Ambient temperature and the occurrence of intradialytic hypotension in patients receiving hemodialysis.

Background: Intradialytic hypotension (IDH) is a common hemodialysis complication causing adverse outcomes. Despite the well-documented associations of ambient temperatures with fluid removal and pre-dialysis blood pressure (BP), the relationship between ambient temperature and IDH has not been adequately studied. Methods: We conducted a cohort study at a tertiary hospital in southern Taiwan between 1 January 2016 and 31 October 2021. The 24-h pre-hemodialysis mean ambient temperature was determined using hourly readings from the weather station closest to each patient's residence. IDH was defined using Fall40 [systolic BP (SBP) drop of ≥40 mmHg] or Nadir90/100 (SBP <100 if pre-dialysis SBP was ≥160, or SBP <90 mmHg). Multivariate logistic regression with generalizing estimating equations and mediation analysis were utilized. Results: The study examined 110 400 hemodialysis sessions from 182 patients, finding an IDH prevalence of 11.8% and 10.4% as per the Fall40 and Nadir90/100 criteria, respectively. It revealed a reverse J-shaped relationship between ambient temperature and IDH, with a turning point around 27°C. For temperatures under 27°C, a 4°C drop significantly increased the odds ratio of IDH to 1.292 [95% confidence interval (CI) 1.228 to 1.358] and 1.207 (95% CI 1.149 to 1.268) under the Fall40 and Nadir90/100 definitions, respectively. Lower ambient temperatures correlated with higher ultrafiltration, accounting for about 23% of the increased IDH risk. Stratified seasonal analysis indicated that this relationship was consistent in spring, autumn and winter. Conclusion: Lower ambient temperature is significantly associated with an increased risk of IDH below the threshold of 27°C, irrespective of the IDH definition. This study provides further insight into environmental risk factors for IDH in patients undergoing hemodialysis.

From maternal glucocorticoid and thyroid hormones to epigenetic regulation of offspring 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, but the underlying molecular mechanisms, 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) as well as DNA methylation and gene expression of glucocorticoid receptor (GR) and thyroid hormone receptor (THR) in great tits (Parus major). Eggs were injected before incubation onset with corticosterone (the 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 GR and THR were evaluated 14 days after hatching. Methylation status of GR and THR genes was analyzed from the longitudinal blood cells sampled 7 and 14 days after hatching, as well as the following autumn. Elevated prenatal corticosterone level significantly increased the breath rate during handling, indicating an enhanced metabolic stress response. Prenatal corticosterone manipulation had CpG-site-specific effects on DNA methylation at the GR putative promoter region, while it did not significantly affect GR gene expression. GR 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 provides some support to the hypothesis suggesting that maternal corticosterone may influence offspring metabolic 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.

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

The 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, the underlying proximate mechanisms and consequences for 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 the 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.

Application of hybrid fuzzy interval-based machine learning models on financial time series - A case study of Taiwan biotech index during the epidemic period.

In recent years, the use of machine learning to predict stock market indices has emerged as a vital concern in the FinTech domain. However, the inherent nature of point estimation in traditional supervised machine learning models leads to an almost negligible probability of achieving perfect predictions, significantly constraining the applicability of machine learning prediction models. This study employs 4 machine learning models, namely BPN, LSTM, RF, and ELM, to establish predictive models for the Taiwan biotech index during the COVID-19 period. Additionally, it integrates the Gaussian membership function MF from fuzzy theory to develop 4 hybrid fuzzy interval-based machine learning models, evaluating their predictive accuracy through empirical analysis and comparing them with conventional point estimation models. The empirical data is sourced from the financial time series of the "M1722 Listed Biotechnology and Medical Care Index" compiled by the Taiwan Economic Journal during the outbreak of the COVID-19 pandemic, aiming to understand the effectiveness of machine learning models in the face of significant disruptive factors like the pandemic. The findings demonstrate that despite the influence of COVID-19, machine learning remains effective. LSTM performs the best among the models, both in traditional mode and after fuzzy interval enhancement, followed by the ELM and RF models. The predictive results of these three models reach a certain level of accuracy and all outperform the BPN model. Fuzzy-LSTM effectively predicts at a 68% confidence level, while Fuzzy-ELM and Fuzzy-RF yield better results at a 95% confidence level. Fuzzy-BPN exhibits the lowest predictive accuracy. Overall, the fuzzy interval-based LSTM excels in time series prediction, suggesting its potential application in forecasting time series data in financial markets to enhance the efficacy of investment analysis for investors.

Altricial Bird Early-Stage Embryos Express the Molecular "Machinery" to Respond to and Modulate Maternal Thyroid Hormone Cues.

AbstractMaternal hormones, such as thyroid hormones (THs) transferred to embryos and eggs, are key signaling pathways for mediating maternal effects. To be able to respond to maternal cues, embryos must express the key molecular "machinery" of hormone pathways, such as enzymes and receptors. While altricial birds begin TH production only at or after hatching, experimental evidence suggests that their phenotype can be influenced by maternal THs deposited into the egg. However, it is not understood how or 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 by 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 genes DIO2 and DIO3 were expressed in both species. Given that DIO2 converts thyroxine to biologically active triiodothyronine and that DIO3 mostly converts triiodothyronine to inactive forms of THs, our results suggest that embryos may modulate maternal signals. TH receptors (THRA and THRB) and a monocarboxylate membrane transporter gene (SLC16A2) were also expressed, enabling TH responses. Our results suggest that altricial embryos may be able to respond to and potentially modulate maternal signals conveyed by THs in early development.

Effect of prenatal glucocorticoids and thyroid hormones on developmental plasticity of mitochondrial aerobic metabolism, growth and survival: an experimental test in wild great tits.

Developmental plasticity is partly mediated by transgenerational effects, including those mediated by the maternal endocrine system. Glucocorticoid and thyroid hormones may play central roles in developmental programming through their action on metabolism and growth. However, the mechanisms by which they affect growth and development remain understudied. One hypothesis is that maternal hormones directly affect the production and availability of energy-carrying molecules (e.g. ATP) by their action on mitochondrial function. To test this hypothesis, we experimentally increased glucocorticoid and thyroid hormones in wild great tit eggs (Parus major) to investigate their impact on offspring mitochondrial aerobic metabolism (measured in blood cells), and subsequent growth and survival. We show that prenatal glucocorticoid supplementation affected offspring cellular aerobic metabolism by decreasing mitochondrial density, maximal mitochondrial respiration and oxidative phosphorylation, while increasing the proportion of the maximum capacity being used under endogenous conditions. Prenatal glucocorticoid supplementation only had mild effects on offspring body mass, size and condition during the rearing period, but led to a sex-specific (females only) decrease in body mass a few months after fledging. Contrary to our expectations, thyroid hormone supplementation did not affect offspring growth or mitochondrial metabolism. Recapture probability as juveniles or adults was not significantly affected by prenatal hormonal treatment. Our results demonstrate that prenatal glucocorticoids can affect post-natal mitochondrial density and aerobic metabolism. The weak effects on growth and apparent survival suggest that nestlings were mostly able to compensate for the transient decrease in mitochondrial aerobic metabolism induced by prenatal glucocorticoids.

Maternally transferred thyroid hormones and life-history variation in birds.

In vertebrates, thyroid hormones (THs) play an important role in the regulation of growth, development, metabolism, photoperiodic responses and migration. Maternally transferred THs are important for normal early phase embryonic development when embryos are not able to produce endogenous THs. Previous studies have shown that variation in maternal THs within the physiological range can influence offspring phenotype. Given the essential functions of maternal THs in development and metabolism, THs may be a mediator of life-history variation across species. We tested the hypothesis that differences in life histories are associated with differences in maternal TH transfer across species. Using birds as a model, we specifically tested whether maternally transferred yolk THs covary with migratory status, developmental mode and traits related to pace-of-life (e.g. basal metabolic rate, maximum life span). We collected un-incubated eggs (n = 1-21 eggs per species, median = 7) from 34 wild and captive bird species across 17 families and six orders to measure yolk THs [both triiodothyronine (T3) and thyroxine (T4)], compiled life-history trait data from the literature and used Bayesian phylogenetic mixed models to test our hypotheses. Our models indicated that both concentrations and total amounts of the two main forms of THs (T3 and T4) were higher in the eggs of migratory species compared to resident species, and total amounts were higher in the eggs of precocial species, which have longer prenatal developmental periods, than in those of altricial species. However, maternal yolk THs did not show clear associations with pace-of-life-related traits, such as fecundity, basal metabolic rate or maximum life span. We quantified interspecific variation in maternal yolk THs in birds, and our findings suggest higher maternal TH transfer is associated with the precocial mode of development and migratory status. Whether maternal THs represent a part of the mechanism underlying the evolution of precocial development and migration or a consequence of such life histories is currently unclear. We therefore encourage further studies to explore the physiological mechanisms and evolutionary processes underlying these patterns.

Association between HSPA5 Promoter Polymorphisms and a Reduced Risk of Normal Tension Glaucoma.

INTRODUCTION: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure (IOP) are likely to play a role in the pathogenesis of optic neuropathy. The potential similarities between Alzheimer's disease (AD) and NTG in cellular apoptosis leading to neurodegeneration have been shown in recent studies. Heat Shock Protein family A member 5 (HSPA5) promoter polymorphisms have been reported to be associated with a risk of AD. The purpose of our study was to investigate the role of HSPA5 promoter polymorphisms in NTG patients. METHODS: A total of 222 patients with NTG, along with 236 normal controls were enrolled in this study. Genomic DNA was amplified through a polymerase chain reaction (PCR) and identified for the polymorphic HSPA5 (-415 and -370) by Xmn1 and BstY1 restriction digestion, respectively. PCR fragments with potential polymorphic HSPA5 (-180) were subjected to sequence-analyses by a Hex-labeled primer. Genotypes for both NTG patients and control groups were compared for statistically significant differences. RESULTS: Polymorphisms (-415) G/A and (-180) del/G were completely linked in our population. The genotype and allele frequency distribution at the -415 G/A and -180 del/G sites showed a significant difference between the NTG cases and controls. The genotype frequency of HSPA5 (-415) AA/(-180) GG and the allele frequency of HSPA5 (-415) A/(-180) G were significantly lower (p = 0.04 and p = 0.01, respectively) in the NTG patients when compared with those in the control group. There was no significant difference in genotype or allele frequency distribution of the HSPA5 (-370) C/T between the NTG and control groups. There was a reduced risk of NTG associated with the carriers for the HSPA5 (-415) A/(-180) G allele compared with that in the control population (p = 0.01). CONCLUSION: HSPA5 (-415) A and (-180) G allele polymorphisms may be protective factors in the development of NTG.

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 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 (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 with 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.

Endocrinology of thermoregulation in birds in a changing climate.

The ability to maintain a (relatively) stable body temperature in a wide range of thermal environments by use of endogenous heat production is a unique feature of endotherms such as birds. Endothermy is acquired and regulated via various endocrine and molecular pathways, and ultimately allows wide aerial, aquatic, and terrestrial distribution in variable environments. However, due to our changing climate, birds are faced with potential new challenges for thermoregulation, such as more frequent extreme weather events, lower predictability of climate, and increasing mean temperature. We provide an overview on thermoregulation in birds and its endocrine and molecular mechanisms, pinpointing gaps in current knowledge and recent developments, focusing especially on non-model species to understand the generality of, and variation in, mechanisms. We highlight plasticity of thermoregulation and underlying endocrine regulation, because thorough understanding of plasticity is key to predicting responses to changing environmental conditions. To this end, we discuss how changing climate is likely to affect avian thermoregulation and associated endocrine traits, and how the interplay between these physiological processes may play a role in facilitating or constraining adaptation to a changing climate. We conclude that while the general patterns of endocrine regulation of thermogenesis are quite well understood, at least in poultry, the molecular and endocrine mechanisms that regulate, e.g. mitochondrial function and plasticity of thermoregulation over different time scales (from transgenerational to daily variation), need to be unveiled. Plasticity may ameliorate climate change effects on thermoregulation to some extent, but the increased frequency of extreme weather events, and associated changes in resource availability, may be beyond the scope and/or speed for plastic responses. This could lead to selection for more tolerant phenotypes, if the underlying physiological traits harbour genetic and individual variation for selection to act on - a key question for future research.

Born to be young? Prenatal thyroid hormones increase early-life telomere length in wild collared flycatchers.

The underlying mechanisms of the lifelong consequences of prenatal environmental condition on health and ageing remain little understood. Thyroid hormones (THs) are important regulators of embryogenesis, transferred from the mother to the embryo. Since prenatal THs can accelerate early-life development, we hypothesized that this might occur at the expense of resource allocation in somatic maintenance processes, leading to premature ageing. Therefore, we investigated the consequences of prenatal TH supplementation on potential hallmarks of ageing in a free-living avian model in which we previously demonstrated that experimentally elevated prenatal TH exposure accelerates early-life growth. Using cross-sectional sampling, we first report that mitochondrial DNA (mtDNA) copy number and telomere length significantly decrease from early-life to late adulthood, thus suggesting that these two molecular markers could be hallmarks of ageing in our wild bird model. Elevated prenatal THs had no effect on mtDNA copy number but counterintuitively 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 might have a role in setting the 'biological' age at birth, but raise questions about the nature of the evolutionary costs of prenatal exposure to high TH levels.

Testing the short-and long-term effects of elevated prenatal exposure to different forms of thyroid hormones.

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 T4 had a higher hatching success compared with control eggs, suggesting conversion of T4 into T3 by the embryo. We detected no evidence for other short-term or long-term effects of yolk THs. These results suggest that yolk THs are important in the embryonic stage of precocial birds, but other short- and long-term consequences remain unclear. Research on maternal THs 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.

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 and offspring 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 biologically active triiodothyronine, T3) during egg laying using T4 implants in females of a wild population of pied flycatchers (Ficedula hypoleuca), and measured the resulting plasma and yolk T4 and T3 levels. We found an increase in plasma and yolk T4 and no change in plasma or yolk T3 concentration, leading to a decrease in yolk T3/T4 ratio in response to the T4 treatment. The yolk T3/T4 ratio was similar to the plasma ratio in females during the yolking phase. This suggests that mothers are not able to regulate TH transfer to yolk but may regulate the T4 to T3 conversion to avoid potential costs of elevated exposure to the active hormone to herself and to her progeny. The absence of regulation in hormone transfer to eggs is in contrast to our predictions. Future studies on deiodinase activity that converts T4 to T3 in maternal and embryonic tissues may help our understanding of how mothers regulate circulating THs during breeding, as well as the embryos' role in converting maternal T4 to its biologically active T3 form during development.

Testing for context-dependent effects of prenatal thyroid hormones on offspring survival and physiology: an experimental temperature manipulation.

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 differential effects of hormones under different environmental contexts. 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.

Manipulation of Prenatal Thyroid Hormones Does Not Affect Growth or Physiology in Nestling Pied Flycatchers.

Hormones transferred from mothers to their offspring are thought to be a tool for mothers to prepare their progeny for expected environmental conditions, thus increasing fitness. Thyroid hormones (THs) are crucial across vertebrates for embryonic and postnatal development and metabolism. Yet yolk THs have mostly been ignored in the context of hormone-mediated maternal effects. In addition, the few studies on maternal THs have yielded contrasting results that could be attributed to either species or environmental differences. In this study, we experimentally elevated yolk THs (within the natural range) in a wild population of a migratory passerine, the European pied flycatcher (Ficedula hypoleuca), and assessed the effects on hatching success, nestling survival, growth, and oxidative status (lipid peroxidation, antioxidant enzyme activity, and oxidative balance). We also sought to compare our results with those of a closely related species, the collared flycatcher (Ficedula albicolis), that has strong ecological and life-history similarities with our species. We found no effects of yolk THs on any of the responses measured. We could detect only a weak trend on growth: elevated yolk THs tended to increase growth during the second week after hatching. Our results contradict the findings of previous studies, including those of the collared flycatcher. However, differences in fledging success and nestling growth between both species in the same year suggest a context-dependent influence of the treatment. This study should stimulate more research on maternal effects mediated by THs and their potential context-dependent effects.

MEK2 is a critical modulating mechanism to down-regulate GCIP stability and function in cancer cells.

Loss of tumor suppressor activity and upregulation of oncogenic pathways simultaneously contribute to tumorigenesis. Expression of the tumor suppressor, GCIP (Grap2- and cyclin D1-interacting protein), is usually reduced or lost in advanced cancers, as seen in both mouse tumor models and human cancer patients. However, no previous study has examined how cancer cells down-regulate GCIP expression. In this study, we first validate the tumor suppressive function of GCIP using clinical gastric cancer tissues and online database analysis. We then reveal a novel mechanism whereby MEK2 directly interacts with and phosphorylates GCIP at its Ser313 and Ser356 residues to promote the turnover of GCIP by ubiquitin-mediated proteasomal degradation. We also reveal that decreased GCIP stability enhances cell proliferation and promotes cancer cell migration and invasion. Taken together, these findings provide a more comprehensive view of GCIP in tumorigenesis and suggest that the oncogenic MEK/ERK signaling pathway negatively regulates the protein level of GCIP to promote cell proliferation and migration.

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) downregulation 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.

Between- and Within-Individual Variation of Maternal Thyroid Hormone Deposition in Wild Great Tits (Parus major).

Maternal hormones are often considered a mediator of anticipatory maternal effects; namely, mothers adjust maternal hormone transfer to prepare the offspring for the anticipated environment. The flexibility for mothers to adjust hormone transfer is therefore a prerequisite for such anticipatory maternal effects. Nevertheless, previous studies have focused only on the average differences of maternal hormone transfer between groups and neglected the substantial individual variation, despite the fact that individual plasticity in maternal hormone transfer is actually the central assumption. In this study, we studied the between- and within-individual variation of maternal thyroid hormones (THs) in egg yolk of wild great tits (Parus major) and estimated the individual plasticity of maternal yolk THs across environmental temperature, clutch initiation dates, and egg laying order using linear mixed effects models. Interestingly, our models provide statistical evidence that the two main THs-the main biologically active hormone T3 and T4, which is mostly considered a prohormone-exhibited different variation patterns. Yolk T3 showed significant between-individual variation on the average levels, in line with its previously reported moderate heritability. Yolk T4, however, showed significant between-clutch variation in the pattern over the laying sequence, suggesting a great within-individual plasticity. Our findings suggest that the role and function of the hormone within the endocrine axis likely influences its flexibility to respond to environmental change. Whether the flexibility of T4 deposition brings a fitness advantage should be examined along with its potential effects on offspring, which remain to be further investigated.