Biology subjects

Hsu, B.-Y.

Publications and source records attributed to Hsu, B.-Y..

17 recordsLinked to original sources

bioRxiv2025

Warm and cool temperatures decrease early-life telomere length in wild pied flycatchers

Climate change represents a major challenge for avian species. It is characterized by an increase in average ambient temperatures, but also in occurrence of extreme weather events, such as heat weaves and cold snaps. These abrupt temperature changes can modify the immediate and long-term survival prospects of nestling birds, when their thermoregulatory capacities are still not fully developed. While immediate nestling survival can easily be measured, long-term survival is more challenging to evaluate. Early-life telomere length has been suggested as a potential biomarker of future fitness prospects. To evaluate the potential impact of changes in early-life temperature, we thus experimentally increased (ca. +2.8{degrees}C) and decreased (ca. -1.7{degrees}C) average nestbox temperatures in wild pied flycatchers (Ficedula hypoleuca) during nestling postnatal growth, and measured nestling telomere length before fledging. Shorter telomeres were observed in individuals exposed both to an experimental heating or cooling during growth. Our results suggest that long-term survival prospects or long-term performances of individuals exposed to abrupt changes in early-life temperature may be decreased. O_FIG O_LINKSMALLFIG WIDTH=197 HEIGHT=200 SRC="FIGDIR/small/651824v2_ufig1.gif" ALT="Figure 1"> View larger version (118K): org.highwire.dtl.DTLVardef@2ec526org.highwire.dtl.DTLVardef@915e9borg.highwire.dtl.DTLVardef@1da157borg.highwire.dtl.DTLVardef@b857ce_HPS_FORMAT_FIGEXP M_FIG C_FIG

zoology↗

bioRxiv2024

The effects of early-life ambient temperature on the gut microbiome of a wild bird? an experimental approach

Vertebrate gut microbiome has significant effects on host development, health, and fitness. Multiple external factors contribute to gut microbiome variation, and the role of ambient temperature has gained increasing attention. Yet, temperature effects are often tested in extremes and in captive systems. We experimentally studied the effect of subtle temperature decreases during post-natal development on gut microbiome diversity and composition in wild pied flycatchers (Ficedula hypoleuca). We also performed partial cross-fostering to study the relative contribution of genetic and rearing environment on microbiome. Nest-box cold treatment did not influence gut microbiome diversity or composition, which may be due to the small temperature change, ontogenetic stage, or other factors, such as diet, causing large variation in the data. Rearing environment explained more of the variation in gut microbiome than genetic background, but the variance explained was relatively small. Future studies need to further address the drivers of the large intraspecific variation in microbiome in natural populations.

ecology↗

bioRxiv2023

Activation of Store-Operated Calcium Entry and Mitochondiral Respiration by Enterovirus 71 Is Essential for Viral Replication

Enterovirus (EV) infections disrupt cellular calcium (Ca2+) homeostasis. The EV protein 2B is localized to the endoplasmic reticulum (ER) and causes depletion of ER Ca2+ stores. This depletion coincides with a substantial increase in cytosolic Ca2+ levels driven by extracellular Ca2+ influx. However, the precise mechanism underlying this influx remains elusive. In the present study, we demonstrated that EV71 infections induce store-operated Ca2+ entry (SOCE) by activating the Ca2+ sensor stromal interaction molecule 1 (STIM1), which subsequently interacts with Orai1, a plasma membrane (PM) Ca2+ channel. This finding was supported by confocal imaging, which revealed that STIM1, typically localized in the ER, becomes active and colocalizes with Orai1 at the PM in EV71-infected cells. Pharmacological inhibition of the STIM1-Orai1 interaction and knockdown of either STIM1 or Orai1 significantly reduced virus-induced cytosolic Ca2+ levels and viral replication. Global transcriptome analysis revealed that differentially expressed genes are primarily associated with the mitochondrial electron transport chain (ETC) upon SOCE activation, contributing to enhanced ATP generation and oxygen consumption. This increase in mitochondrial Ca2+ levels is correlated with the mid-stage of virus infection. Furthermore, we demonstrated that high levels of mitochondrial Ca2+ influx led to apoptotic cell death favoring viral release at the late stage of virus infection. Finally, SOCE-dependent EV replication was observed in a mouse intestinal organoid culture, a more physiologically relevant cell system. Our results provide valuable insights into the mechanism through which EV infections induce SOCE-mediated spatial and temporal control of Ca2+ signaling, substantially affecting the virus life cycle. IMPORTANCEHost cell Ca2+ signals play crucial roles in various steps of virus life cycles, including entry, replication, and exit. EV requires increased cytosolic Ca2+ levels for efficient replication, but the precise mechanisms underlying the association between Ca2+ levels and EV replication remain elusive. Using EV71 as a model virus, we demonstrated that EV71 infection elevated cytosolic Ca2+ levels through store-operated Ca2+ entry activation and progressive Ca2+ mobilization to mitochondria. This led to the upregulation of electron transport chain activity, which is essential for efficient virus replication and apoptotic cell death, facilitating viral release during the mid and late stages of the infectious cycle, respectively. These findings substantially enhance the understanding of how EVs co-opt host cell mechanisms to promote their own life cycle. STIM1 and Orai1 may be novel targets for broad-spectrum host-directed therapeutics against EVs and other viruses that employ similar replication mechanisms.

microbiology↗

bioRxiv2023

Can increased prenatal exposure to thyroid hormones alter physiology and behaviour in the long-term? Insights from an experimental study in Japanese quails.

Maternal thyroid hormones (triiodothyronine T3 and thyroxine T4) are important regulators of embryonic development and gene expression. While maternal thyroid disorders are known to cause developmental issues in humans, variation in maternal thyroid hormones in healthy mothers have also been found to correlate with infant and child phenotypes. This suggests a potential impact of maternal thyroid hormones on offspring phenotype in an eco-evolutionary context. In chickens, prenatal thyroid hormone treatment has been shown to influence embryonic gene expression and postnatal treatment to influence imprinting and learning. However, the potential long-term effects of maternal thyroid hormones on physiology and behaviour are unclear. This study aims to investigate the long-term effects of maternal thyroid hormones on behaviour, plasma thyroid hormone levels and brain gene expression using the Japanese quail (Coturnix japonica) as a model. Egg hormone levels were elevated by injecting unincubated eggs with either saline (control), T3, T4 or a mixture of T3 and T4. Social motivation, boldness and fearfulness to predators were tested shortly after hatching and as adults. Plasma thyroid hormone levels and pallial expression of thyroid hormone receptor A, type 2 deiodinase, and nuclear receptor coactivator 1 were measured in adulthood. We found no evidence that elevated thyroid hormone levels in eggs affected behaviour, plasma hormone levels, or gene expression. This is the first study examining the potential long-term effects of elevated maternal thyroid hormones within the natural range. Although we found no evidence of long-term effects, other traits may still be affected and remain to be studied.

physiology↗

bioRxiv2023

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of gene expression: an experimental study in a wild bird species

Offspring phenotype at birth is determined by its genotype and the prenatal environment including exposure to maternal hormones. Variation in both maternal glucocorticoids and thyroid hormones can affect offspring phenotype. However, the underlying molecular mechanisms shaping the offspring phenotype, especially those contributing to long-lasting effects, remain unclear. Epigenetic changes (such as DNA methylation) have been postulated as mediators of long-lasting effects of early-life environment. In this study, we determined the effects of elevated prenatal glucocorticoid and thyroid hormones on handling stress response (breath rate), DNA methylation and gene expression of glucocorticoid receptor (GCR) and thyroid hormone receptor (THR) in great tit (Parus major). Eggs were injected before incubation onset with corticosterone (main avian glucocorticoid) and/or thyroid hormones (thyroxine and triiodothyronine) to simulate variation in maternal hormone deposition. Breath rate during handling and gene expression of GCR and THR were evaluated 14 days after hatching. Methylation status of GCR and THR genes were analyzed from the longitudinal blood samples taken 7 and 14 days after hatching, as well as in the following autumn. Elevated prenatal corticosterone level significantly increased the breath rate during handling, indicating enhanced stress response and/or metabolism. Prenatal corticosterone manipulation had CpG-site-specific effects on DNA methylation at the GCR putative promoter region, while it did not significantly affect GCR gene expression. GCR expression was negatively associated with earlier hatching date and chick size. THR methylation or expression did not exhibit any significant relationship with the hormonal treatments or the examined covariates, suggesting that TH signaling may be more robust due to its crucial role in development. This study supports the view that maternal corticosterone may influence offspring metabolism and stress response via epigenetic alterations, yet their possible adaptive role in optimizing offspring phenotype to the prevailing conditions, context-dependency, and the underlying molecular interplay needs further research.

evolutionary biology↗

bioRxiv2021

From climate warming to accelerated cellular ageing: an experimental study in wild birds

Climate change is increasing both the average ambient temperature and the frequency and severity of heat waves. While direct mortality induced by heat waves is increasingly reported, sub-lethal effects are also likely to impact wild populations. We hypothesized that accelerated ageing could be a cost of being exposed to higher ambient temperature, especially in early-life when thermoregulatory capacities are not fully developed. We tested this hypothesis in wild great tits (Parus major) by experimentally increasing nest box temperature by ca. 2{degrees}C during postnatal growth and measuring telomere length, a biomarker of cellular ageing predictive of survival prospects in many bird species. While increasing early-life temperature had no detectable effect on growth or survival to fledging, it accelerated telomere shortening, and although non-significantly, reduced medium-term survival from 34% to 19%. Heat-induced telomere shortening was not explained by oxidative stress, but more likely by an increase in energy demand (i.e. higher thyroid hormones levels, increased expression of glucocorticoid receptor, increased mitochondrial density) leading to a reduction in telomere maintenance mechanisms (i.e. non-significant decrease in the gene expression of telomerase and protective shelterin). Our results thus suggest that climate warming can affect rate of ageing in wild birds, with potential impact on population dynamics and persistence.

physiology↗

bioRxiv2021

Prenatal thyroid hormones accelerate postnatal growth and telomere shortening in wild great tits

Early-life environment is known to affect later-life health and disease, which could be mediated by the early-life programming of telomere length, a key hallmark of ageing. According to the fetal programming of telomere biology hypothesis, variation in prenatal exposure to hormones is likely to influence telomere length. Yet the contribution of key metabolic hormones, i.e. thyroid hormones (THs), has been largely ignored. We recently showed that in contrast to predictions, exposure to elevated prenatal THs increased postnatal telomere length in wild collared flycatchers, but the generality of such effect, its underlying proximate mechanisms and consequences on survival have not been investigated. We therefore conducted a comprehensive study evaluating the impact of THs on potential drivers of telomere dynamics (growth, post-natal THs, mitochondria and oxidative stress), telomere length and medium-term survival using wild great tits as a model system. While prenatal THs did not significantly affect telomere length a week after hatching (i.e. day 7), they influenced postnatal telomere shortening (i.e. shorter telomeres at day 14 and the following winter) but not apparent survival. Circulating THs, mitochondrial density or oxidative stress biomarkers were not significantly influenced, whereas TH-supplemented group showed accelerated growth, which may explain the observed delayed effect on telomeres. We discuss several alternative hypotheses that may explain the contrast with our previous findings in flycatchers. Given that shorter telomeres in early life tend to be carried until adulthood and are often associated with decreased survival prospects, the effects of prenatal THs on telomeres may have long-lasting effects on senescence.

evolutionary biology↗

bioRxiv2021

Altricial bird early-stage embryos express the molecular "machinery" to respond to maternal thyroid hormone cues

Maternal hormones, such as thyroid hormones transferred to embryos and eggs, are key signalling pathways to mediate maternal effects. To be able to respond to maternal cues, embryos must express key molecular machinery of the hormone pathways, such as enzymes and receptors. While altricial birds begin thyroid hormone (TH) production only at/after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited in the egg. However, it is not understood, how and when altricial birds express genes in the TH-pathway. For the first time, we measured the expression of key TH-pathway genes in altricial embryos, using two common altricial ecological model species (pied flycatcher, Ficedula hypoleuca and blue tit Cyanistes caeruleus). Deiodinase DIO1 gene expression could not be reliably confirmed in either species, but deiodinase enzyme DIO2 and DIO3 genes were expressed in both species. Given that DIO2 coverts T4 to biologically active T3, and DIO3 mostly T3 to inactive forms of thyroid hormones, our results suggest that embryos may modulate maternal signals. Thyroid hormone receptor (THRA and THRB) and monocarboxyl membrane transporter gene (SLC15A2) were also expressed, enabling TH-responses. Our results suggest that early altricial embryos may be able to respond and potentially modulate maternal signals conveyed by thyroid hormones.

developmental biology↗

bioRxiv2021

Is maternal thyroid hormone deposition subject to a trade-off between self and egg because of iodine? An experimental study in rock pigeon

Maternal hormones constitute a key signalling pathway for mothers to shape offspring phenotype and fitness. Thyroid hormones (THs; triiodothyronine, T3 and thyroxine, T4) are metabolic hormones known to play crucial roles in embryonic development and survival in all vertebrates. During early developmental stages, embryos exclusively rely on the exposure to maternal THs, and maternal hypothyroidism can cause severe embryonic maldevelopment. The TH molecule includes iodine, an element that cannot be synthesised by the organism. Therefore, TH production may become costly when environmental iodine availability is low. This may yield a trade-off for breeding females between allocating the hormones to self or to their eggs, potentially to the extent that it even influences the number of laid eggs. In this study, we investigated whether low dietary iodine may limit TH production and transfer to the eggs in a captive population of Rock pigeons (Columba livia). We provided breeding females with an iodine-restricted (I- diet) or iodine-supplemented diet (I+ diet) and measured the resulting circulating and yolk iodine and TH concentrations and the number of eggs laid. Our iodine-restricted diet successfully decreased both circulating and yolk iodine concentrations compared to the supplemented diet, but not circulating or yolk THs. This indicates that mothers may not be able to independently regulate hormone exposure for self and their embryos. However, egg production was clearly reduced in the I- group, with fewer females laying eggs. This result shows that restricted availability of iodine does induce a cost in terms of egg production. Whether females reduced egg production to preserve THs for themselves or to prevent embryos from exposure to low iodine and/or THs is as yet unclear.

physiology↗

bioRxiv2020

Co-evolved maternal effects selectively eliminate offspring depending on resource availability

Many plants and animals adaptively downsize the number of already-produced propagules if resources become insufficient to raise all of them. In birds, mothers often induce hatching asynchrony by incubating first eggs before last eggs are laid, creating an age/size hierarchy within broods which selectively eliminates the smallest chicks in poor food conditions. However, mothers also deposit more testosterone into late-laid eggs, which boosts competitive abilities of younger chicks, counteracts the competitive hierarchy, and ostensibly creates a paradox. Since testosterone also carries costs, we hypothesized that benefits of maternally deposited testosterone outweigh its costs in good food conditions, but that testosterone has a net detrimental effect in poor food conditions. We found experimental evidence that elevated maternal testosterone in the egg caused higher chick mortality in poor food conditions but better chick growth in good food conditions. These context-dependent effects resolve the paradox, suggesting co-evolution of two maternal effects, and explain inconsistent results of egg hormone manipulations in the literature.

evolutionary biology↗

bioRxiv2020

Born to be young: prenatal thyroid hormones increase early-life telomere length

Prenatal environmental conditions can have lifelong consequences on health and aging. The underlying mechanisms remain nonetheless little understood. Thyroid hormones (THs) are important regulators of embryogenesis transferred from the mother to the embryo. In an avian model, we manipulated embryo exposure to maternal THs through egg injection and investigated the consequences on postnatal growth and aging. We first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus confirming that these two molecular markers are hallmarks of aging in our wild bird model. The experimental elevation of prenatal THs levels had a transient positive effect on postnatal growth. Elevated prenatal THs had no effect on mtDNA copy number but significantly increased telomere length both soon after birth and at the end of the growth period (equivalent to offsetting ca. 4 years of post-growth telomere shortening). These findings suggest that prenatal THs have a key role in setting the biological age at birth, and thus might influence longevity.

physiology↗

bioRxiv2020

Testing for context-dependent effects of maternal thyroid hormones on offspring survival and physiology: an experimental approach manipulating temperature in a wild bird species

Maternal effects via hormonal transfer from the mother to the offspring provide a tool to translate environmental cues to the offspring. Experimental manipulations of maternally transferred hormones have yielded increasingly contradictory results, which may be explained by environment-dependent effects of hormones. Yet context-dependent effects have rarely been experimentally tested. We therefore studied whether maternally transferred thyroid hormones (THs) exert context-dependent effects on offspring survival and physiology by manipulating both egg TH levels and post-hatching nest temperature in wild pied flycatchers (Ficedula hypoleuca) using a full factorial design. We found no clear evidence for context-dependent effects of prenatal THs related to postnatal temperature on growth, survival and potential underlying physiological responses (plasma TH levels, oxidative stress and mitochondrial density). We conclude that future studies should test for other key environmental conditions, such as food availability, to understand potential context-dependent effects of maternally transmitted hormones on offspring, and their role in adapting to changing environments.

ecology↗

bioRxiv2020

Testing different forms of regulation of yolk thyroid hormone transfer in pied flycatchers

Hormones transferred from mothers to their offspring are considered a maternal tool to prepare progeny for expected environmental conditions, increasing maternal fitness. To flexibly influence offspring, mothers should be able to transmit the hormonal signals independent of their own hormonal status. However, the ability to regulate hormone transfer to the next generation is under debate. We studied the transfer of thyroid hormones (THs) to eggs in a bird model. We elevated thyroxine (T4, the prohormone for the biological active triiodothyronine, T3) during egg-laying using T4 implants on females of a wild population of pied flycatchers (Ficedula hypoleuca), and measured plasma and yolk T4 and T3 as a response. To our knowledge, studies that manipulated a prohormone and measured the change in its active metabolites have rarely been conducted. We found an increase in plasma and yolk T4 and no change in T3 concentrations leading to a similar decrease in yolk T3/T4 ratio in response to the T4 treatment in plasma and yolk. This suggests that mothers are able to regulate the conversion of T4 in T3 to avoid potential costs of elevated exposure to the active hormone to herself and to her progeny. Finally, contrary to our predictions, we found no evidence of regulatory mechanisms at the follicle level, which is essential for independent regulation of yolk hormone transfer. Summary statementThyroid hormones have been overlooked in the context of hormone-mediated maternal effects. We found that mothers may regulate yolk thyroid hormone transfer by regulating the conversion of the active form of the hormone.

physiology↗

bioRxiv2019

Inter-specific variation of maternal thyroid hormones associate with migration, mode of development, and captivity: a phylogenetic comparative analysis

Life-history traits vary largely across species and several physiological parameters have been proposed to be associated with life-history variation, such as metabolic rates, glucocorticoids, and oxidative stress. Interestingly, the association between thyroid hormones (THs) and life history variation has never been considered, despite a close interaction between THs and these physiological traits. Because of the crucial effects on embryonic development, THs can also induce transgenerational plasticity when transferred to developing offspring, for instance, via egg yolks in birds. In this study, we compiled a unique data set of maternal yolk THs in 34 bird species across 17 families and 6 orders, and tested for associations with various life-history traits. Our phylogenetic mixed models indicated that both concentrations and total amounts of the two most important forms of THs (T3 and T4) were higher in the eggs of migratory species than in those of resident species, and that there were higher total amounts of T3 in the eggs of precocial species than in those of altricial species. However, maternal THs did not show clear associations with any traits of the pace-of-life syndrome, such as developmental duration, growth rate, or lifespan. When taking environmental factors into account, we found that captive species deposited higher TH concentrations and larger amounts in the egg yolks than wild species. These findings suggest that maternal THs are likely involved in the evolution of life-history variation, or vice versa.

evolutionary biology↗

bioRxiv2019

Elevated exposure to prenatal thyroid hormones affects embryonic mortality but has no effects into adulthood

Maternal thyroid hormones (THs) are known to be crucial in embryonic development in humans, but their influence on other, especially wild, animals remains poorly understood. So far, the studies that experimentally investigated the consequences of maternal THs focused on short-term effects, while early organisational effects with long-term consequences, as shown for other prenatal hormones, could also be expected. In this study, we aimed at investigating both the short- and long-term effects of prenatal THs in a bird species, the Japanese quail Coturnix japonica. We experimentally elevated yolk TH content (the prohormone T4, and its active metabolite T3, as well as a combination of both hormones). We analysed hatching success, embryonic development, offspring growth and oxidative stress as well as their potential organisational effects on reproduction, moult, and oxidative stress in adulthood. We found that eggs injected with both hormones had a higher hatching success compared with control eggs, suggesting conversion of T4 into T3 by the embryo. We detected no other clear short-term or long-term effects of yolk THs. These results suggest that yolk thyroid hormones are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal thyroid hormones will greatly benefit from studies investigating how embryos use and respond to this maternal signalling. Long-term studies on prenatal THs in other taxa in the wild are needed for a better understanding of this hormone-mediated maternal pathway.

physiology↗

bioRxiv2019

Plastic but repeatable: rapid adjustments of mitochondrial function and density during reproduction in a wild bird species

Most of the energy fluxes supporting animal performance flow through mitochondria. Hence, inter-individual differences in performance might be rooted in inter-individual variations in mitochondrial function and density. Furthermore, because the energy required by an individual often changes across life stages, mitochondrial function and density are also expected to show within-individual variation (i.e. plasticity). No study so far has repeatedly measured mitochondrial function and density in the same individuals to simultaneously test for within-individual repeatability and plasticity of mitochondrial traits. Here, we repeatedly measured mitochondrial DNA copy number (a proxy of density) and respiration rates from blood cells of female pied flycatchers (Ficedula hypoleuca) at the incubation and chick-rearing stages. Mitochondrial density and respiration rates were all repeatable (R = [0.45-0.80]), indicating high within-individual consistency in mitochondrial traits across life-history stages. Mitochondrial traits were also plastic, showing a quick (i.e. 10 days) down-regulation from incubation to chick-rearing in mitochondrial density, respiratory activity, and cellular regulation by endogenous substrates and/or ATP demand. These downregulations were partially compensated by an increase in mitochondrial efficiency at the chick-rearing stage. Therefore, our study provides clear evidence for both short-term plasticity and high within-individual consistency in mitochondrial function and density during reproduction in a wild bird species.

physiology↗

bioRxiv2019

Prenatal thyroid hormone exposure increases growth but not oxidative stress in a wild passerine species

Hormones transferred from mothers to their offspring are thought to be a maternal tool for mothers to prepare their progeny for expected environmental conditions, thus increasing fitness. Thyroid hormones (THs) are crucial across vertebrates for embryonic and post-natal development and metabolism. Nevertheless, the studies that investigated the consequences of maternal hormones have mostly focused on steroid hormones and ignored maternally-derived thyroid hormones. In this study, we experimentally elevated yolk thyroid hormones in a wild population of a migratory passerine, the European Pied flycatcher Ficedula hypoleuca. We injected eggs with a mixture of T4 and T3 within the natural range of the species to assess its effects on hatching success, nestling survival, growth and oxidative status (antioxidant enzyme activity, lipid peroxidation and oxidative balance). We found no effects of yolk THs on egg hatchability or nestling survival. Yolk THs increased nestling growth during the second week post hatching, but this potentially beneficial effect did not incur any costs in terms of oxidative stress. The results should stimulate more research on thyroid hormone mediated maternal effects, further studies into the underlying mechanistic pathways for these effects and how they translate into adulthood and fitness.\n\nSummary statementThyroid hormones have been overlooked in the context of hormone-mediated maternal effects. We found that yolk thyroid hormones in a wild bird species increase growth without incurring oxidative stress.

physiology↗