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Suppression of ovarian activity in a captive African Lion Panthera leo after deslorelin treatment

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de B.V. Guimar es (2020). Suppression of ovarian activity in a captive African lion (Panthera leo) after deslorelin treatment. Journal of Threatened Taxa 12(11): Abstract: With the intent to evaluate the efficiency of a contraceptive treatment for cyclic ovarian suppression in African Lionesses Panthera leo using a Gonadotrophin-Releasing Hormone (GnRH) agonist bioimplant, noninvasive fecal steroid assay associated with the observation of the behavioral estrus were employed for a period of 36 months. Five captive adult females, maintained with a vasectomized male, subcutaneously received a 9.4mg deslorelin acetate implant. The treatment initially stimulated behavioral estrus along with ovarian activity, demonstrated by an estrogen increase in two lionesses. A rise in progesterone concentration in two other animals suggested possible treatment-induced ovulation. After the initial period, deslorelin prevented ovarian activity for at least 22 months. Two females exhibited signs of behavioral estrus after 22 and 31 months. A third lioness with an increased estrogen concentration did not exhibit behavioral estrus signs or a consequent progesterone surge until 33 months after implantation, suggesting a possible resumption of ovarian activity. One female did not exhibit any behavioral estrus signs nor a rise in steroid levels after the treatment-induced estrus throughout the entire experiment (36 months). One lioness died after 15 months without exhibiting signs of estrus or an increased progesterone level, however, the estrogen concentration increased 12 months post-implantation, suggesting resumed ovarian activity. The study showed that long-term treatment with a GnRH agonist can be extremely effective as a contraceptive treatment in African lionesses, however, the duration of contraception may vary among individuals and may bear the risk of permanent loss of normal ovarian activity.
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16469
Editor: Rajeshkumar G. Jani, Anand Agricultural University, Anand, India. Date of publicaon: 26 August 2020 (online & print)
Citaon: D.P. de A.F. Braga, C.S. Pizzuo, D.A. Roseneld, P.V. Furtado, C.A. Oliveira, S.H.R. Corra, P.N. Jorge-Neto, & M.A. de B.V. Guimares (2020). Suppression
of ovarian acvity in a capve African lion (Panthera leo) aer deslorelin treatment. Journal of Threatened Taxa 12(11): 16469–16477. hps://doi.org/10.11609/
jo.5803.12.11.16469-16477
Copyright: © Braga et al. 2020. Creave Commons Aribuon 4.0 Internaonal License. JoTT allows unrestricted use, reproducon, and distribuon of this arcle
in any medium by providing adequate credit to the author(s) and the source of publicaon.
Funding: This work was supported by FAPESP (Grant no. 04/14135-6; MABV Guimares).
Compeng interests: The authors declare no compeng interests.
Portuguese abstract and Author contribuon see end of this arcle.
Author details: D P  A F B, DMV, PhD. Head of Research at the Ferlity Medical Group. C S P, DMV, MSc,
PhD, Postdoc. Assistant Professor at School of Veterinary Medicine and Animal Science of University of So Paulo. Chairman of the Animal Welfare Commiee of
CRMV - SP. Member of the Internaonal Environmental Enrichment Conference Commiee and of REPROCON research group. D A R, DMV,
MSc, PhD. Specialist in non-lethal wildlife populaon control methods. P V F, DMV, MSc, PhD. Specialist in charge of the Laboratory of Hormonal
Dosages of School of Veterinary Medicine and Animal Science of University of So Paulo. C A. O, DMV, MSc, PhD, Postdoc. Full Professor at School of
Veterinary Medicine and Animal Science of University of So Paulo. S H R C, DMV, MSc, PhD. Assistant Professor at Federal University of
Mato Grosso (UFMT) and Manager of the Wild Animal Medicine and Research Center of UFMT. P N J-N,DVM, MBA, MSc. Actually, PhD student
(PPGRA-FMVZ / USP) and Technical-Commercial Director of IMV Technologies Brazil. Member of REPROCON research group. M A  B V
G (in memorian), DMV, MSc, PhD. Associate Professor at School of Veterinary Medicine and Animal Science of University of So Paulo.
Acknowledgements: The authors acknowledge the following instuons and persons: Fundao Parque Zoológico de So Paulo; and Professor Marcelo A. de
Barros Vaz Guimares (in memorian) for the friendship and teachings transmied in the reproducon of wild animals.
Journal of Threatened Taxa  www.threatenedtaxa.org  26 August 2020  12(11): 16469–16477
Suppression of ovarian acvity in a capve African Lion Panthera leo
aer deslorelin treatment
Daniela Paes de Almeida Ferreira Braga 1 , Crisane Schilbach Pizzuo 2 , Derek Andrew Roseneld 3 ,
Priscila Viau Furtado 4 , Cláudio A. Oliveira 5 , Sandra Helena Ramiro Corrêa 6 ,
Pedro Nacib Jorge-Neto 7 & Marcelo Alcindo de Barros Vaz Guimares 8
1 Ferlity Medical Group / Av Brigadeiro Luis Antonio, 4545, 01401-002, So Paulo, SP, Brazil.
2, 3, 4, 5, 7, 8 Department of Animal Reproducon, Faculty of Veterinary Medicine and Animal Science, University of So Paulo (USP) / Av.
Prof. Dr. Orlando Marques de Paiva, 87 - Cidade Universitária, So Paulo / SP, 05508-270, Brazil.
6 Faculty of Veterinary Medicine and Animal Science, Federal University of Mato Grosso (UFMT), Av. Fernando Corra da Costa - Coxipó,
Cuiabá - MT, 78060-900, Brazil.
1 dbraga@ferlity.com.br (corresponding author), 2 cspizzuo@yahoo.com.br, 3 dro@usp.br, 4 priviau@usp.br, 5 cadolive@usp.br,
6 correasandrahelena@gmail.com, 7 pepovet@usp.br
Abstract: With the intent to evaluate the eciency of a contracepve treatment for cyclic ovarian suppression in African Lionesses Panthera
leo using a Gonadotrophin-Releasing Hormone (GnRH) agonist bioimplant, noninvasive fecal steroid assay associated with the observaon
of the behavioral estrus were employed for a period of 36 months. Five capve adult females, maintained with a vasectomized male,
subcutaneously received a 9.4mg deslorelin acetate implant. The treatment inially smulated behavioral estrus along with ovarian acvity,
demonstrated by an estrogen increase in two lionesses. A rise in progesterone concentraon in two other animals suggested possible
treatment-induced ovulaon. Aer the inial period, deslorelin prevented ovarian acvity for at least 22 months. Two females exhibited
signs of behavioral estrus aer 22 and 31 months. A third lioness with an increased estrogen concentraon did not exhibit behavioral estrus
signs or a consequent progesterone surge unl 33 months aer implantaon, suggesng a possible resumpon of ovarian acvity. One
female did n ot exh ibit any be havioral estrus signs nor a rise in steroid levels aer the treatme nt-induce d est rus t hroughout the enre
experime nt (36 months). On e lioness died aer 15 mo nths without exhibing signs of estrus or an increased progesterone level, however,
the estrogen concentraon increased 12 months post-implantaon, suggesng resumed ovarian acvity. The study showed that long-term
treatment with a GnRH agonist can be extremely eecve as a contracepve treatment in African lionesses, however, the duraon of
contracepon may vary among individuals and may bear the risk of permanent loss of normal ovarian acvity.
Keywords: African Lion, contracepon, estrus behavior, fecal assay, GnRH agonist.
ISSN 0974-7907 (Online) | ISSN 0974-7893 (Print)
C
#5803 | Received 25 February 2020 | Final received 19 August 2020 | Finally accepted 21 August 2020
DOI: hps://doi.org/10.11609/jo.5803.12.11.16469-16477
PLATINUM
OPEN ACCESS
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477
Suppression of ovarian acvity in a capve African Lion Braga et al.
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INTRODUCTION
The reproducon of wild animals in capvity is an
important tool for ex situ conservaon of endangered
species (Jorge Neto et al. 2018b). Some species such
as the African Lion Panthera leo, however, can adapt to
capvity, and thus, are capable of reproducing in such
an environment. The abundant reproducon of large
carnivores is associated with low adult mortality and
increased longevity in capvity. This creates a number
of complicaons as the physical space and nancial
resources available for their maintenance is limited
(Woodroe & Frank 2005).
The objecve of the present study was to use the
noninvasive fecal steroid assay associated with behavioral
estrus to evaluate the eciency of chronic treatments
with the Gonadotrophin-Releasing Hormone (GnRH)
agonist bioimplants to suppress cyclic ovarian acvity in
African Lionesses.
MATERIALS AND METHODS
Experimental Design
Five adult African Lionesses (L1, L2, L3, L4 and L5)
were maintained in capvity with a vasectomized male
at the Zoological Park of So Paulo. All females had at
least one conrmed pregnancy with a live birth, and
none of them had been previously submied to any
kind of contracepve management, except for physical
separaon from male lions and me with vasectomized
males. L1 (13 years old), L2 (6 y/o) and L4 (6 y/o) were
born in the So Paulo Zoo, while L3 (7 y/o) and L5 (7 y/o)
came from another capve facility when they were six
months old.
The ve lionesses received a 9.4mg deslorelin acetate
implant subcutaneously. The eciency of the implant as
a contracepve was evaluated non-invasively using a fecal
steroid assay and through observaon of the behavioral
estrus. The study was approved by the University’s Ethics
Commiee for Use of Animals in Research (CEUAVET-
USP).
Gonadotrophin-Releasing Hormone Agonist Bioimplant
Formulaon and Implantaon
The GnRH agonist bioimplants used in the present
experiments were supplied by Peptech Animal Health
Pty Limited, Australia (Suprelorin 9.4 mg; No. 978;
Batch DR023). Each implant contained 9.4mg of GnRH
agonist deslorelin acetate (C64H83N17O12). Implants were
placed subcutaneously under asepc condions using a
commercial implanng device.
Sample Collecon, Hormone Extracon, and Dosage
During the experiment, two fecal samples were
collected twice weekly, sealed in plasc bags, labeled with
the individual’s name/date, and stored at -20°C. From 45
days before to 36 months aer implant, fecal aliquots
were extracted to quanfy estrogen and progestogen
metabolites. Fecal hormone metabolites were extracted
from the samples, as previously described (Brown et
al. 1994). Briey, each fecal sample was lyophilized,
pulverized, and 0.18–0.2 g of dry fecal powder was boiled
in 5mL of 90% ethanol for 20min. During boiling, 100%
ethanol was added as needed, to maintain approximate
pre-boil volumes.
Aer centrifugaon (500g, 20min.), the supernatant
was recovered, and the pellet re-suspended in 5mL of
90% ethanol, vortexed for 30 sec, and re-centrifuged
(500g, 15min.). The rst and second supernatants were
combined, air dried, and reconstuted in 1mL methanol.
Methanol extracts were vortexed briey and placed in a
sonicator for 15min. Each extract was diluted 1:10 in a
steroid diluon buer and stored in polypropylene tubes
at -20°C unl further use.
Subsequently, each sample extract was assayed for
estradiol and progesterone metabolites following RIA.
Estradiol Coat-a-Count RIA kits (Diagnosc Products, Los
Angeles, CA, USA) were used to measure the estradiol
metabolites, while Progesterone DSL-3900 RIA kits
(Diagnosc System Laboratories Inc., Webster, USA) were
used to measure the progesterone metabolites. Samples
were analyzed in duplicate, and those with a coecient
variaon of more than 15% were either re-analyzed (if
there was enough sample volume for re-analysis) or
discarded.
Estrus Behavior Observaon
Animals were observed for 30 min periods twice
each day (during the morning and the aernoon), three
mes a week. The following estrus behavioral paerns
were recorded (Schaller 1972): vocalizaon, restlessness,
increased frequency and intensity of rolling, lordosis,
male aracon, mang acceptance, and copulaon.
RESULTS
Before implant placements, all animals had normal
ovarian acvity, as conrmed by fecal hormone
metabolites dosages (gs. 1–5) and behavioral estrus
signs, such as vocalizaon, restlessness, increased
Suppression of ovarian acvity in a capve African Lion Braga et al.
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477 16471
JTT
frequency and intensity of rolling, lordosis, male aracon,
mang acceptance, and copulaon. The average estrus
length was 5.8 ± 2.2 days. Treatment with deslorelin
inially smulated a behavioral estrus along with ovarian
acvity, as demonstrated by increases in the estrogen
concentraon in two lionesses (L1 and L3, Figs. 1 and 3).
We also noted a rise in progesterone co ncent raon in two
other females (L2 and L5, Figs. 2 and 5), which suggests
possible treatment-induced ovulaon (Table 1). Aer this
period, the GnRH agonist prevented ovarian acvity for at
least 22 months.
Two li ones ses exh ibit ed behavi oral estr us sig ns 22
and 31 months aer implantaon, respecvely (L2
and L3, Figs. 2 and 3, respecvely). In a third lioness
(L4, Fig. 4), behavioral estrus signs and increases in
estrogen concentraon, as well as a consequent surge in
progesterone level was noted 33 months aer implant
use. The lioness L5 (Fig. 5) did not exhibit any signs of
behavioral estrus. Moreover, she only experienced
a rise in female sex steroids levels (estrogen and
progesterone) aer the treatment-induced estrus the
end of the experiment (36 months). The lioness L1 (Fig.
1) died 15 months aer experiment iniaon, without
demonstrang any estrus signs, nor a rise in progesterone
level, however, her estrogen concentraon increased 12
months aer the placed implant (Table 1).
Figure 1. Fecal steroid metabolites prole of the lioness L1 (Panthera leo). Blue arrowdate of Implant placement  Black arrowdate of
death  Red arrowobservaon of estrous behavior.
Table 1. Rise in fecal steroids concentraon and/or estrus behavior shortly aer implant placements, and period of contracepon in African
lions treated long-term with GnRH agonist (deslorelin).
Lioness Estrus behavior
shortly aer implantaon
Rise in fecal progesterone
shortly aer implantaon
Rise in fecal estrogen
aer downregulaon
Estrus behavior aer
downregulaon
Rise in fecal progesterone
aer downregulaon
L1 Yes No 12 months Not observed* Not observed *
L2 No Yes No 22 months Not observed**
L Yes No No 31 months Not observed**
L4 No No No 33 months 33 months
L5 No Yes No Not observed** Not observed**
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477
Suppression of ovarian acvity in a capve African Lion Braga et al.
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Figure 2. Fecal steroid metabolites prole of the lioness L2 (Panthera leo). Blue arrowdate of implant placement  red arrowobserved
estrous behavior.
Figure . Fecal steroid metabolites prole of the lioness L (Panthera leo). Blue arrowdate of implant placement red arrowobserved
estrous behavior.
Suppression of ovarian acvity in a capve African Lion Braga et al.
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Figure 5. Fecal steroid metabolites prole of the lioness L5 (Panthera leo). Blue arrowdate of implant placement  red arrowobservaon
of estrous behavior.
Figure 4. Fecal steroid metabolites prole of the lioness L4 (Panthera leo). Blue arrowdate of implant placement  red arrowobservaon
of estrous behavior.
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477
Suppression of ovarian acvity in a capve African Lion Braga et al.
16474
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DISCUSSION
In the face of the large loss of habitat due to human
encroachment and fragmentaon, some species become
overabundant through human ineptude. Indeed,
humans oen aempt to create condions that favor
the proliferaon of one species over their competors.
Protected parks and reserves provide animals with an
environment that is abundant in resources and predator-
free, condions that allow for unchecked reproducon.
As a result, endangered species undergo a localized
populaon explosion that can have detrimental eects on
the ora and fauna of the reserve, pung other species at
risk; thus, aecng the ecosystem in the same manner as
do invasive species (Grandy & Rutberg 2002; Jewgenow
et al. 2006).
Wildlife populaon control by means of contracepon
has become extremely important, especially for a
number of wild carnivores. Populaon management and
alternave noninvasive contracepve methods have been
studied extensively over the last two decades (Roseneld
2016). Whereas ovariohysterectomy or ovariectomy
alone has been the method of choice for most domesc
cats (Munson 2006), for reproducve management of
threatened or endangered species like the African Lion, a
reversible method is desired. While lions can reach high
densies inside reserves (Packer et al. 2013), they tend to
fare poorly outside protected areas, where they are oen
the rst large carnivore species to disappear (Woodroe
2001).
The GnRH analog deslorelin, a long-acng
biocompable subcutaneous implant that suppresses
specic pituitary funcons, has been recommended
as reversible contracepon (D’Occhio et al. 2002). The
increased release of GnRH into the portal vessels which
connect the hypophysis to the pituitary gland results in
an increased secreon of the follicle smulang hormone
(FSH) and luteinizing hormone (LH), which, in turn,
regulate gonadal funcons (Conn & Crowley 1994). With
connuous exposure to high concentraons of GnRH, the
number of cell surface receptors at the poron of the
adenohypophysis – responsible for FSH/LH synthesis and
releasegradually decreases (Melson et al. 1986) with
a concomitant desensibilizaon eect of gonadotroph
cells on GnRH (D’Occhio & Kinder 1995). By this type of
mechanism, known as receptor down-regulaon, chronic
treatment with a GnRH agonist prevents the pulsale
release of FSH, as well as LH (Gong et al. 1995) and the
pre-ovulatory surge of LH secreon (D’Occhio & Kinder
1995).
The absence of surge-releases of LH in females
treated with a GnRH agonist have led to studies being
conducted on the potenal long-acng contracepve
eects of the GnRH agonist bioimplant by prevenng
follicular development and ovulaon, and consequently,
pregnancies (D’Occhio & Kinder 1995). In addion,
the development of a noninvasive fecal steroid assay
for assessing the ovarian funcon of felid species in
combinaon with behavioral studies makes it possible
to systemacally study various aspects of reproducon
(Brown et al. 1994, 2001; Graham et al. 2006). Therefore,
the goal of the present study is to use the noninvasive
fecal steroid assay associated with behavioral estrus to
evaluate the eciency of chronic treatments with the
GnRH agonist bioimplants to suppress cyclic ovarian
acvity in African lionesses.
The inhibitory eects of ovarian acvies, such as
the arrest of ovulaon caused by desensibilizaon to
endogenous GnRH, provide opportunies to evaluate a
GnRH agonist bioimplant as a potenal anferlity agent
in mammals. In the present experiment, seven lionesses
were implanted with a 9.4 mg deslorelin to monitor
ovarian funcon for 36 months. Fecal steroid assay
and estrus behavioral observaon were the monitoring
methods used. Our ndings suggest that the GnRH agonist
deslorelin suppresses ovarian acvity in African lionesses
for prolonged periods of me. In fact, no behavioral estrus
was noted unl 22 months post-implantaon. In the
22nd, 31st, and 33rd month, behavioral estrus was noted in
three of the lionesses, while the fourth lioness exhibited
increased estrogen concentraons and a consequent
surge in progesterone level that corresponded to the
resumpon of ovarian acvity, including ovulaon, in
addion to behavioral estrus.
One lioness died 15 months aer the beginning of
the experiment without demonstrang any estrus signs
nor a rise in progesterone level. On the other hand, the
estrogen concentraon increased 12 months aer the
implantaon, indicang that the ovarian acvity may have
re-started. Surprisingly, in a single female, neither estrus
behavior nor a rise in fecal progesterone concentraon
was noted up to the end of the experiment.
Var iou s beh avi oral a cvi es that cha rac ter ize es tru s i n
lions appear to be common in several feline species, such
as the domesc cat (Graham et al. 2000; Pelican et al.
2005), Jaguar (Wildt et al. 1979; Jorge-Neto et al. 2018a),
Siberian Tiger (Seal et al. 1987), Snow Leopard (Schmidt
et al. 1993), and Cheetah (Wielebnowski & Brown 1998),
possibly serving as indicators of physiological estrus
in these animals (Umapathy et al. 2007). It, however,
remains unclear why behavioral estrus was observed in
two of the lionesses without a rise in fecal estrogen and
Suppression of ovarian acvity in a capve African Lion Braga et al.
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477 16475
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progesterone metabolites concentraon. Ovulaon in
Panthera genus species is triggered by copulaon or
sensorial smulaon (Jorge-Neto et al. 2020). Therefore,
the lack of ovulaon observed during this study may
demonstrate a estrus detecon failure or a compromised
ovarian funcon. It could also be hypothesized that,
in these cases, ovarian acvity may have re-started
and estradiol concentraon increased, resulng in the
smulaon of behavioral estrus, although, not enough to
trigger the cascade of events to reach ovulaon.
The fact that neither estrus behavior nor a rise in
fecal progesterone concentraon was noted in one of the
lionesses up to the end of the experiment raises concern.
For contracepon to be successful for populaon control,
especially in endangered animals, it must not only be
safe, eecve, and long-acng but also reversible (Castle
& Dean 1996).
To d at e , de s lo r el i n h as b e en u s ed i n c ap  ve - h el d
wild felines, such as cheetahs (Bertschinger et al. 2001),
leopards (Bertschinger et al. 2002) and lions (Bertschinger
et al. 2008), without showing any adverse eects.
Conversely, in domesc cats, a 6mg implant has been
shown to suppress ovarian follicular acvity for between
four and 14 months, however, unl the end of the study
period, eight out of ten cats did not fully return to normal
ovarian cyclicity (Munson et al. 2001). Moreover, dosages
of 12 or 15 mg deslorelin induced contracepve eects
for 12–18 months (Bertschinger et al. 2002). The implant
used in this study (9.4mg) has a matrix without sodium
acetate anhydrous, that allows slow liberaon of the
deslorelin, maintaining contracepve eects for much
longer periods, making it impossible to compare the
eecveness of this dosage in relaon to the duraon
of previous products. It has been reported that the
eecveness duraon of Suprelorin in wild felids is, on
average, twice that prescribed by the manufacturer
in dogs, which means that the 9.4mg implant with a
minimum eecveness of 12 months is generally eecve
for approximately 24 months (Asa et al. 2012). Our
ndings show a ceasing of ovarian acvity of 28.67 ± 5.86
months, which corroborates those found by Bertschinger
et al. (2008), in which implants were eecvely in
lionesses for a period of ~30 months or longer. The
reversal me (or duraon of ecacy) is variable between
species and individuals, probably due to the singularity
in the metabolism of deslorelin or the ability to recover
from down-regulaon (Asa et al. 2012). The ndings
suggest that long-term treatment with deslorelin may
have variability regarding the duraon of contracepon
among individuals due to several factors, including drug/
matrix used; genec and/or environmental inuences.
The disadvantage of using Suprelorin is the inability to
safely predict the duraon of eecveness and the return
of ovarian acvity, being a problem when there is interest
in using these females in conservaon programs.
An extensive study using 140 implants (Suprelorin)
on 14 species of wild felids, including 59 lionesses, was
conducted by the North American Associaon of Zoos
and Aquariums (AZA) and showed no side eects of
deslorelin treatment (Asa et al. 2012). Bertschinger et
al. (2008) used deslorelin treatment in 23 capve and 40
free-ranging lionesses (P. l e o ) and four capve gers (P.
gris) in South Africa and did not observe any side eects
in any females, including some treated four or ve mes
for 5–8 years period. In domesc cat females the use
of Suprelorin appears to be a convenient, ecient and
safe contracepon method, demonstrang female ferle
mang aer approximately two years post-treatment
and no side eects (Fontaine 2015).
Prior to the occurrence of a GnRH agonist anferlity
eect, there is an acute phase (D’Occhio et al. 2002;
Roseneld 2016) in which the secreon of LH and FSH
increase sharply (Gong et al. 1995, 1996), leading to a
corresponding estrus response (Wright et al. 2001). In
the present study, shortly aer placing the implant, two
lionesses exhibited behavioral estrus, and an upsurge
of ovarian acvity was observed, as demonstrated
by increases in the estrogen concentraon. A rise in
progesterone concentraon was noted in two other
females. As noted, the treatment-induced behavioral
estrus signs without the accompanying rise in
progesterone, observed in the rst two females could be
aributed to a copulaon failure rather than compromised
ovarian funcon. As reported in other works, aer an
inial GnRH treatment, lionesses and cheetahs may
exhibit signs of estrus behavior and become aracted
to males for a few days, although mang may not occur
(Bertschinger et al. 2002).
Conversely, in animals in which a rise in progesterone
concentraon was noted but no behavioral estrus signs
could be observed, a failure in observing estrus signs, a
spontaneous ovulaon – or sensorial smuli triggering
ovulaon – may have occurred. Spontaneous ovulaon
has been previously reported in some felines including
all Panthera species, such as the Leopard (Schmidt et al.
1988), Snow Leopard (Brown et al. 1995), Tiger (Graham et
al. 2006), Jaguar (Barnes et al. 2016; Gonzalez et al. 2017)
and African Lion (Schramm et al. 1994) while sensorial
smulaon has induced ovulaon in Jaguars (Jorge-Neto
et al. 2020). In one lioness, shortly aer placing the
implant, no behavioral estrus signs were observed, nor
was there a rise in progesterone levels. This may be due
Journal of Threatened Taxa | www.threatenedtaxa.org | 26 August 2020 | 12(11): 16469–16477
Suppression of ovarian acvity in a capve African Lion Braga et al.
16476
JTT
to the presence of acve luteal ssue from a previous
follicular cycle and/or due to individual variaons.
Our results reinforce the importance of using non-
invasive monitoring as an alternave for hormonal
assessment, especially in wild animals. Blood collecon
is not only a stressful event and can itself cause changes
in hormonal concentraons (Sheri et al. 2011), but also
does not allow successive collecons for longer studies,
such as monitoring of ovarian cyclicity (Sgai et al. 2015).
Many studies in several species have been developed
and validated for the longitudinal measurement of
hormonal metabolites, both for glucocorcoids (Sinhorini
et al. 2020) and steroids, enabling eecve reproducve
monitoring with fecal matrix (Monfort et al. 1997; Van
Meter et al. 2008). These studies demonstrated ecient
results without the need to perform a serum endocrine
evaluaon.
In conclusion, long-term treatment with a GnRH
agonist has been shown to be extremely eecve in
inhibing the synthesis and liberaon of FSH and LH from
the pituitary, and as a result, ceasing ovarian acvity in
female African lions for 28.67 ± 5.86 months. The duraon
of contracepon, however, may vary among individuals,
with the added risk of some females not returning to
normal ovarian acvity, rendering that female inferle.
It is strongly suggested that further studies invesgate
the long-term anferlity eects of GnRH agonists in this
species.
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Resumo: Com o objevo de avaliar a ecincia de um tratamento
contracepvo para a supresso cclica ovariana em leoas africanas
(Panthera leo) usando um bioimplante com agonista GnRH, foram
ulizados ensaios no invasivos de esteroides fecais associados 
observao de comportamento estral pelo perodo de 36 meses. Cinco
fmeas adultas em caveiro, mandas com um macho vasectomizado,
receberam subcutaneamente um implante de 9,4mg de acetato de
deslorelina. O tratamento inicialmente esmulou o comportamento
estral, juntamente com a avidade ovariana, demonstrada pelo
aumento de estrognio em duas leoas. Um aumento na concentrao
de progesterona em outros dois animais sugeriu uma possvel ovulao
induzida pelo tratamento. Após o perodo inicial, a deslorelina impediu
a avidade ovariana por pelo menos 22 meses. Duas fmeas exibiram
sinais de estro comportamental após 22 e 31 meses. Uma terceira leoa
com aumento da concentrao de estrognio no apresentou sinais
comportamentais de estro ou consequente aumento de progesterona
at 33 meses após o implante, sugerindo uma possvel retomada da
avidade ovariana. Uma fmea no exibiu nenhum sinal de estro
comportamental nem um aumento nos nveis de esteroides após o
estro induzido pelo tratamento durante todo o experimento (36
meses). Uma leoa morreu após 15 meses sem exibir sinais de estro ou
um aumento no nvel de progesterona. No entanto, a concentrao de
estrognio aumentou 12 meses após o implante, sugerindo a retomada
da avidade ovariana. O estudo mostrou que o tratamento a longo
prazo com um agonista da GnRH pode ser extremamente ecaz como
tratamento contracepvo em leoas africanas; no entanto, a durao
da contracepo pode variar entre os indivduos e pode assumir o risco
de perda permanente da avidade ovariana normal.
Threatened Taxa
Author contribuons: DPAF Braga, CS Pizzuo and MABV Guimares conceived,
designed, and directed the study. DPAF Braga, CS Pizzuo and PF Viau
performed the experiments. SHR Correa, CA Oliveira, DPAF Braga, CS Pizzuo
and MABV Guimares analyzed and interpreted the data. DPAF Braga wrote the
manuscript. CS Pizzuo, DA Roseneld and PN Jorge-Neto crically revised the
manuscript. All authors approved the manuscript for publicaon.
... Not surprisingly, the focus has mostly been on carnivores. [5][6][7][8][9]11,[32][33][34]54 Fewer reports have been published for deslorelin use in other mammalian taxa (e.g., ungulates, 44,45 primates, 12,50 and bats 37,38 ). A number of reports have been published for marsupials, 14,21,26-28,60 like-ly because Suprelorin was developed in Australia and has been available there longer. ...
Article
The Association of Zoos and Aquariums Reproductive Management Center (RMC) in the US and the European Association of Zoos and Aquaria Reproductive Management Group (RMG) in Europe monitor efficacy of contraceptive products in participating institutions and use those results to inform contraceptive recommendations. This study used the joint RMC-RMG Contraception Database to analyze efficacy of deslorelin implants (Suprelorin®), a contraceptive used in a wide range of mammalian taxa. More recently its use has increased in birds and in some reptiles and fish. Deslorelin, a gonadotropin-releasing hormone (GnRH) agonist, stimulates the reproductive system before downregulating receptors on pituitary cells that produce hormones that stimulate gonadal steroids in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively. Nevertheless, it has been used mostly in females. Efficacy has been high in mammals, with failures resulting in offspring in only 1.3% of treated individuals and 0.5% of treatment bouts. The failure rate has been higher in birds, with 14.7% of individuals in 7.2% of bouts producing eggs, perhaps reflecting differences in avian GnRH molecules. Too few reptiles and fish have been treated for meaningful analysis. Although deslorelin appears very safe, a possible exception exists in carnivores, because the stimulatory phase can result in ovulation and subsequent sustained progesterone secretion that may cause endometrial pathology. However, the stimulatory phase can be prevented by treatment with megestrol acetate for 7 d before and 7 d after implant insertion. The two current formulations of Suprelorin are effective for minimums of 6 (4.7 mg) or 12 mo (9.4 mg). The data indicate that Suprelorin is an effective and safe contraceptive option for female mammals, although it may not be effective in males of some mammalian species. Further research is needed to ascertain its usefulness in nonmammalian taxa.
... Not surprisingly, the focus has mostly been on carnivores. [5][6][7][8][9]11,[32][33][34]54 Fewer reports have been published for deslorelin use in other mammalian taxa (e.g., ungulates, 44,45 primates, 12,50 and bats 37,38 ). A number of reports have been published for marsupials, 14,21,26-28,60 like-ly because Suprelorin was developed in Australia and has been available there longer. ...
... Not surprisingly, the focus has mostly been on carnivores. [5][6][7][8][9]11,[32][33][34]54 Fewer reports have been published for deslorelin use in other mammalian taxa (e.g., ungulates, 44,45 primates, 12,50 and bats 37,38 ). A number of reports have been published for marsupials, 14,21,26-28,60 like-ly because Suprelorin was developed in Australia and has been available there longer. ...
Preprint
The AZA Reproductive Management Center (RMC) in the U.S. and the EAZA Reproductive Management Group (RMG) in Europe cooperate with the Reproductive Health Surveillance Program to monitor efficacy, reversibility and safety of contraceptive products in participating institutions, using those results to inform contraceptive recommendations. This study used the RMC/RMG Database to analyze efficacy of deslorelin implants (Suprelorin®), which have become a popular contraceptive option for use for a wide range of mammalian taxa, especially carnivores. More recently their use has also increased in birds and even in some reptiles and fish. Deslorelin, a gonadotropin hormone-releasing hormone (GnRH) agonist, first briefly stimulates the reproductive system before down-regulating receptors on cells that produce the pituitary hormones that stimulate gonadal hormones in both males (testosterone) and females (estradiol and progesterone), interrupting sperm production and ovulation, respectively.
Full-text available
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Big cats are apex predators with an essential role in global ecosystems. The One Conservation concept proposes artificial reproduction as one of the tools to reduce the vulnerability of these species. This manuscript aimed to assess what is new in big cat reproduction in the last decade. Knowledge of reproductive physiology and behavior is the first step towards developing reproductive technologies in wild animals. In big cats, copulatory behavior is of fundamental importance because they need ovulation induction mechanisms, which can be mechanical, sensory, or via the administration of the luteinizing hormone. The success in neonatal care represents the success of reproductive technology in females. In the last decade, successful artificial insemination was only reported in Siberian tigers and Anatolian leopards. Jaguar artificial insemination focuses on research at the Reprocon Institute, exchanging genetic material between in situ and ex situ environments thru artificial insemination. The technique of choice is laparoscopic ovum pick-up to obtain high-quality viable oocytes. The production of in vitro embryos faces challenges for the efficient maturation of oocytes and their efficient vitrification. Reproductive technologies need in-depth studies in big cats to achieve the repeatability necessary for efficient application in conservation.
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Deslorelin (Suprelorin®; Virbac) is a gonadotropin-releasing hormone (GnRH) agonist licensed in select countries for the long-term suppression of fertility in adult male dogs and male ferrets. This article summarizes studies investigating the use of deslorelin implants for the long-term suppression of fertility in male and female domestic cats. Slow-release deslorelin implants have been shown to generate effective, safe and reversible long-term contraception in male and female cats. In pubertal cats, a 4.7 mg deslorelin implant suppressed steroid sex hormones for an average of approximately 20 months (range 15-25 months) in males and an average of approximately 24 months (range 16-37 months) in females. Reversibility has been demonstrated by fertile matings approximately 2 years post-treatment in both male and female adult cats. In prepubertal female cats of approximately 4 months of age, puberty was postponed to an average of approximately 10 months of age (range 6-15 months) by a 4.7 mg deslorelin implant. The large variability in the duration of suppression of gonadal activity makes the definition of the optimal time for reimplantation quite challenging. In addition, the temporary stimulation phase occurring in the weeks following deslorelin implantation can induce in adult female cats a fertile estrus that needs to be managed to avoid unwanted pregnancy. Longer duration and larger scale controlled field studies implementing blinding, a negative control group and a carefully controlled randomization to each group are needed. Furthermore, the effects of repeated treatment need to be investigated. Finally, the effect of treatment on growth and bone quality of prepubertal cats needs to be assessed. However, the ease of use, long-lasting effects and reversibility of deslorelin implants are strong positive points supporting their use for controlling feline reproduction. © The Author(s) 2015.
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Conservationists often advocate for landscape approaches to wildlife management while others argue for physical separation between protected species and human communities, but direct empirical comparisons of these alternatives are scarce. We relate African lion population densities and population trends to contrasting management practices across 42 sites in 11 countries. Lion populations in fenced reserves are significantly closer to their estimated carrying capacities than unfenced populations. Whereas fenced reserves can maintain lions at 80% of their potential densities on annual management budgets of $500 km-2 , unfenced populations require budgets in excess of $2000 km-2 to attain half their potential densities. Lions in fenced reserves are primarily limited by density dependence, but lions in unfenced reserves are highly sensitive to human population densities in surrounding communities, and unfenced populations are frequently subjected to density-independent factors. Nearly half the unfenced lion populations may decline to near extinction over the next 20-40 years.
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Large carnivores have declined worldwide, largely through conflict with people. Here, we quantify the impact of lethal control, associated with livestock depredation, on a population of African lions (Panthera leo) living outside protected areas. Farmers shot lions only in response to livestock attacks. Nevertheless, adult mortality was high and a simple model predicted that the population was marginally stable or slowly declining. Mortality was four times higher among lions radio-collared in association with attacks on livestock, than among lions with no known history of stock killing, suggesting that some animals were habitual stock killers. Known stock killers also experienced lower reproductive success; hence there was strong artificial selection against stock-killing behaviour. In addition, mortality was higher among lions whose home ranges overlapped a property where non-traditional livestock husbandry was associated with chronic depredation by lions. This 180 km 2 ranch acted as a sink that directly affected lions over more than 2000 km 2 and may have undermined the viability of the study population. Our results suggest that sustainable coexistence of lions and people demands livestock husbandry that effectively deters predators from acquiring stock-killing behaviour, but that lethal control may play an important role in avoiding the spread of such behaviours through the population.
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The aim of this study was to develop a method for long-term but reversible inhibition of oestrous cycles in female cats by downregulation of GnRH receptors with deslorelin released from a long-acting implant. In a blind study with mature cats (n = 20), a 6 mg deslorelin implant was administered s.c. to ten cats and a placebo implant was administered to ten cats. Occurrence of oestrus and general health were observed daily, and individual faecal samples were collected at 3 day intervals for 14 months and analysed for oestradiol content. All the placebo-treated queens continued to undergo normal oestrous cycles during the study. Oestrus was accompanied by peaks in oestradiol concentrations of > or = 20 ng g-1 faeces. Treatment with deslorelin initially stimulated oestradiol release, which accompanied treatment-induced ovulations. Thereafter, oestradiol concentrations decreased to 1-10 ng g-1 faeces and remained low for extended periods. Observations of small increases in oestradiol concentrations in one cat led to a second treatment with 6 mg deslorelin in five cats on day 155 after first treatment. Faecal oestradiol concentrations remained < 20 ng g-1 faeces in the five single treatment cats for 8.0, 8.5, 11.0 and 14.0 (two cats) months. Cats receiving two implants had the first oestradiol peak > 20 ng g-1 faeces after treatment at 7.5, 11.0 (two cats), 11.5 and 14.0 months. After 14 months, two cats had returned to normal cyclic activity, two had irregular small oestrogen peaks and six showed no cyclic activity. For months 2-5, 6-10 and 11-14, oestrogen values in treated cats were significantly different from control values (P < 0.001, 0.05 and 0.02, respectively). Differences in oestrogen concentration between control cats and cats that were treated twice were significant (P < 0.001) during months 6-10 only. The general health of treated cats was unchanged throughout the study. These results confirm that deslorelin can effectively suppress ovarian activity in domestic cats, but that the duration of suppression varies among individuals.
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Although there is some dissent, the animal protection community generally supports the concept of wildlife contraception. However, some contraceptive agents, delivery mechanisms and specific applications will be opposed by animal welfare advocates on environmental, humane or other ethical grounds, and some animal rights advocates may oppose wildlife contraception entirely. The Humane Society of the United States (HSUS) has supported and conducted wildlife contraception studies for more than 10 years. In general, we have invested in contraceptive agents (such as porcine zona pellucida) that we believe will prove environmentally, physiologically and behaviourally benign, and in delivery mechanisms that are narrowly targeted. As we consider contraception to be a major intervention into natural processes, we believe that wildlife contraception should be applied judiciously, locally and in a manner that is sensitive to the needs of animals, humans and ecosystem function.
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