Dietary fatty acids modulate oxidative stress response to air pollution but not to infection.

Anthropogenic changes to the environment expose wildlife to many pollutants. Among these, tropospheric ozone is of global concern and a highly potent pro-oxidant. In addition, human activities include several other implications for wildlife, e.g., changed food availability and changed distribution of pathogens in cities. These co-occurring habitat changes may interact, thereby modulating the physiological responses and costs related to anthropogenic change. For instance, many food items associated with humans (e.g., food waste and feeders for wild birds) contain relatively more ω6-than ω3-polyunsaturated fatty acids (PUFAs). Metabolites derived from ω6-PUFAs can enhance inflammation and oxidative stress towards a stimulus, whereas the opposite response is linked to ω3-derived metabolites. Hence, we hypothesized that differential intake of ω6-and ω3-PUFAs modulates the oxidative stress state of birds and thereby affects the responses towards pro-oxidants. To test this, we manipulated dietary ω6:ω3 ratios and ozone levels in a full-factorial experiment using captive zebra finches (Taeniopygia guttata). Additionally, we simulated an infection, thereby also triggering the immune system's adaptive pro-oxidant release (i.e., oxidative burst), by injecting lipopolysaccharide. Under normal air conditions, the ω3-diet birds had a lower antioxidant ratio (GSH/GSSG ratio) compared to the ω6-diet birds. When exposed to ozone, however, the diet effect disappeared. Instead, ozone exposure overall reduced the total concentration of the key antioxidant glutathione (tGSH). Moreover, the birds on the ω6-rich diet had an overall higher antioxidant capacity (OXY) compared to birds fed a ω3-rich diet. Interestingly, only the immune challenge increased oxidative damage, suggesting the oxidative burst of the immune system overrides the other pro-oxidative processes, including diet. Taken together, our results show that ozone, dietary PUFAs, and infection all affect the redox-system, but in different ways, suggesting that the underlying responses are decoupled despite that they all increase pro-oxidant exposure or generation. Despite lack of apparent cumulative effect in the independent biomarkers, the combined single effects could together reduce overall cellular functioning and efficiency over time in wild birds exposed to pathogens, ozone, and anthropogenic food sources.

Quantifying the influence of urban biotic and abiotic environmental factors on great tit nestling physiology.

There is a long history of avian studies investigating the impacts of urbanization. While differences in several life-history traits have been documented, either between urban and rural populations or across generalized urbanization gradients, a detailed understanding of which specific environmental variables cause these phenotypic differences is still lacking. Here, we quantified several local environmental variables coupled to urbanization (air pollution, tree composition, ambient temperature, and artificial light at night [ALAN]) within territories of breeding great tits (Parus major). We linked the environmental variables to physiological measures of the nestlings (circulating fatty acid composition [FA], antioxidant capacity and an oxidative damage marker [malondialdehyde; MDA]), to garner a mechanistic understanding of the impact of urbanization. We found that the antioxidant capacity of nestlings decreased with higher numbers of oak trees and levels of PM2.5 (airborne particulate matter with a diameter < 2.5 µm). Furthermore, the ratio of ω6:ω3 polyunsaturated FAs, important for immune function, was positively correlated with PM2.5 concentration, while being negatively associated with ambient temperature and number of non-native trees in the territory. Body mass and wing length both increased with the number of local oak trees. We also show, through a principal component analysis, that while the environmental variables fall into an urbanization gradient, this gradient is insufficient to explain the observed physiological responses. Therefore, accounting for individual environmental variables in parallel, and thus allowing for interactions between these, is crucial to fully understand the urban ecosystem.

Exposure to artificial light at night alters innate immune response in wild great tit nestlings.

The large-scale impact of urbanization on wildlife is rather well documented; however, the mechanisms underlying the effects of urban environments on animal physiology and behaviour are still poorly understood. Here, we focused on one major urban pollutant - artificial light at night (ALAN) - and its effects on the capacity to mount an innate immune response in wild great tit (Parus major) nestlings. Exposure to ALAN alters circadian rhythms of physiological processes, by disrupting the nocturnal production of the hormone melatonin. Nestlings were exposed to a light source emitting 3 lx for seven consecutive nights. Subsequently, nestlings were immune challenged with a lipopolysaccharide injection, and we measured haptoglobin and nitric oxide levels pre- and post-injection. Both haptoglobin and nitric oxide are important markers for innate immune function. We found that ALAN exposure altered the innate immune response, with nestlings exposed to ALAN having lower haptoglobin and higher nitric oxide levels after the immune challenge compared with dark-night nestlings. Unexpectedly, nitric oxide levels were overall lower after the immune challenge than before. These effects were probably mediated by melatonin, as ALAN-treated birds had on average 49% lower melatonin levels than the dark-night birds. ALAN exposure did not have any clear effects on nestling growth. This study provides a potential physiological mechanism underlying the documented differences in immune function between urban and rural birds observed in other studies. Moreover, it gives evidence that ALAN exposure affects nestling physiology, potentially causing long-term effects on physiology and behaviour, which ultimately can affect their fitness.

In ovo yolk carotenoid and testosterone levels interactively influence female transfer of yolk antioxidants to her eggs.

Mothers can influence prenatal conditions by varying the amount of nutrients, hormones or antioxidants they provide to their developing young. Some of these substances even affect the transfer of these compounds in the next generation, but it is less clear how different maternally transmitted compounds interact with each other to shape reproductive resource allocation in their offspring. Here, we found that female Japanese quails (Coturnix japonica) that were exposed to high carotenoid levels during embryonic development transferred lower concentrations of yolk antioxidants to their own eggs later in life. This effect disappeared when both testosterone and carotenoid concentrations were manipulated simultaneously, showing long-term and interactive effects of these maternally derived egg components on a female's own egg composition. Given that exposure to high levels of testosterone during embryo development stimulates the production of reactive oxygen species (ROS) and impairs antioxidant defenses, we propose that carotenoids act as in ovo antioxidants in an oxidatively stressful environment (i.e. when levels of testosterone are high) but might have prooxidant properties in an environment where they are not used to counteract an increased production of ROS. In line with this hypothesis, we previously showed that prenatal exposure to increased concentrations of yolk carotenoids leads to a rise of oxidative damage at adulthood, but only when yolk testosterone concentrations were not experimentally increased as well. As a consequence, antioxidants in the body may be used to limit oxidative damage in females exposed to high levels of carotenoids during development (but not in females exposed to increased levels of both carotenoids and testosterone), resulting in lower amounts of antioxidants being available for deposition into eggs. Since prenatal antioxidant exposure is known to influence fitness-related traits, the effect detected in this study might have transgenerational consequences.

High Yolk Testosterone Transfer Is Associated with an Increased Female Metabolic Rate.

Yolk androgens of maternal origin are important mediators of prenatal maternal effects. Although in many species short-term benefits of exposure to high yolk androgen concentrations for the offspring have been observed, females differ substantially in the amount of androgens they transfer to their eggs. It suggests that costs for the offspring or the mother constrain the evolution of maternal hormone transfer. However, to date, the nature of these costs remains poorly understood. Unlike most previous work that focused on potential costs for the offspring, we here investigated whether high yolk testosterone transfer is associated with metabolic costs (i.e., a higher metabolic rate) for the mother. We show that Japanese quail (Coturnix japonica) females that deposit higher testosterone concentrations into their eggs have a higher resting metabolic rate. Because a higher metabolic rate is often associated with a shorter life span, this relationship may explain the negative association between yolk testosterone transfer and female longevity observed in the wild. Our results suggest that metabolic costs for the mother can balance the short-term benefits of yolk testosterone exposure for the offspring, thereby contributing to the maintenance of variation in maternal yolk hormone transfer in natural populations.

Matrilineal inheritance of a key mediator of prenatal maternal effects.

Sex-linkage is predicted to evolve in response to sex-specific or sexually antagonistic selection. In line with this prediction, most sex-linked genes are associated with reproduction in the respective sex. In addition to traits directly involved in fertility and fecundity, mediators of maternal effects may be predisposed to evolve sex-linkage, because they indirectly affect female fitness through their effect on offspring phenotype. Here, we test for sex-linked inheritance of a key mediator of prenatal maternal effects in oviparous species, the transfer of maternally derived testosterone to the eggs. Consistent with maternal inheritance, we found that in Japanese quail (Coturnix japonica) granddaughters resemble their maternal (but not their paternal) grandmother in yolk testosterone deposition. This pattern of resemblance was not due to non-genetic priming effects of testosterone exposure during prenatal development, as an experimental manipulation of yolk testosterone levels did not affect the females' testosterone transfer to their own eggs later in life. Instead, W chromosome and/or mitochondrial variation may underlie the observed matrilineal inheritance pattern. Ultimately, the inheritance of mediators of maternal effects along the maternal line will allow for a fast and direct response to female-specific selection, thereby affecting the dynamics of evolutionary processes mediated by maternal effects.

Artificial selection reveals the energetic expense of producing larger eggs.

BACKGROUND: The amount of resources provided by the mother before birth has important and long-lasting effects on offspring fitness. Despite this, there is a large amount of variation in maternal investment seen in natural populations. Life-history theory predicts that this variation is maintained through a trade-off between the benefits of high maternal investment for the offspring and the costs of high investment for the mother. However, the proximate mechanisms underlying these costs of reproduction are not well understood. Here we used artificial selection for high and low maternal egg investment in a precocial bird, the Japanese quail (Coturnix japonica) to quantify costs of maternal reproductive investment. RESULTS: We show that females from the high maternal investment lines had significantly larger reproductive organs, which explained their overall larger body mass, and resulted in a higher resting metabolic rate (RMR). Contrary to our expectations, this increase in metabolic activity did not lead to a higher level of oxidative damage. CONCLUSIONS: This study is the first to provide experimental evidence for metabolic costs of increased per offspring investment.

Long-term effect of yolk carotenoid levels on testis size in a precocial bird.

Conditions experienced during prenatal development can have long-lasting organizational effects on offspring. Maternal carotenoids deposited in the eggs of birds and other oviparous species play an important role during fast embryonic growth and chick development through their antioxidant properties. However, the long-term consequences of variation in maternal carotenoid transfer for the offspring have seldom been considered. Since plasma carotenoid levels at adulthood are known to influence testis size and yolk carotenoid levels influence the ability to extract carotenoids later in life, we hypothesized that maternally transmitted carotenoids might influence gonad size at adulthood. Here, we showed that male Japanese quail (Coturnix japonica) originating from a carotenoid-enriched egg had smaller testes than control individuals at adulthood. This result shows that yolk carotenoids have long-term organizational effects. In addition, given that carotenoid intake at sexual maturity increases sperm quality and that a decreased testis size is associated with a lower sperm production, we propose that carotenoid exposure during embryo development might influence a trade-off between ejaculate size and sperm quality.

Predictors of blood pressure response: Obesity is associated with a less pronounced treatment response after renal denervation.

OBJECTIVES: The purpose of this study was to identify predictors of BP response. BACKGROUND: Catheter-based renal denervation (RDN) causes significant blood pressure (BP) reductions in a large number of patients with resistant hypertension. METHODS: One hundred one consecutive patients with resistant hypertension who underwent RDN with the Symplicity™ catheter were included in this retrospective study. Primary endpoint was the change in office systolic BP after 6 months. Uni- and multivariate logistic regression analyses were performed to detect baseline predictors of a significant BP response 6 months after RDN (age, gender, office and ambulatory BP, renal function, body mass index [BMI], diabetes mellitus, antihypertensive medication, number of ablations). RESULTS: The procedure was technically uneventful in all patients. Mean BP at baseline was 166.6/90.2 ± 22.5/16.4 mmHg and decreased by -14.7 (P < 0.0001)/-5.3 (P < 0.001) ± 22.8/14.1 mm Hg at 6-month follow-up. Similarly, paired analysis of 24-hr-ambulatory BP measurement (n = 71) showed a significant reduction of mean systolic BP by 6.8 ± 14.4 mm Hg (P < 0.0002). Upon univariate analyses, a higher baseline office systolic BP (P < 0.0001) and lower BMI (P = 0.014) were identified as significant predictors of the magnitude of BP response after 6 months. Importantly, on multivariate analysis, baseline office systolic BP (standardized ß = -0.46; r = -0.47; P < 0.0001) and BMI (standardized ß = 0.21; r = 0.95; P = 0.019) remained significant. CONCLUSION: Blood pressure reductions after RDN were more pronounced in patients with higher baseline blood pressure and lower BMI. These findings may have implications regarding patient selection for renal denervation. © 2015 Wiley Periodicals, Inc.

Efficacy and safety of renal denervation in elderly patients with resistant hypertension.

BACKGROUND: Catheter-based renal sympathetic denervation (RD) causes significant blood pressure (BP) reductions in patients with resistant hypertension (rHTN). However, hypertensive elderly patients reportedly have a lower sympathetic tone than younger patients and a BP lowering effect of RD in this population has not yet been demonstrated. The purpose of this study was to assess the efficacy and safety of RD in elderly patients. METHODS: We reviewed all consecutive patients aged ≥ 75 years (mean: 78 years) with rHTN treated with RD. Twenty-four patients were included in this prospective study. Office and ambulatory BPs were assessed at baseline and 6-months follow-up. Primary endpoint was the change in office systolic BP at 6 months. RESULTS: Baseline mean office BP was 173/86 ± 21/13 mm Hg. Baseline 24-hr mean ambulatory BP, available in 22 patients, was 158/80 ± 20/13 mm Hg. Baseline creatinine was 1.0 ± 0.18 mg/dl and mean number of antihypertensive agents at baseline 4.3 ± 1.4. No device- or procedure-related adverse events occurred. At 6-months follow-up, the mean office BP decreased by 19/11 ± 29/16 mm Hg (P < 0.01 compared to baseline). Mean systolic 24 hr ambulatory BP, available in 17 patients, decreased by 9/5 ± 13/13 mm Hg. Antihypertensive medications could be reduced in nine patients. Furthermore, renal function was not impaired. CONCLUSION: According to our findings, a similar magnitude of BP reduction as reported in previous trials can be expected in elderly patients. Elderly patients with rHTN should not be excluded from renal denervation.

Renal denervation in a patient with prior renal artery stenting.

This is a case report of a 69-year-old female with treatment-resistant severe arterial hypertension despite prior successful percutaneous intervention to both renal arteries for significant renal artery stenoses (stenting of the right and balloon angioplasty of the left renal artery). The office blood pressure was 221/108 mm Hg at baseline. Secondary hypertension was ruled out and catheter-based renal denervation performed (distal to the stent in the right renal artery and in the usual fashion in the left renal artery) without complications. The office blood pressure decreased at 1- and 3-month follow-up to 185/93 mm Hg and 182/95 mm Hg, respectively. This case illustrates the feasibility and potential efficacy of catheter-based renal denervation in patients with a renal artery stent, an important finding as persistent hypertension is common in patients despite successful renal artery stenting and currently available trials examining renal denervation have excluded patients with prior renal artery stents.