PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (32)
 

Clipboard (0)
None

Select a Filter Below

Year of Publication
more »
1.  Temperature Shift Alters DNA Methylation and Histone Modification Patterns in Gonadal Aromatase (cyp19a1) Gene in Species with Temperature-Dependent Sex Determination 
PLoS ONE  2016;11(11):e0167362.
The environment surrounding the embryos has a profound impact on the developmental process and phenotypic outcomes of the organism. In species with temperature-dependent sex determination, gonadal sex is determined by the incubation temperature of the eggs. A mechanistic link between temperature and transcriptional regulation of developmental genes, however, remains elusive. In this study, we examine the changes in DNA methylation and histone modification patterns of the aromatase (cyp19a1) gene in embryonic gonads of red-eared slider turtles (Trachemys scripta) subjected to a temperature shift during development. Shifting embryos from a male-producing temperature (MPT) to a female-producing temperature (FPT) at the beginning of the temperature-sensitive period (TSP) resulted in an increase in aromatase mRNA expression while a shift from FPT to MPT resulted in decreased expression. DNA methylation levels at CpG sites in the promoter of the aromatase gene were high (70–90%) at the beginning of TSP, but decreased in embryos that were incubated at constant FPT and those shifted from MPT to the FPT. This decrease in methylation in the promoter inversely correlated with the expected increase in aromatase expression at the FPT. The active demethylation under the FPT was especially prominent at the CpG site upstream of the gonad-specific TATA box at the beginning of TSP and spread downstream of the gene including exon1 as the gonad development progressed. In embryos incubated at FPT, the promoter region was also labeled by canonical transcriptional activation markers, H3K4me3 and RNA polymerase II. A transcriptional repression marker, H3K27me3, was observed in temperature-shifted gonads of both temperature groups, but was not maintained throughout the development in either group. Our findings suggest that DNA hypomethylation and H3K4me3 modification at the aromatase promoter may be a primary mechanism that releases a transcriptional block of aromatase to initiate a cascade of ovarian differentiation.
doi:10.1371/journal.pone.0167362
PMCID: PMC5130277  PMID: 27902763
2.  Multimodal Sex-Related Differences in Infant and in Infant-Directed Maternal Behaviors during Months Three through Twelve of Development 
Developmental psychology  2015;51(10):1351-1366.
Using the concept of sensory and affective experience, this work relates the concepts of socialization and cognitive development to the embodiment of gender in the human infant. Evidence obtained from biweekly observations from 30 children and their mothers observed from age 3 months to age 12 months revealed measurable sex-related differences in how mothers handle and touch their infants. This work offers novel approaches to visualizing combinations of behaviors with the aim of encouraging researchers to think in terms of suites of action rather than singular sensory or motor systems. New avenues of research into the mechanisms which produce sex-related differences in behavior are suggested.
doi:10.1037/dev0000033
PMCID: PMC4580286  PMID: 26372294
gender and development; embodiment; socialization; dynamic systems; three dimensional visualization
3.  The effects of prenatal PCBs on adult social behavior in rats 
Hormones and behavior  2015;73:47-55.
Endocrine disrupting chemical (EDC) exposures during critical periods of development may influence neuronal development and the manifestation of sexually dimorphic sociability and social novelty behaviors in adulthood. In this study, we assessed the effects of gestational exposure to PCBs on the social behavior of males and females later in adulthood. A weakly estrogenic PCB mixture, Aroclor 1221 (A1221, 0.5 or 1 mg/kg) was administered to pregnant Sprague-Dawley rat dams. Both a positive control (estradiol benzoate; EB, 50 μg/kg) and negative control (dimethylsulfoxide; DMSO in sesame oil vehicle) were similarly administered to separate sets of dams. The sexes responded differently in two tasks essential to sociality. Using a three-chamber apparatus that contained a caged, same-sex, gonadectomized stimulus animal and an empty stimulus cage, we found that both sexes showed a strong preference for affiliating with a stimulus animal (vs. an empty cage), an effect that was much more pronounced in the males. In the second task, a novel and a familiar stimulus animal were caged at opposite ends of the same apparatus. Females displayed a higher degree of novelty preference than the males. During both tests, females had significantly higher social approach behaviors while male engaged in significantly more interactive behaviors with the conspecific. Of particular interest, males born of dams that received prenatal A1221 (0.5 mg/kg) exhibited an overall decrease in nose-to-nose investigations. These behavioral data suggest that the males are more sensitive to A1221 treatment than are females. In addition to behavioral analysis, serum corticosterone was measured. Females born of dams treated with A1221 (0.5 mg/kg) had significantly higher concentrations of corticosterone than the DMSO female group; males were unaffected. Females also had significantly higher corticosterone concentrations than did males. Overall, our results suggest that the effects of gestational exposure to PCBs on adult social behavior are relatively limited within this particular paradigm.
doi:10.1016/j.yhbeh.2015.06.002
PMCID: PMC4546928  PMID: 26093262
Endocrine Disrupting Chemicals; Polychlorinated biphenyls; A1221; Nose Touching; Sociability; Social Novelty; Social Recognition; Social Memory; Sexual Dimorphism; Three-chamber test
4.  Nature, Nurture and Epigenetics 
Real life by definition combines heritability (e.g., the legacy of exposures) and experience (e.g. stress during sensitive or ‘critical’ periods), but how to study or even model this interaction has proven difficult. The hoary concept of evaluating traits according to nature vs. nurture continues to persist despite repeated demonstrations that it retards, rather than advances, our understanding of biological processes. Behavioral genetics has proven the obvious, that genes influences behavior and, vice versa, that behavior influences genes. The concept of Genes X Environment (G X E) and its modern variants was viewed as an improvement on nature-nurture but has proven that, except in rare instances, it is not possible to fractionate phenotypes into these constituent elements. The entanglement inherent in terms such as nature-nurture or GXE is a Gordian knot that cannot be dissected or even split. Given that the world today is not what it was less than a century ago, yet the arbitrator (differential survival and reproduction) has stayed constant, de novo principles and practices are needed to better predict what the future holds. Put simply, the transformation that is now occurring within and between individuals as a product of global endocrine disruption is quite independent of what has been regarded as evolution by selection. This new perspective should focus on how epigenetic modifications might revise approaches to understand how the phenotype and, in particular its components, is shaped. In this review we summarize the literature in this developing area, focusing on our research on the fungicide vinclozolin.
doi:10.1016/j.mce.2014.07.013
PMCID: PMC4300943  PMID: 25102229
Transgenerational; epigenetic; vinclozolin; adolescence; stress; emergent; synchronicity
5.  Hazards inherent in interdisciplinary behavioral research 
Frontiers in Zoology  2015;12(Suppl 1):S21.
Many, if not all, questions in biology and psychology today were formulated and considered in depth, though typically in a different language, from the 1700's to the early 1900's. However, because of politics or fashion, some topics fell out of favor or failed to recruit new scientists and hence languished. Despite greatly expanded scholarship in the history of the life sciences in the twentieth century, many such topics have had to be rediscovered in recent years, while much of the wisdom already accrued stays in the older literature and not in active minds. This is particularly true today when scientific advances appear at breakneck speed. It would not be an exaggeration to say that many ‘breakthroughs’ turn out really to be rediscoveries of forgotten observations. Two areas of particular significance to the interdisciplinary study of behavior are the Norms of Reaction (from Biology) and the concept of Plasticity (from Psychology). These and related fields benefit from the perspective of epigenetics so long as rigorous operational definitions are implemented. It is also important to revive Hogben's admonition that the interaction of hereditary and environment cannot be understood outside of the context of development. Five examples of increasing complexity in phenotypic plasticity in brain and behavior are presented to illustrate this perspective.
doi:10.1186/1742-9994-12-S1-S21
PMCID: PMC4722337  PMID: 26816520
transgenerational; synchronicity; ancestral; proximate; nature versus nurture; epigenetics
6.  Neuronal nitric oxide synthase as a substrate for the evolution of pseudosexual behaviour in parthenogenetic whiptail lizard 
Journal of neuroendocrinology  2011;23(3):244-253.
The evolution of neuroendocrine mechanisms governing sex-typical behaviour is poorly understood. An outstanding animal model is the whiptail lizard (Cnemidophorus) as both the ancestral and descendent species still exist. The ancestral little striped whiptail, C. inornatus, consists of males and females, which exhibit sex-specific mating behaviours. The descendent desert grassland whiptail, C. uniparens, consists only of females that alternately exhibit both female-like and male-like pseudosexual behaviour. Castrated male C. inornatus will mount a conspecific in response to exogenous androgen, but some are also sensitive to progesterone. This polymorphism in progesterone sensitivity in the ancestral species may have been involved in evolution of progesterone-mediated male-typical behaviour in the descendant unisexual lizards. We tested if progesterone activates the typically androgenic signalling pathway by investigating hormonal regulation of neuronal nitric oxide synthase (nNOS) using in situ hybridization and NADPH diaphorase histochemistry, a stain for nNOS protein. NADPH diaphorase is widely distributed throughout the brain of both species, but only in the periventricular nucleus of the preoptic area (pvPOA) are there differences between mounting and non-mounting individuals. The number of cells expressing nNOS mRNA and NADPH diaphorase is higher in the pvPOA of individuals that mount in response to progesterone or androgen. Further, the nNOS promoter has both androgen and progesterone response elements, and NADPH diaphorase colocalizes with the progesterone receptor in the pvPOA. These data suggest that a polymorphism in progesterone sensitivity in the sexual ancestor reflects a differential regulation of nNOS and may account for the male-typical behaviour in unisexual whiptail lizards.
doi:10.1111/j.1365-2826.2010.02099.x
PMCID: PMC4509676  PMID: 21126273
progesterone receptor; neuronal nitric oxide synthase; preoptic area; sexual behaviour; parthenogenesis
7.  Epigenetics in Comparative Biology: Why We Should Pay Attention 
The past decade has seen an explosion of articles in scientific journals involving non-genetic influences on phenotype through modulation of gene function without changes in gene sequence. The excitement in modern molecular biology surrounding the impact exerted by the environment on development of the phenotype is focused largely on mechanism and has not incorporated questions asked (and answers provided) by early philosophers, biologists, and psychologists. As such, this emergence of epigenetic studies is somewhat “old wine in new bottles” and represents a reformulation of the old debate of preformationism versus epigenesis—one resolved in the 1800s. Indeed, this tendency to always look forward, with minimal concern or regard of what has gone before, has led to the present situation in which “true” epigenetic studies are believed to consist of one of two schools. The first is primarily medically based and views epigenetic mechanisms as pathways for disease (e.g., “the epigenetics of cancer”). The second is primarily from the basic sciences, particularly molecular genetics, and regards epigenetics as a potentially important mechanism for organisms exposed to variable environments across multiple generations. There is, however, a third, and separate, school based on the historical literature and debates and regards epigenetics as more of a perspective than a phenomenon. Against this backdrop, comparative integrative biologists are particularly well-suited to understand epigenetic phenomena as a way for organisms to respond rapidly with modified phenotypes (relative to natural selection) to changes in the environment. Using evolutionary principles, it is also possible to interpret “sunsetting” of modified phenotypes when environmental conditions result in a disappearance of the epigenetic modification of gene regulation. Comparative integrative biologists also recognize epigenetics as a potentially confounding source of variation in their data. Epigenetic modification of phenotype (molecular, cellular, morphological, physiological, and behavioral) can be highly variable depending upon ancestral environmental exposure and can contribute to apparent “random” noise in collected datasets. Thus, future research should go beyond the study of epigenetic mechanisms at the level of the gene and devote additional investigation of epigenetic outcomes at the level of both the individual organism and how it affects the evolution of populations. This review is the first of seven in this special issue of Integrative and Comparative Biology that addresses in detail these and other key topics in the study of epigenetics.
doi:10.1093/icb/icu013
PMCID: PMC4133572  PMID: 24722321
8.  Sociosexual Investigation in Sexually Experienced, Hormonally Manipulated Male Leopard Geckos: Relation With Phosphorylated DARPP-32 in Dopaminergic Pathways 
Dopaminergic activity is both associated with sociosexual exposure and modulated by sexual experience and hormonal state across vertebrate taxa. Mature leopard geckos, a reptile with temperature-dependent sex determination, have dopaminoceptive nuclei that are influenced by their embryonic environment and sensitive to adult hormonal manipulation. In this study, we exposed hormonally manipulated male leopard geckos from different incubation temperatures to conspecifics and measured their sociosexual investigation, as well as phosphorylated DARPP-32 at Threonine 34 (pDARPP-32) immunoreactivity as a marker for D1 dopamine receptor activity in the nucleus accumbens, striatum, and preoptic area. Social investigation time by males of different incubation temperatures was modulated in opposite directions by exogenous androgen treatment. Males exposed to novel stimuli spent a greater proportion of time investigating females of different incubation temperatures. The time spent investigating females was positively correlated to pDARPP-32 immunoreactivity in the preoptic area. This is the first study quantifying pDARPP-32 in a lizard species, and suggests the protein as a potential marker to measure differences in the dopaminergic pathway in a social setting with consideration of embryonic environment and hormonal state.
doi:10.1002/jez.1891
PMCID: PMC4432236  PMID: 25351686
9.  Distinct actions of ancestral vinclozolin and juvenile stress on neural gene expression in the male rat 
Exposure to the endocrine disrupting chemical vinclozolin during gestation of an F0 generation and/or chronic restraint stress during adolescence of the F3 descendants affects behavior, physiology, and gene expression in the brain. Genes related to the networks of growth factors, signaling peptides, and receptors, steroid hormone receptors and enzymes, and epigenetic related factors were measured using quantitative polymerase chain reaction via Taqman low density arrays targeting 48 genes in the central amygdaloid nucleus, medial amygdaloid nucleus, medial preoptic area (mPOA), lateral hypothalamus (LH), and the ventromedial nucleus of the hypothalamus. We found that growth factors are particularly vulnerable to ancestral exposure in the central and medial amygdala; restraint stress during adolescence affected neural growth factors in the medial amygdala. Signaling peptides were affected by both ancestral exposure and stress during adolescence primarily in hypothalamic nuclei. Steroid hormone receptors and enzymes were strongly affected by restraint stress in the mPOA. Epigenetic related genes were affected by stress in the ventromedial nucleus and by both ancestral exposure and stress during adolescence independently in the central amygdala. It is noteworthy that the LH showed no effects of either manipulation. Gene expression is discussed in the context of behavioral and physiological measures previously published.
doi:10.3389/fgene.2015.00056
PMCID: PMC4345841  PMID: 25784924
endocrine disruption; amygdala; hypothalamus; transgenerational; vinclozolin
10.  Binary Outputs from Unitary Networks 
When considering sex ratios, we have to first define the nature of the question. Are we referring to the gonads, secondary and accessory sex structures, physiology, brain, behavior, or to all of the above elements. If these elements are not concordant, the exceptions can prove illustrative of underlying processes at both the proximate and ultimate levels. At each of these levels, “sex” is the binary outcome resulting from the modulation of conserved networks of genes, proteins, cells, organs, and, in the case of the brain, discrete nuclei. These networks operate at multiple and sequential levels that usually are linear during the lifespan, but in some instances reversals are possible. For example, the gonads arise from a single “anlagen” and, in most instances, ovaries or testes result, although ovotestes are the norm in some species and gonadal reversal a property of other species. Other sexually dimorphic structures differentiate from multiple “anlaga” by reciprocal and sex-specific atrophy/hypertrophy, typically in an exaggerated manner, although the capacity to develop structures characteristic of the opposite gonadal sex remains inherent and intact. A perspective that integrates these different properties are presented here.
doi:10.1093/icb/ict010
PMCID: PMC3836006  PMID: 23559320
11.  Gene bionetworks involved in the epigenetic transgenerational inheritance of altered mate preference: environmental epigenetics and evolutionary biology 
BMC Genomics  2014;15(1):377.
Background
Mate preference behavior is an essential first step in sexual selection and is a critical determinant in evolutionary biology. Previously an environmental compound (the fungicide vinclozolin) was found to promote the epigenetic transgenerational inheritance of an altered sperm epigenome and modified mate preference characteristics for three generations after exposure of a gestating female.
Results
The current study investigated gene networks involved in various regions of the brain that correlated with the altered mate preference behavior in the male and female. Statistically significant correlations of gene clusters and modules were identified to associate with specific mate preference behaviors. This novel systems biology approach identified gene networks (bionetworks) involved in sex-specific mate preference behavior. Observations demonstrate the ability of environmental factors to promote the epigenetic transgenerational inheritance of this altered evolutionary biology determinant.
Conclusions
Combined observations elucidate the potential molecular control of mate preference behavior and suggests environmental epigenetics can have a role in evolutionary biology.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-377) contains supplementary material, which is available to authorized users.
doi:10.1186/1471-2164-15-377
PMCID: PMC4073506  PMID: 24885959
Epigenetics; Brain; Networks; Evolution; Behavior
12.  Androgens coordinate neurotransmitter-related gene expression in male whiptail lizards 
Genes, brain, and behavior  2012;11(7):813-818.
Sex steroid hormones coordinate neurotransmitter systems in the male brain to facilitate sexual behavior. Although neurotransmitter release in the male brain has been well documented, little is known about how androgens orchestrate changes in gene expression of neurotransmitter receptors. We used male whiptail lizards (Cnemidophorus inornatus) to investigate how androgens alter neurotransmitter-related gene expression in brain regions involved in social decision-making. We focused on three neurotransmitter systems involved in male-typical sexual behavior, including the NMDA glutamate receptor, nitric oxide, and dopamine receptors. Here we show that in androgen-treated males, there are coordinated changes in neurotransmitter-related gene expression. In androgen-implanted castrates compared to blank-implanted castrates (control group), we found associated increases in neuronal nitric oxide synthase (nNOS) gene expression in the nucleus accumbens, preoptic area and ventromedial hypothalamus, a decrease of NR1 gene expression (obligate subunit of NMDA receptors) in the medial amygdaloid area and nucleus accumbens, and a decrease in D1 and D2 dopamine receptor gene expression in the nucleus accumbens. Our results support and expand the current model of androgen-mediated gene expression changes of neurotransmitter-related systems that facilitate sexual behavior in males. This also suggests that the proposed evolutionarily ancient reward system that reinforces sexual behavior in amniote vertebrates extends to reptiles.
doi:10.1111/j.1601-183X.2012.00828.x
PMCID: PMC3467320  PMID: 22862958
androgens; neuronal nitric oxide synthase; glutamate; sexual behavior; dopamine receptors
13.  Epigenetic Control of Gonadal Aromatase (cyp19a1) in Temperature-Dependent Sex Determination of Red-Eared Slider Turtles 
PLoS ONE  2013;8(6):e63599.
In the red-eared slider turtle (Trachemys scripta), a species with temperature-dependent sex determination (TSD), the expression of the aromatase gene during gonad development is strictly limited to the female-producing temperature. The underlying mechanism remains unknown. In this study, we identified the upstream 5′-flanking region of the aromatase gene, gonad-specific promoter, and the temperature-dependent DNA methylation signatures during gonad development in the red-eared slider turtle. The 5′-flanking region of the slider aromatase exhibited sequence similarities to the aromatase genes of the American alligator, chicken, quail, and zebra finch. A putative TATA box was located 31 bp upstream of the gonad-specific transcription start site. DNA methylation at the CpG sites between the putative binding sites of the fork head domain factor (FOX) and vertebrate steroidogenic factor 1 (SF1) and adjacent TATA box in the promoter region were significantly lower in embryonic gonads at the female-producing temperature compared the male-producing temperature. A shift from male- to female-, but not from female- to male-, producing temperature changed the level of DNA methylation in gonads. Taken together these results indicate that the temperature, particularly female-producing temperature, allows demethylation at the specific CpG sites of the promoter region which leads the temperature-specific expression of aromatase during gonad development.
doi:10.1371/journal.pone.0063599
PMCID: PMC3676416  PMID: 23762231
14.  Epigenetic synthesis: a need for a new paradigm for evolution in a contaminated world 
Epigenetics is a perspective, not a set of techniques. Molecular biology and genetics are the dominant disciplines in biology today, but practitioners of these fields have only recently ‘rediscovered’ the importance of the environment. This has led to increasing research into molecular epigenetics and the interface between the environment and gene regulation. Beyond the study of epigenetic mechanisms at the level of the gene, more investigation of epigenetic outcomes at the level of both the individual organism and the evolution of the population is needed.
doi:10.3410/B4-18
PMCID: PMC3434969  PMID: 22991583
15.  Epigenetic Modifications of Brain and Behavior: Theory and Practice 
Hormones and Behavior  2010;59(3):393-398.
Evolutionary change is a product of selection. Selection operates on the phenotype, and its consequences are manifest in representation of the genotype in successive generations. Of particular interest to both evolutionary and behavioral biologists is the newly emerging field of epigenetics and behavior. Two broad categories of epigenetic modifications must be distinguished. Context-Dependent epigenetic change can be observed if the environmental factors that bring about the epigenetic modification persists (e.g., the frequency and quality of maternal care modifying the brain and future behavior of the offspring each generation). Because the environment induces epiallelic change, removing the causative factor can reverse a Context-Dependent epigenetic state. Germline-Dependent epigenetic change occurs when the epigenetic imprint is mediated through the germline. Such effects are independent of the causative agent and there is no evidence at present that a Germline-Dependent epigenetic state can be reversed. Finally, only Germline-Dependent epigenetic modifications can be truly transgenerational. Although an individual’s life history is progressive and continuous, it might usefully be viewed as the cumulation of divisions; each period emerging from what has gone before and, at the same time, setting the stage for what follows. These life history stages are somewhat arbitrary, with many traits spanning conventional divisions, but each period tends to have its own characteristic ethologies and particular contribution to neural and behavioral phenotypes. To understand how theses episodes ‘fit’ together, it is necessary to deconstruct early life events and study each period both in its’ own right and how it interacts with the preceding and subsequent stages. Lastly, it seems intuitive that Germline-Dependent and Context-Dependent epigenetic modifications interact, resulting in the individual variation observed in behaviors, but until now this hypothesis has never been tested experimentally.
doi:10.1016/j.yhbeh.2010.07.001
PMCID: PMC3401366  PMID: 20633562
transgenerational; individual variation; life history; prenatal; postnatal; adolescence; litter
16.  Molecular characterization and brain distribution of the progesterone receptor in whiptail lizards 
Progesterone and its nuclear receptor are critical in modulating reproductive physiology and behavior in female and male vertebrates. Whiptail lizards (genus Cnemidophorus) are an excellent model system in which to study the evolution of sexual behavior, as both the ancestral and descendent species exist. Male-typical sexual behavior is mediated by progesterone in both the ancestral species and the descendant all-female species, although the molecular characterization and distribution of the progesterone receptor protein throughout the reptilian brain is not well understood. To better understand the gene targets and ligand binding properties of the progesterone receptor in whiptails, we cloned the promoter and coding sequence of the progesterone receptor and analyzed the predicted protein structure. We next determined the distribution of the progesterone receptor protein and mRNA throughout the brain of C. inornatus and C. uniparens by immunohistochemistry and in situ hybridization. We found the progesterone receptor to be present in many brain regions known to regulate social behavior and processing of stimulus salience across many vertebrates, including the ventral tegmental area, amygdala, nucleus accumbens and several hypothalamic nuclei. Additionally, we quantified immunoreactive cells in the preoptic area and ventromedial hypothalamus in females of both species and males of the ancestral species. We found differences between both species and across ovarian states. Our results significantly extend our understanding of progesterone modulation in the reptilian brain and support the important role of the nuclear progesterone receptor in modulating sexual behavior in reptiles and across vertebrates.
doi:10.1016/j.ygcen.2010.12.010
PMCID: PMC3041865  PMID: 21185292
progesterone receptor; reptile; sexual behavior; social behavior; parthenogenesis
17.  Segregating Variation for Temperature-dependent Sex Determination in a Lizard 
Heredity  2010;106(4):649-660.
Temperature-dependent sex determination (TSD) was first reported in 1966 in an African lizard. It has since been shown that TSD occurs in some fish, several lizards, tuataras, numerous turtles, and all crocodilians. Extreme temperatures can also cause sex reversal in several amphibians and lizards with genotypic sex determination. Research in TSD species indicates that estrogen signaling is important for ovary development and that orthologs of mammalian genes play a role in gonad differentiation. Nevertheless, the mechanism that actually transduces temperature into a biological signal for ovary versus testis development is not known in any species. Classical genetics could be used to identify the loci underlying TSD, but only if there is segregating variation for TSD. Here, we employ the “animal model” to analyze inheritance of sexual phenotype in a 13-generation pedigree of captive leopard geckos, Eublepharis macularius, a TSD reptile. We directly demonstrate genetic variance and genotype-by-temperature interactions for sex determination. Additive genetic variation was significant at a temperature that produces a female-biased sex ratio (30°C) but not at a temperature that produces a male-biased sex ratio (32.5°C). Conversely, dominance variance was significant at the male-biased temperature (32.5°C), but not at the female-biased temperature (30°C). Non-genetic maternal effects on sex determination were negligible in comparison to additive genetic variance, dominance variance, and the primary effect of temperature. These data show for the first time that there is segregating variation for TSD in a reptile and consequently that a QTL analysis would be practicable for identifying the genes underlying TSD.
doi:10.1038/hdy.2010.102
PMCID: PMC2980574  PMID: 20700140
maternal effects; quantitative genetics; reptile; sex ratio; temperature-dependent sex determination
18.  Life Imprints: Living in a Contaminated World 
Environmental Health Perspectives  2011;119(9):1208-1210.
Background: The links between nature and nurture need to be redefined to accommodate anthropogenic chemical contamination. Although some local remediation of contamination has occurred, at the global level this is simply not possible. Contaminants are spread by population migration, by introduction via the food chain, and through air and water currents, even to regions that were never exposed directly to these environmental insults. In recognizing and accepting this worldwide change, we must move on and consider the types of adaptations that could occur as a consequence.
Objectives: We propose a paradigm shift in the field that integrates various disciplines involved in the study of environmental contamination to recognize that contamination is widespread and cannot be remedied at the global level.
Discussion: Greater effort must be placed on integrative and interdisciplinary studies that explicitly illuminate how the causal mechanisms and functional outcomes of related processes operate at each level of biological organization while at the same time revealing the relations among the levels.
Conclusions: To anticipate and understand the future, we must devote more study to what is likely to happen and less to what has happened. Only then will we begin to understand how ancestral environmental exposures act at both the level of the individual and the level of their descendants to influence all aspects of life history.
doi:10.1289/ehp.1103451
PMCID: PMC3230404  PMID: 21571618
endocrine-disrupting chemicals; epigenetics; evolutionary biology; heritable; proximate effect; ultimate effect
19.  Steroid Signaling and Temperature-Dependent Sex Determination – Reviewing the Evidence for Early Action of Estrogen during Ovarian Determination in the Red-Eared Slider Turtle (Trachemys scripta elegans) 
The developmental processes underlying gonadal differentiation are conserved across vertebrates, but the triggers initiating these trajectories are extremely variable. The red-eared slider turtle (Trachemys scripta elegans) exhibits temperature-dependent sex determination (TSD), a system where incubation temperature during a temperature-sensitive period of development determines offspring sex. However, gonadal sex is sensitive to both temperature and hormones during this period – particularly estrogen. We present a model for temperature-based differences in aromatase expression as a critical step in ovarian determination. Localized estrogen production facilitates ovarian development while inhibiting male-specific gene expression. At male-producing temperatures aromatase is not upregulated, thereby allowing testis development.
doi:10.1016/j.semcdb.2008.10.004
PMCID: PMC2695493  PMID: 18992835
temperature-dependent sex determination; Trachemys scripta; estrogen; aromatase; ovary
20.  Analyzing the Coordinated Gene Network Underlying Temperature-Dependent Sex Determination in Reptiles 
Although gonadogenesis has been extensively studied in vertebrates with genetic sex determination, investigations at the molecular level in nontraditional model organisms with temperature-dependent sex determination are a relatively new area of research. Results show that while the key players of the molecular network underlying gonad development appear to be retained, their functions range from conserved to novel roles. In this review, we summarize experiments investigating candidate molecular players underlying temperature-dependent sex determination. We discuss some of the problems encountered unraveling this network, pose potential solutions, and suggest rewarding future directions of research.
doi:10.1016/j.semcdb.2008.10.010
PMCID: PMC2729108  PMID: 19022389
temperature; sex determination; gonad; reptile; development
21.  Steroidogenic enzyme gene expression in the brain of the parthenogenetic whiptail lizard, Cnemidophorus uniparens 
Brain research  2008;1253:129-138.
The steroidogenic enzyme CYP17 is responsible for catalyzing the production of androgenic precursors, while CYP19 converts testosterone to estradiol. De novo neurosteroidogenesis in specific brain regions influences steroid hormone dependent behaviors. In the all-female lizard species Cnemidophorus uniparens, individuals alternately display both male-like mounting and female-like receptivity. Mounting is associated with high circulating concentrations of progesterone following ovulation (PostOv), while receptivity is correlated with estrogen preceding it (PreOv). At a neuroanatomical level, the preoptic area (POA) and ventromedial nucleus of the hypothalamus (VMN) are the foci of the male-typical mounting and female-typical receptivity, respectively. In this study, we indirectly test the hypothesis that the whiptail lizard brain is capable of de novo neurosteroidogenesis by cloning fragments of the genes encoding two steroidogenic enzymes, CYP17 and CYP19, and examining their expression patterns in the C. uniparens brain. Our data indicate that these genes are expressed in the C. uniparens brain, and more importantly in the POA and VMN. Using radioactive in situ hybridization, we measured higher CYP17 mRNA levels in the POA of PostOv lizards compared to receptive PreOv animals; CYP19 mRNA levels in the VMN did not change across the ovarian cycle. To our knowledge, these are the first data suggesting that the reptilian brain is capable of de novo steroidogenesis. This study also supports the idea that non-gonadal sources of steroid hormones locally produced in behaviorally relevant brain loci are central to the mediation of behavioral output.
doi:10.1016/j.brainres.2008.11.071
PMCID: PMC2642926  PMID: 19084508
sexual behavior; androgen; estrogen; sexual differentiation
22.  Epigenetics and its implications for behavioral neuroendocrinology 
Frontiers in neuroendocrinology  2008;29(3):344-357.
Individuals vary in their sociosexual behaviors and reactivity. How the organism interacts with the environment to produce this variation has been a focus in psychology since its inception as a scientific discipline. There is now no question that cumulative experiences throughout life history interact with genetic predispositions to shape the individual’s behavior. Recent evidence suggests that events in past generations may also influence how an individual responds to events in their own life history. Epigenetics is the study of how the environment can affect the genome of the individual during its development as well as the development of its descendants, all without changing the DNA sequence. Several distinctions must be made if this research is to become a staple in behavioral neuroendocrinology. The first distinction concerns perspective, and the need to distinguish and appreciate, the differences between Molecular versus Molar epigenetics. Each has its own lineage of investigation, yet both appear to be unaware of one another. Second, it is important to distinguish the difference between Context-Dependent versus Germline-Dependent epigenetic modifications. In essence the difference is one of the mechanism of heritability or transmission within, as apposed to across, generations. This review illustrates these distinctions while describing several rodent models that have shown particular promise for unraveling the contribution of genetics and the environment on sociosexual behavior. The first focuses on genetically-modified mice and makes the point that the early litter environment alters subsequent brain activity and behavior. This work emphasizes the need to understand behavioral development when doing research with such animals. The second focuses on a new rat model in which the epigenome is permanently imprinted, an effect that crosses generations to impact the descendants without further exposure to the precipitating agent. This work raises the question of how events in generations past can have consequences at both the mechanistic, behavioral, and ultimately evolutionary levels.
doi:10.1016/j.yfrne.2008.01.003
PMCID: PMC2394853  PMID: 18358518
Development; Genetically-modified mice; Knockout; Imprinting; Molar epigenetics; Context-Dependent epigenetic modification; Germline-Dependent epigenetic modification; Neural network; Cytochrome oxidase
23.  Litter Environment Affects Behavior and Brain Metabolic Activity of Adult Knockout Mice 
In mammals, the formative environment for social and anxiety-related behaviors is the family unit; in the case of rodents, this is the litter and the mother-young bond. A deciding factor in this environment is the sex ratio of the litter and, in the case of mice lacking functional copies of gene(s), the ratio of the various genotypes in the litter. Both Sex and Genotype ratios of the litter affect the nature and quality of the individual's behavior later in adulthood, as well as metabolic activity in brain nuclei that underlie these behaviors. Mice were raised in litters reconstituted shortly after to birth to control for sex ratio and genotype ratio (wild type pups versus pups lacking a functional estrogen receptor α). In both males and females, the Sex and Genotype of siblings in the litter affected aggressive behaviors as well as patterns of metabolic activity in limbic nuclei in the social behavior network later in adulthood. Further, this pattern in males varied depending upon the Genotype of their brothers and sisters. Principal Components Analysis revealed two components comprised of several amygdalar and hypothalamic nuclei; the VMH showed strong correlations in both clusters, suggesting its pivotal nature in the organization of two neural networks.
doi:10.3389/neuro.08.012.2009
PMCID: PMC2730751  PMID: 19707539
life history; sex differences; genotype differences; sibling; aggression
24.  Transgenerational Epigenetic Programming of the Brain Transcriptome and Anxiety Behavior 
PLoS ONE  2008;3(11):e3745.
Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.
doi:10.1371/journal.pone.0003745
PMCID: PMC2581440  PMID: 19015723
25.  Hormonal state influences aspects of female mate choice in the Túngara Frog (Physalaemus pustulosus) 
Hormones and behavior  2005;49(4):450-457.
Females alter their mate choices as they transition through different reproductive stages; however, the proximal mechanisms for such behavioral fluctuation are unclear. In many taxa, as females transition through different reproductive stages, there is an associated change in hormone levels; therefore, we examined whether fluctuation in hormone levels serves as a proximal mechanism for within-individual variation in mate choice in female túngara frogs (Physalaemus pustulosus). We manipulated hormone levels of females by administering 0, 10, 100, 500 or 1000 IU of human chorionic gonadotropin (HCG), which is a ligand for luteinizing hormone (LH) receptors and will therefore cause increased gonadal hormone production. Phonotaxis assays were conducted to measure three aspects of mate choice behavior before and after HCG administration; receptivity (response to a conspecific mate signal), permissiveness (response to a signal that is less attractive than conspecific signals) and discrimination (ability to discern signal differences). The probability of response to a conspecific and an artificial hybrid signal significantly increased at the highest HCG doses. The difference in mean response time between pre- and post-HCG tests was significantly different for both the receptivity and permissiveness tests among the five doses. Increased permissiveness, however, was not due to decreased discrimination because females could discriminate between calls even at the highest HCG doses. These hormonal manipulations caused the same behavioral pattern we reported in females as they transitioned through different reproductive stages (Lynch, K.S., Rand, A.S., Ryan, M.J., Wilczynski, W., 2005. Plasticity in female mate choice associated with changing reproductive states. Anim. Behav. 69, 689–699), suggesting that changes in hormone levels can influence the female’s mate choice behavior.
doi:10.1016/j.yhbeh.2005.10.001
PMCID: PMC2581836  PMID: 16277986
Male choice; Receptivity; Reproductive hormones; Anuran

Results 1-25 (32)