skip to main content

Title: Environmental signaling: from environmental estrogens to endocrine‐disrupting chemicals and beyond

The landmark report (Herbstet al. 1971) linking prenatal treatment with a synthetic estrogen, diethylstilbestrol (DES), to cancer at puberty in women whose mothers took the drug while pregnant ushered in an era of research on delayed effects of such exposures on functional outcomes in offspring. An animal model developed in our laboratory at the National Institute of Environmental Health Sciences confirmed thatDESwas the carcinogen and exposure toDEScaused, as well, functional alterations in the reproductive, endocrine, and immune systems of male and female mice treated in utero.DESwas also being used in agriculture and we discovered, at the first meeting onEstrogens in the Environmentin 1979 (Estrogens in the Environment, 1980), that many environmental contaminants were also estrogenic. Many laboratories sought to discern the basis for estrogenicity in environmental chemicals and to discover other hormonally active xenobiotics. Our laboratory elucidated howDESand other estrogenic compounds worked by altering differentiation through epigenetic gene imprinting, helping explain the transgenerational effects found in mice and humans. At theWingspread Conference on the Human‐Wildlife Connectionin 1991 (Advances in Modern Environmental Toxicology, 1992), we learned that environmental disruption of the endocrine system occurred in many species and phyla, and the term endocrine disruption was introduced. Further findings of transgenerational effects of environmental agents that mimicked or blocked various reproductive hormones and the ubiquity of environmental signals, such as bisphenol A increased concern for human and ecological health. Scientists began to look at other endocrine system aspects, such as cardiovascular and immune function, and other nuclear receptors, with important observations regarding obesity and metabolism. Laboratories, such as ours, are now using stem cells to try to understand the mechanisms by which various environmental signals alter cell differentiation. Since 2010, research has shown that trauma and other behavioral inputs can function as ‘environmental signals,’ can be encoded in gene regulation networks in a variety of cells and organs, and can be passed on to subsequent generations. So now we come full circle: environmental chemicals mimic hormones or other metabolic signaling molecules and now behavioral experience can be transduced into chemical signals that also modify gene expression.

more » « less
Author(s) / Creator(s):
Publisher / Repository:
Date Published:
Journal Name:
Page Range / eLocation ID:
p. 684-694
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract

    During the Deepwater Horizon oil spill, vast quantities of a chemical dispersant Corexit 9500 were applied in remediation efforts. In addition to the acute toxicity, it is essential to evaluate Corexit further with a broader scope of long‐term sublethal endocrine endpoints. The American alligator (Alligator mississippiensis) is an excellent organism for such an endeavor. It exhibits temperature‐dependent sex determination, in which egg incubation temperatures during a thermosensitive period (TSP) in embryonic development determine the sex of embryos. Estrogen signals play a critical role in this process. For example, a single exposure to exogenous estrogen during the TSP overrides the effects of temperature and leads to skewed sex ratios. At a concentration of 100 ppm, Corexit significantly induced transcriptional activity of both alligator nuclear estrogen receptors 1 and 2 in vitro in reporter gene assays. To investigate the estrogenic effects of Corexit on gonadal development, alligator eggs were exposed to Corexit at environmentally relevant concentrations (0.25, 2.5 and 25 ppm) before the TSP in ovo. Exposure to Corexit at 0.25 and 25 ppm significantly delayed hatching and growth. Corexit exposure at any treatment level did not affect sex ratios or testicular mRNA abundance as measured at 1‐week post‐hatching, suggesting that the combination of Corexit components did not synergize enough to induce ovarian development in ovo. These results point to a need for further investigations on individual and combined components of Corexit to understand better their long‐term effects on the development and reproductive health of alligators and other coastal aquatic wildlife.

    more » « less
  2. Abstract

    Chromosomal rearrangement can be an important mechanism driving population differentiation and incipient speciation. In the mountain pine beetle (MPB,Dendroctonus ponderosae), deletions on the Y chromosome that are polymorphic among populations are associated with reproductive incompatibility. Here, we usedRADsequencing across the entireMPBrange in western North America to reveal the extent of the phylogeographic differences between Y haplotypes compared to autosomal and X‐linked loci. Clustering and geneflow analyses revealed three distinct Y haplogroups geographically positioned within and on either side of the Great Basin Desert. Despite close geographic proximity between populations on the boundaries of each Y haplogroup, there was extremely low Y haplogroup mixing among populations, and gene flow on the autosomes was reduced across Y haplogroup boundaries. These results are consistent with a previous study suggesting that independent degradation of a recently evolved neo‐Y chromosome in previously isolated populations causes male sterility or inviability among Y haplotype lineages. Phylogeographic results supported historic contraction ofMPBinto three separate Pleistocene glacial refugia followed by postglacial range expansion and secondary contact. Distinct sets ofSNPs were statistically associated with environmental data among the most genetically distinct sets of geographic populations. This finding suggests that the process of adaptation to local climatic conditions is influenced by population genetic structure, with evidence for largely independent evolution in the most genetically isolated Y haplogroup.

    more » « less
  3. Abstract

    Reproductive isolation can be initiated by changes in one or a few key traits that prevent random mating among individuals in a population. During the early stages of speciation, when isolation is often incomplete, there will be a heterogeneous pattern of differentiation across regions of the genome between diverging populations, with loci controlling these key traits appearing the most distinct as a result of strong diversifying selection. In this study, we used Illumina‐sequenced ddRADtags to identify genomewide patterns of differentiation in three recently diverged island populations of theMonarcha castaneiventrisflycatcher of the Solomon Islands. Populations of this species have diverged in plumage colour, and these differences in plumage colour, in turn, are used in conspecific recognition and likely important in reproductive isolation. Previous candidate gene sequencing identified point mutations inMC1RandASIP, both known pigmentation genes, to be associated with the difference in plumage colour between islands. Here, we show that background levels of genomic differentiation based on over 70,000SNPs are extremely low between populations of distinct plumage colour, with no loci reaching the level of differentiation found in either candidate gene. Further, we found that a phylogenetic analysis based on theseSNPs produced a taxonomy wherein the two melanic populations appear to have evolved convergently, rather than from a single common ancestor, in contrast to their original classification as a single subspecies. Finally, we found evidence that the pattern of low genomic differentiation is the result of both incomplete lineage sorting and gene flow between populations.

    more » « less
  4. Abstract

    Identification of genes underlying genomic signatures of natural selection is key to understanding adaptation to local conditions. We used targeted resequencing to identifySNPmarkers in 5321 candidate adaptive genes associated with known immunological, metabolic and growth functions in ovids and other ungulates. We selectively targeted 8161 exons in protein‐coding and nearby 5′ and 3′ untranslated regions of chosen candidate genes. Targeted sequences were taken from bighorn sheep (Ovis canadensis) exon capture data and directly from the domestic sheep genome (Ovis ariesv. 3; oviAri3). The bighorn sheep sequences used in the Dall's sheep (Ovis dalli dalli) exon capture aligned to 2350 genes on the oviAri3 genome with an average of 2 exons each. We developed a microfluidic qPCR‐basedSNPchip to genotype 476 Dall's sheep from locations across their range and test for patterns of selection. Using multiple corroborating approaches (lositanandbayescan), we detected 28SNPloci potentially under selection. We additionally identified candidate loci significantly associated with latitude, longitude, precipitation and temperature, suggesting local environmental adaptation. The three methods demonstrated consistent support for natural selection on nine genes with immune and disease‐regulating functions (e.g. Ovar‐DRA,APC,BATF2,MAGEB18), cell regulation signalling pathways (e.g.KRIT1,PI3K,ORRC3), and respiratory health (CYSLTR1). Characterizing adaptive allele distributions from novel genetic techniques will facilitate investigation of the influence of environmental variation on local adaptation of a northern alpine ungulate throughout its range. This research demonstrated the utility of exon capture for gene‐targetedSNPdiscovery and subsequentSNPchip genotyping using low‐quality samples in a nonmodel species.

    more » « less
  5. Abstract

    Despite substantial interest in coevolution's role in diversification, examples of coevolution contributing to speciation have been elusive. Here, we build upon past studies that have shown both coevolution between South Hills crossbills and lodgepole pine (Pinus contorta), and high levels of reproductive isolation between South Hills crossbills and other ecotypes in the North American red crossbill (Loxia curvirostra) complex. We used genotyping by sequencing to generate population genomic data and applied phylogenetic and population genetic analyses to characterize the genetic structure within and among nine of the ecotypes. Although genome‐wide divergence was slight between ecotypes (FST = 0.011–0.035), we found evidence of relative genetic differentiation (as measured byFST) between and genetic cohesiveness within many of them. As expected for nomadic and opportunistic breeders, we detected no evidence of isolation by distance. The one sedentary ecotype, the South Hills crossbill, was genetically most distinct because of elevated divergence at a small number of loci rather than pronounced overall genome‐wide divergence. These findings suggest that mechanisms related to recent local coevolution between South Hills crossbills and lodgepole pine (e.g. strong resource‐based density dependence limiting gene flow) have been associated with genome divergence in the face of gene flow. Our results further characterize a striking example of coevolution driving speciation within perhaps as little as 6000 years.

    more » « less