This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier’s archiving and manuscript policies are encouraged to visit: http://www.elsevier.com/copyright Author's personal copy Journal of Reproductive Immunology 83 (2009) 151–157 Contents lists available at ScienceDirect Journal of Reproductive Immunology journal homepage: www.elsevier.com/locate/jreprimm The practical side of immunocontraception: zona proteins and wildlife J.F. Kirkpatrick a,∗, A. Rowan b, N. Lamberski c, R. Wallace d, K. Frank a, R. Lyda a a The Science and Conservation Center, ZooMontana, Billings, MT 59106, USA b The Humane Society of the United States, Gaithersburg, MD, USA c San Diego Wild Animal Park, Escondido, CA, USA d Milwaukee County Zoo, Milwaukee, WI, USA article info abstract Article history: With shrinking habitat, the humane control of certain wildlife populations is relevant. The Received 31 December 2008 contraceptive vaccine based on native porcine zona pellucida (PZP) has been applied to Received in revised form 16 June 2009 various wildlife populations for 20 years. Prominent efforts include wild horses, urban Accepted 16 June 2009 deer, zoo animals and African elephants, among others. This approach has been successful in managing entire populations and to date, no significant debilitating short- or long-term Keywords: health effects have been documented. Immunocontraception © 2009 Elsevier Ireland Ltd. All rights reserved. Population control Wildlife Porcine zona pellucida 1. Introduction function (Skinner et al., 1984; Mahi-Brown et al., 1985; Dunbar et al., 1989; Jones et al., 1992). These studies About 37 years back, it was demonstrated for the first suggest that PZP-based immunocontraceptive vaccines, at time that antibodies against zona pellucida (ZP) may be least in some species, may curtail fertility either by inter- possible for inhibition of fertility (Ownby and Shivers, fering in the normal physiology of ovaries or by blocking 1972). Since then, several groups have investigated the fertility. This coupled with the variability in contraceptive potential of ZP-based immunocontraceptive vaccines in a efficacy and time taken for the recovery of fertility after variety of animal models (Kirkpatrick et al., 1996; Gupta et immunization led to abandonment of PZP-induced human al., 2004). Porcine zona pellucida (PZP) became the antigen contraception. of choice due to easy accessibility of porcine ovaries from Significant population problems, however, exist in abattoir and observations that antibodies against PZP react species other than humans. Certain wildlife populations with zona from various species and inhibit in vitro human may not for societal and other reasons, lend themselves to fertilization (Sacco, 1977). Indeed, active immunization lethal management approaches, and companion animals studies with purified PZP, employing various animal mod- pose a serious dilemma in many countries. Captive ani- els have established the efficacy of such an approach to mal populations in zoological gardens must be regulated control fertility (Skinner et al., 1984; Mahi-Brown et al., because of limited space. Thus in 1989 PZP was tested in 1985; Sacco et al., 1986). However, interest and invest- a new role—namely, control of wildlife fertility. Happily ment in zona-related research for human fertility control this use has proven effective, safe and practical. The first declined due to the observation in some animal models species to be targeted was the horse, where PZP was shown that infertility is invariably associated with ovarian dys- to be effective in inhibiting fertility (Liu et al., 1989). PZP was then shown to be effective in free-ranging wild horses and burros (Kirkpatrick et al., 1990; Turner et al., 1996), ∗ Corresponding author. Tel.: +1 406 652 9718; fax: +1 406 652 9733. captive and free-ranging white-tailed deer (Turner et al., E-mail address: [email protected] (J.F. Kirkpatrick). 1992; McShea et al., 1997), captive exotic species in zoos 0165-0378/$ – see front matter © 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jri.2009.06.257 Author's personal copy 152 J.F. Kirkpatrick et al. / Journal of Reproductive Immunology 83 (2009) 151–157 Table 1 Species in which PZP contraception has been successful. Ungulata Perissodactyla Horse (Equus caballus) Plains Zebra (E. burchelli) Donkey (E. asinus) Mountain Zebra (E. zebra) Przewalski’s Horse (E. przewalskii) Black Rhinoceros (Diceros bicornus) Grevy’s Zebra (E. grevyi) Tapir (Tapirus indicus) Artiodactyla Addax (Addax nasomaculatus) Gerenuk (Litocranius walleri) Antelope, Roan (Hippotragus equinus) Giraffe (Giraffa camelopardalis) Antelope, Sable (Hippotragus niger) Goat, Mountain (Oreamnos americanus) Banteng, Javan (Bos javanicus) Goat, Domestic (Capra capra) Bison (Bison bison) Hippopotamus (Hippopotamus amphibious) Blackbuck (Antelope cervicapra) Ibex (Capra ibex) Bongo (Tauurotragus euryceros) Impala (Aepyceros melampus) Camel, Dromedary (Camelus dromedarius) Kudu (Tauurotragus strepiceros) Camel, Bactrian (Camelus bactrianus) Llama (Lama glama) Caribou (Rangifer tarandus) Markor (Capra falconeri) Chamois (Rupicaapra rupicapra) Moose (Alces alces) Cow, Domestic (Bos primigenius [Taurus]) Musk Ox (Ovibus moschatus) Deer, White-tailed (Odocoileus virginianus) Nyala (Tauurotragus angasi) Deer, Mule (Odocoileus hemionus) Oryx, Sciimitar (Oryx dammah) Deer, Axis (Cervus axis) Pronghorn, N. A. (Antilocapra americana) Deer, Sika (Cervus nippon manchuriensis) Pudu, Southern (Pudu pudu) Deer, Sika (Cervis nippon taioanus) Serow, Mainland (Capricornus sumatrensis) Deer, Fallow (Cervus dama) Sheep, Big Horn (Ovis canadensis) Deer, Eld’s (Cervus eldi) Sheep, Dall (Ovis dalli) Deer, Pere David’s (Elaphurus davidiensis) Sheep, Mouflon (Ovis musimon) Deer, Muntjac (Muntiacus reevesi) Tahr, Himalayan (Hemitragus jemlahicus) Deer, Sambar (Cervus unicolor) Wapiti, North American (Cervus elaphus) Dik Dik, Kirk’s (Madoqua kirkii) Wapiti, Roosevelt (Cervus e. roosevelti) Duiker, Red Flanked (Cephalophus rufilatus) Waterbuck, Defassa (Kobus ellipsiprymnus) Duiker, Yellow-backed (C. sylvicultor) Water Buffalo, Asian (Bubalis arnee) Edmi (Gazella cuvieri) Wisent, Lowland (Bison bonasus) Eland (Taurotragus oryx) Yak (Bos mutus) Gazelle, Thomson’s (Gazella thomsoni) Elephantidae and Carnivora Elephantidae African elephant (Loxodonta africana) Carnivora Bear, American Black (Ursus americanus) Bear, Asian Black (Selenarctos thibetanus) Bear, Sun (Helarctos malayanus) Sea Lion, California (Zalophus Californian) Bear, Brown (Ursus arctos) (Kirkpatrick et al., 1995), free-ranging wapiti (Garrott et 2. Population management al., 1998), and even free-ranging African elephants (Fayrer- Hosken et al., 2000). PZP has successfully inhibited fertility At least four examples of effective population man- in 80 species of mammalian wildlife, either free-ranging agement with PZP immunocontraception are available. A or captive (Table 1). The wide range of species suggests a population of wild horses (Equus caballus) on Assateague strong evolutionary conservation of the sperm receptor, at Island National Seashore, MD, has been managed since least within family Ungulata. However, there is consider- 1994 with PZP. Initially all mares were given a 100 ␮g able difference in each species’ ability to generate antibody primer dose of PZP followed-up by a booster dose of titers and the duration of the antibody response (Frank et 100 ␮g a year later. All vaccine treatments were delivered al., 2005). remotely, via small 1.0 cc darts. After 3 consecutive years Demonstrating that a contraceptive is effective on a of treatment, animals were withdrawn from contraception physiological level does not however, ensure that it has until they produced a single healthy foal and then placed practical value in the realm of population control. The back on treatment until extinction. There were 175 horses remainder of this paper will examine actual progress in the population. After 14 years of immunocontraception, in population control, safety issues and differences in the population has been reduced to 125, with a goal of 120 response by various species. Unless otherwise noted, the animals (Fig. 1; Kirkpatrick and Turner, 2008). PZP vaccine referenced is native PZP as prepared by the In the case of urban white-tailed deer (Odocoileus vir- general methodology described previously (Dunbar et al., ginianus) inhabiting Fire Island National Seashore, NY, the 1980) at doses of 65–100 ␮g, and administered exclusively fawn production and total population has declined signif- in the hip or gluteal muscles. icantly over the period of time that immunocontraception Author's personal copy J.F. Kirkpatrick et al. / Journal of Reproductive Immunology 83 (2009) 151–157 153 Fig. 1. Population changes of the Assateague Island National Seashore, Maryland, USA wild horse herd over a 38-year period. Contraceptive management began in 1994, as described in the text. Adapted from Kirkpatrick and Turner (2008).