10000 4.7 mg 8 8000

6 6000

4 4000 testicular volume mm testosterone nmol /litre 2 2000

0 0 0 1218242730444856 months from 1st treatment

Fig. 2. African wild dog Lycaon pictus (M176) treated before two consecutive breeding seasons with single 6 mg deslorelin implants. Twelve months following first implant testosterone was within the normal range. Six months after the second implant testosterone concentrations were baseline and the mean testicular volume (test volume) small. Reversal of both variables can be seen 6 and 9 months later. After 48 months, a single Suprelorins (4 7 mg) implant showed a partial response in both variables 8 months later. successfully with 6 mg implants in two con- the second implant. During the next 9 months secutive years, 3–4 months before the breed- both testicular volume and serum testosterone ing season. The , that was with him during concentration increased demonstrating the both seasons following implantation of the < reversal process. Finally this < was treated did not fall pregnant. Figure 2 also shows that with a Suprelorins 4 7 mg implant 48 12 months after the first implant, testosterone months after the initial treatment but this only concentrations were within the normal range resulted in part down-regulation 8 months and were down-regulated 6 months after later. Figure 3 shows down-regulation of

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London REVIEW: CONTRACEPTION CHALLENGES IN CANIDAE 117

M378: 4.7 mg testosterone test volume 16 16000

14 14000 3 12 4.7 mg 12000 10 10000

8 8000

6 6000

4 4000 testicular volume mm testosterone nmol/litre

2 2000

0 0 –4 0 4 months from 1st treatment

Fig. 3. Down-regulation of spermatogenesis as reflected in testicular volume (test volume) and partial down- regulation of testosterone production in an African wild dog Lycaon pictus < (M378) 4 months after treatment with a single dose of Suprelorins (4 7 mg). Arrow indicates time of Suprelorins implant. mean testicular volume in a < (M378) treated apparent differences between the original with a single 4 7 mg implant but only partial implants and the new formulations are un- the down-regulation of testosterone produc- known. It is likely that further trials are tion that we would expect (i.e. to have necessary for these newer implants to reached baseline concentrations after 4 determine exact dosing protocols for exotic months) occurred. Other << treated with the species. same dose showed no response for either The choice of which gender to target when variable. It seemed logical, therefore, that a it comes to the African wild dog may be double implant of Suprelorins should be important from a health and welfare point of sufficient to achieve contraception. However, view. In ,, the use of progestins of any kind as can be seen from the two << in Fig. 4, this and duration should not be considered be- was not the case. Four months after treatment cause of the risk of the cystic endometrial < M325 (Fig. 4a) showed no significant hyperplasia–pyometra complex (J. van Heer- reduction in testicular volume and testo- den, pers. comm.). The results achieved in sterone concentration remained within the << with the original 6 mg deslorelin implants normal range for African wild dogs were good and no pregnancies occurred in (Bertschinger et al., 2002). Male M380 (Fig. mixed groups when treated before pro-oes- 4b) showed good down-regulation of testicu- trus. Females, on the other hand, had a failure lar volume and a partial down-regulation of rate of around 13%. Presuming the protocol testosterone concentration was observed. It for the new Suprelorins 4 7or9 4mg would seem that the 4 7 mg Suprelorins implants can be adapted to achieve the same implants result in systemic concentrations good results in < dogs once again, the results that are close to the threshold required to reported above may suggest targeting <<. down-regulate < African wild dogs. It would Recent evidence, however, may persuade appear that some individuals respond, some managers to reconsider this decision. During respond partially (i.e. remaining fertile) and a the last 2 years there has been a sudden third group does not respond at all to such increase in the prevalence of cystic endome- treatments. The precise reason/s for these trial hyperplasia–pyometra complex at The

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M325: 2 x 4.7 mg testosterone test volume

16 a 16000 14 14000 3 12 12000 10 2x4.7 mg 10000 8 8000 6 6000 4 4000 2 2000 testicular volume mm 0 0 –15 –4 0 4 months from 1st treatment

M380: 2 x 4.7 mg testosterone test volume 16 16000

b 3 14 14000 12 12000 2x4.7 mg 10 10000 8 8000 6 6000 4 4000 2 2000 testicular volume mm testosterone nmol/litre0 testosterone nmol/litre 0 –4 0 4 months from 1st treatment

Fig. 4. Two African wild dog Lycaon pictus << treated with double Suprelorins implants (2 4 7 mg). Arrows indicate time of Suprelorins implant; (a) M325 yielded a negative response for both serum testosterone concentration and mean testicular volume (test volume) after 4 months; (b) M380 showed reduction in mean testicular volume and a partial response for testosterone concentration.

Ann van Dyk Cheetah Centre. Instead of Without responsible management zoological sporadic cases (o1 year 1) six cases, one of institutions may be faced with hard decisions, which occurred in a 4 year-old ,, were re- such as how to control surplus animals. corded (the other ,, were older). Concerns Reversible contraception methods may also are increasing that repeated non-pregnant be the best option for many individuals with- dioestrus (pseudo-pregnancies), as a result of in the population, which currently are not < contraception, may be the cause of the essential for breeding but could be called on increased prevalence. This is well established in the future. For the species mentioned in in the Domestic dog (Dow, 1957). Although this paper, all play a critical role in the the evidence is only anecdotal (H. J. ecosystem and, thus, ensuring their survival Bertschinger, unpubl. data), it may be better is very important. Many options for control- to target the , for contraception by inducing ling reproduction are available, such as anoestrus. separating genders, surgical sterilization, immunological methods or hormonal contra- SUMMARY ception. However, for these highly social Canidae it is desirable to keep family groups In conclusion, reversible contraception is an together as a more natural management essential tool for reproductive management. practice. Hormonal contraception would,

Int. Zoo Yb. (2010) 44: 109–120. c 2010 The Authors. Journal compilation c 2010 The Zoological Society of London REVIEW: CONTRACEPTION CHALLENGES IN CANIDAE 119 therefore, be a good option to sustain these BERTSCHINGER, H. J., JAGO, M., NO¨ THLING,J.O.& HUMAN, groups and manage the breeding populations. A. (2006): Repeated use of the GnRH analogue deslor- For animal managers and veterinarians it is elin to down-regulate reproduction in male cheetahs (Acinonyx jubatus). Theriogenology 66: 1762–1767. essential to keep the welfare of the animal, BERTSCHINGER, H. J., DE BARROS VAZ GUIMARA˜ ES, M. A., the overall goals for each species and any TRIGG,T.E.& HUMAN, A. (2008): The use of deslorelin institutional constraints in mind when choos- implants for the long-term contraception of lionesses and ing which method is best. Growing evidence . Wildlife Research 35: 525–530.. ´ ´ suggests that treating , Canidae with Supre- BOUE, F., ROUTE, N., FARRE,G.& VERDIER, Y. (2002): s s Challenges and strategy for the development of an lorin or Suprelorin12 may be the best immunocontraceptive vaccine specific to the red fox option in order to avoid uterine pathology (Vulpes vulpes). In Fertility control in wildlife. Proceed- after exposure to endogenous progesterone ings of the fifth international symposium of fertility following repeated non-fertile cycles. As out- control in wildlife, Skukuza Camp, Kruger National Park, South Africa, 19–22 August. Reproduction lined above, African wild dogs appear to be 60(suppl.): 45–46. Kirkpatrick, J. F., Lasley, B. L., Allen, specifically at risk and, therefore, it is essen- W. R. & Doberska, C. (Eds). Cambridge: Society for tial Suprelorins dosing is further studied for Reproduction and Fertility. this species. For the most up to date recom- CREEL,S.& CREEL, N. M. (Eds). (2002): The African wild dog: behaviour and ecology. Princeton, NJ: Princeton mendations visit the AZA WCC webpages University Press. 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