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First published online March 27, 2009
Journal of Experimental Biology 212, 1087-1091 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.024257
Sex-specific developmental plasticity in response to yolk corticosterone in an oviparous lizard
1 Edward Grey Institute, Department of Zoology, University of Oxford, Oxford OX1
3PS, UK
2 School of Biological Sciences, University of Wollongong, Wollongong, NSW 2522,
Australia
3 Department of Animal and Plant Sciences, University of Sheffield, Sheffield
N10 2TN, UK
4 School of Health Sciences, University of Wollongong, Wollongong, NSW 2522,
Australia
Author for correspondence (e-mail: tobias.uller{at}zoo.ox.ac.uk)
Accepted 22 January 2009
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Summary |
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 TOP Summary INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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Key words: Ctenophorus fordi, hormones, phenotypic plasticity
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INTRODUCTION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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;
West-Eberhard, 2003). For
example, steroids produced during embryonic development induce and regulate
differences between the sexes in primary sexual characters, brains and
behaviour (Adkins-Regan, 2005;
Carere and Balthazart, 2007).
This suggests that hormone production by embryos will be highly time and site
specific and subject to strong selection to avoid production of inferior (for
example, intermediate) phenotypes. However, embryos are also subject to
hormone exposure from external sources, which may or may not be adaptive. In
rodents, for example, a by-product of embryonic steroid production is that
hormone leakage between foetuses can modify the absolute or relative hormone
exposure of individual embryos (Ryan and
Vandenbergh, 2002). Such variation in hormone exposure has been
implied in causing morphological, physiological, behavioural and life-history
variation among offspring in both mammals and viviparous lizards (reviewed by
Clark and Galef, 1998;
Ryan and Vandenbergh, 2002;
Uller, 2006).
Increases in maternal hormone profiles during reproduction also have the
potential to affect hormone exposure of offspring. For example, maternal
up-regulation of glucocorticoids
(Wingfield and Kitayski, 2002)
frequently leads to changes in offspring development, including decreased
birth weight, increased anxiety and impaired coping abilities [i.e. the
prenatal stress syndrome (Welberg and
Seckl, 2001)]. Although this is commonly assumed to be detrimental
to offspring fitness, stress-mediated maternal modulation of phenotypic
development could also represent an evolved strategy that maximizes survival
of offspring under certain environmental conditions [adaptive vs
non-adaptive maternal effects (Marshall
and Uller, 2007; Müller
et al., 2007; Uller,
2008)].
The prenatal stress syndrome is often assumed to result from a direct
action of glucocorticoids on embryonic development
(Welberg and Seckl, 2001) but
it is very difficult to disentangle direct effects of maternal glucocorticoids
on offspring development from other changes in the maternal–foetal
relationship that occur during maternal stress
(Uller and Olsson, 2006a).
However, studies of oviparous vertebrates have shown that maternal hormones
are transferred to egg yolk, which provides a system in which the direct
effect of hormones can be experimentally assessed
(Groothuis et al., 2005).
Perhaps surprisingly, given the extensive literature on the prenatal stress
syndrome, the vast majority of work on oviparous species has been conducted on
yolk androgens [which have been shown to have both short- and long-term
consequences for offspring (reviewed by
Groothuis et al., 2005)],
whereas corticosterone has largely been ignored [exceptions
(McCormick, 1998;
McCormick, 1999;
Love et al., 2005;
Hayward et al., 2006;
Love et al., 2008)]. However,
if corticosterone is indeed transferred to the egg yolk, this represents an
important complementary system in which to evaluate the adaptive nature of
maternal programming of offspring during maternal stress for several reasons.
First, studies of maternal transfer of corticosterone to egg yolk could
provide insight into the general developmental responses to corticosterone
exposure per se, rather than maternal effects that are secondary
products of increased maternal corticosteroids. Second, in contrast to
mammals, transfer of corticosterone is constrained to occur during egg
formation only, which may reduce the opportunity for precise and
context-dependent allocation in response to perceived selection on offspring
(Uller, 2008). Third, the
absence of sudden and unpredictable hormone exposure at different stages in
development of embryos in oviparous species could have influenced the ability
to ignore, or capitalize on, hormonal cues.
The roles of maternal hormone transfer as adaptation or constraint are
particularly important when hormones have sex-specific fitness consequences,
as this can lead to sex-specific maternal effects, select for differential sex
allocation and, ultimately, exercise selection on sex determination (reviewed
by Groothuis et al., 2005;
Uller, 2006;
Carere and Blathazart, 2007;
Rutkowska and Badyaev, 2008;
Uller and Badyaev, 2009). For
example, males are commonly more strongly affected by prenatal stress
(Welberg and Seckl, 2001), and
increased maternal corticosterone levels have been experimentally shown to
bias sex ratios of offspring in some birds (e.g.
Pike and Petrie, 2006). This
could be adaptive if it reduces the fitness reduction associated with
combination of male phenotypes and high corticosterone exposure in
ovo (Love et al.,
2005).
In the present paper, we provide descriptive data on yolk corticosterone in an oviparous lizard, the mallee dragon Ctenophorus fordi, and use experimental manipulation of yolk corticosterone to assess its consequences for offspring development and phenotype at hatching. Based on previous data on mammals, birds and fish, we expected to find maternal transfer of corticosterone and that it would have negative consequences on offspring development and survival, in particular for males.
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MATERIALS AND METHODS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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40–60 mm snout to vent length (SVL)] agamid lizard common to arid
and semi-arid habitats in southern Australia. It emerges from hibernation in
late August to mid September, and females produce between one and four
clutches of two to five eggs [the large majority of clutches having two eggs
only (Uller and Olsson 2006b;
Uller and Olsson, 2009)] over
the reproductive season, which represents the total lifetime reproductive
output for the majority of individuals as survival into the second year is low
(Cogger, 1978). The mating
system is polygynandrous and males are not territorial.
Gravid female mallee dragons from a population in Yathong Nature Reserve,
NSW, were captured by noosing just before oviposition over the reproductive
season in 2005 for assessment of natural variation in yolk hormones. They were
housed individually in cages (645x413x347 mm) until oviposition
according to standard procedures at the University of Wollongong (for details,
see Uller and Olsson, 2006b;
Uller et al., 2007). Eggs were
sampled within 12 h of oviposition, weighed to the nearest 0.01 g and
immediately frozen for future hormone assays (see below). All eggs from nine
clutches and one single egg from an additional 16 clutches were sampled for
analyses of yolk testosterone and corticosterone content (N=38),
which was subsequently used as reference for experimental elevation of yolk
hormones in 2007 (see below).
In 2007, gravid females from the same population were captured and housed
as above. However, rather than being frozen, each experimental egg was
injected with 200 pg of corticosterone dissolved in 1 µl sesame oil, and
each control egg was injected with 1 µl sesame oil. We alternated clutches
so that every second clutch received hormone injections and the others
received vehicle injection only. The injected amount of corticosterone
represents approximately 1.5–3 standard errors of the mean amount of
corticosterone in C. fordi eggs and consequently should correspond
well to naturally high levels (and is well below the maximum hormone levels
found in eggs in the present study; see Results). The injection was performed
through the most pointed end of the egg, and the needle was inserted
approximately one-third into the egg yolk. Eggs were incubated individually in
plastic cups with sterilized vermiculite mixed with sterilized water (volume
ratio 7:1) and incubated at 29°C, which has been shown to minimize
embryonic mortality in this species (Uller
et al., 2008). Incubators were checked daily for hatchlings, which
were measured (SVL and total length to the nearest 0.5 mm), weighed (to the
nearest 0.01 g) and sexed using eversion of the hemipenes
(Harlow, 1996).
Hormone assay
Lizard eggs were weighed and the shell removed, after which they were
weighed separately to determine mass of the egg yolk [albumen forms a very
minor part of mallee dragon eggs (for a review, see
Thompson and Speake, 2004)].
The contents of each egg were placed in a glass tube containing 500 µl of
EIA assay buffer (Cayman Chemical, Ann Arbor, MI, USA) and homogenised using
glass beads. Each tube was spiked with tritiated corticosterone (approximately
2000 c.p.m. (75 Bq) in 20 µl; Amersham, Buckinghamshire, UK) to allow
calculation of post-extraction hormone recovery. Contents of tubes were mixed
and incubated at 4°C overnight. Testosterone (T) and corticosterone (CORT)
were extracted from egg contents based on the methods of Schwabl
(Schwabl, 1993). Briefly, each
sample was extracted twice for 90 min in 3 ml of a 30:70 (v:v) mixture of
petroleum ether and diethyl ether. Ether extracts were decanted after freezing
the aqueous fraction in methanol-dry ice. The two extracts were combined,
dried over a stream of nitrogen gas, reconstituted in 50 ml ethanol, diluted
1:5 in buffer and stored at –20°C until assayed.
Testosterone and corticosterone levels were measured using Cayman EIA assay kits (#582701 and #500651, respectively). All samples were assayed on a single plate, thus eliminating interplate variation. In addition, a 50 µl aliquot of each sample extract was counted in a beta counter to determine percent recovery of the tritiated corticosterone spike. Because our preliminary tests showed very low concentrations of testosterone and corticosterone in lizard eggs, we opted not to purify steroids by column chromatography, potentially reducing concentrations further. Thus, we only determined recovery efficiency in individual samples for corticosterone, and final corticosterone levels were adjusted to account for individual sample recovery. To account for extraction loss of testosterone we applied an average 65% recovery to all eggs based on our previous analyses of testosterone in agamid eggs (L.A., unpublished data).
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RESULTS |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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2=19.0,
P=0.021 and 2=17.7, P=0.024, respectively).
There was a significant positive correlation between the total amount of
corticosterone and testosterone (using means per clutch for clutches for which
we had more than one egg; r=0.83, P<0.001) whereas
neither of the hormones was correlated with egg size (both P>0.40)
or oviposition date (both P>0.2). Omitting clutches for which we
could not find any detectable amounts of hormones resulted in similar patterns
(r=0.73, P=0.008), as did the removal of an outlier
(T=105.6, CORT=1836.0; r=0.64, P=0.035)
(Fig. 1). However, it should be
noted that this outlier represented the mean of two eggs, both of which had
very high hormone content, and therefore is likely to reflect biologically
relevant levels.
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An experimental increase in yolk corticosterone did not have a significant
effect on egg mortality or offspring sex ratio (logistic regressions;
2=1.21, P=0.26 and 2=0.48,
P=0.49, respectively; hatching success was 85.4% and 90.8% for
corticosterone-treated and control eggs, respectively). A linear mixed model
with sex and treatment as fixed factors, clutch identity as a random factor
and egg mass as a covariate showed no significant effect of sex, treatment or
egg mass on incubation time (all P>0.5). Furthermore, there was no
overall significant effect of the treatment on hatchling mass, SVL or total
length, nor were there any interactive effects with egg mass
(Table 1). However, there was a
significant interaction between offspring sex and egg treatment on measures of
offspring size at hatching, which resulted from an opposite effect of yolk
corticosterone on males and females. Males from corticosterone-injected eggs
were smaller and lighter than males from control eggs, whereas females from
corticosterone eggs were larger and heavier than control females
(Table 1;
Fig. 2). Post-hoc
tests failed to reveal a significant effect of treatment within each sex (all
P>0.05), but statistical power is reduced as a result of
relatively small sample sizes. The interaction effect on body mass disappeared
when we controlled for skeletal size (i.e. SVL; treatment x sex;
F1,76.5=2.22, P=0.14).
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DISCUSSION |
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TOPSummaryINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONReferences |
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There was a large variation among clutches in corticosterone content.
Furthermore, yolk corticosterone and testosterone showed a positive
covariation. Whereas testosterone can be locally produced in the ovary,
corticosteroid concentration in eggs has been suggested to reflect passive
transfer from plasma to eggs, with little scope for regulation
(Groothuis and Schwabl, 2008).
Regardless, it is clear that maternal corticosterone can be found in bird,
lizard and fish egg yolk in sufficiently high levels to affect offspring
development (e.g. McCormick,
1999; Hayward and Wingfield,
2004), although its consequences for offspring development in
oviparous animals are poorly understood.
Administration of corticosterone to mothers, or increased maternal stress,
in viviparous species induces a number of different effects in the offspring
(reviewed by Weinstock, 2001;
Welberg and Seckl, 2001).
Nevertheless, in viviparous animals it is unclear whether such effects are
directly caused by embryonic exposure to steroids transferred from the mother
or by other changes in maternal physiology resulting from increased
corticosterone levels [for discussion, see Uller and Olsson
(Uller and Olsson, 2006a)].
For example, studies of both mammals and viviparous lizards have found effects
on offspring size, body condition and behaviour of juveniles (e.g.
de Fraipont et al., 2000;
Welberg and Seckl, 2001;
Meylan and Clobert, 2005).
However, experimental manipulation of corticosterone exposure of offspring
via hormone injection into eggs in the ovo-viviparous lizard
Lacerta vivipara suggested that only behavioural changes are directly
caused by corticosterone [although sex-specific effects were not considered
(Uller and Olsson, 2006a)].
Oviparous vertebrates allow an alternative system in which to explore these
effects and their adaptive significance, which may differ compared with
viviparous species where the maternal–foetal relationship is both more
intimate and prolonged. Furthermore, there is substantial variation in the
length of intrauterine retention of eggs in squamate reptiles [mallee dragons
being at the very early stage (Uller et
al., 2007)], which may be of interest from a comparative
perspective on maternal stress during reproduction and its effects on
offspring development.
In oviparous vertebrates, glucocorticosteroid exposure during development
has been shown to affect behaviour
(Hayward and Wingfield, 2006),
growth and mortality (McCormick,
1999; Hayward and Wingfield,
2004; Warner et al.,
2009) (see also Sinervo and
DeNardo, 1996; Love et al.,
2005) and there is some evidence for sex-specific plasticity in
quail (Hayward et al., 2006).
Furthermore, high levels of prenatal corticosterone seem to reduce survival of
male embryos in the jacky dragon [Amphibolurus muricatus
(Warner et al., 2009)] but
increase survival of male (but not female) offspring post-parturition in the
viviparous common lizard [Lacerta vivipara
(Meylan and Clobert, 2005)].
Despite the fact that corticosterone exposure generally reduces size at
hatching or birth and that males seem to be more strongly affected, the
positive effect on body size in females in our study, and the contrasting
results for other lizards [including another Australian agamid (Warner et al.,
2008)], suggests that developmental plasticity in response to corticosterone
can evolve. Interestingly, a positive effect on size in female, but not male,
hatchlings was also found in corticosterone-implanted female Uta
stansburiana (Sinervo and DeNardo,
1996), which could represent convergent evolution via
selection on sex-specific sensitivity.
Size at hatching is under positive selection in the mallee dragon
via a positive effect on survival and size at the onset of breeding
(T.U. and M.O., unpublished data). Thus, transfer of corticosterone [and
testosterone (Uller et al.,
2007)] to the egg yolk and prenatal sensitivity to hormone
exposure should be under selection. Whereas the evidence for sex-specific
effects of yolk testosterone in this species is indirect [via
sex-specific fitness consequences of size at maturity
(Uller and Olsson, 2006b;
Uller et al., 2007)], the
present study clearly shows that the sexes may respond differently to
increased corticosteroids in terms of size at hatching and potentially
survival via the link between hatchling size and survival to
maturation. The small within-clutch variation in yolk steroids and lack of sex
ratio adjustment (Uller and Olsson,
2006b; Uller et al.,
2008) suggest that sex-specific hormone allocation does not occur
in C. fordi [possibly because of similar oocyte exposure to hormones
as a result of overlapping growth (Badyaev
et al., 2006; Uller,
2006)], despite the fact that the present study may indicate
sex-specific optima. However, it should be pointed out that results from
phenotypic engineering studies must be interpreted with caution as they only
identify direct effects of the manipulated factor (in this case, yolk
corticosterone), not the potential ways in which such effects could be
accommodated developmentally and evolutionarily. For example, it has been
suggested that yolk antioxidants can compensate for detrimental effects of
high testosterone exposure in ovo (e.g.
Royle et al., 2001), and
similar pre- or post-natal compensatory mechanisms may exist for
corticosterone, for example via (sex-specific) behavioural adjustment
or growth (Meylan and Clobert,
2005; Uller and Olsson,
2006a). Furthermore, maternal effects may be environment
dependent, in particular if they have evolved to enable a match between
offspring phenotype and offspring environment
(Love et al., 2005;
Uller, 2008). Ultimately,
combining correlative and experimental studies with estimates of fitness under
ecologically relevant contexts is required to understand the causes and
consequences of hormone-mediated maternal effects
(Groothuis et al., 2005;
Müller et al., 2007;
Groothuis and Schwabl, 2008;
Uller, 2008).
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Footnotes |
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References |
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