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.

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.

Loss of the Vitamin B-12 Transport Protein Tcn2 Results in Maternally Inherited Growth and Developmental Defects in Zebrafish.

BACKGROUND: In humans, vitamin B-12 (cobalamin) transport involves 3 paralogous proteins: transcobalamin, haptocorrin, and intrinsic factor. Zebrafish (Danio rerio) express 3 genes that encode proteins homologous to known B-12 carrier proteins: tcn2 (a transcobalamin ortholog) and 2 atypical ß-domain-only homologs, tcnba and tcnbb. OBJECTIVES: Given the orthologous relation between zebrafish Tcn2 and human transcobalamin, we hypothesized that zebrafish carrying null mutations of tcn2 would exhibit phenotypes consistent with vitamin B-12 deficiency. METHODS: First-generation and second-generation tcn2-/- zebrafish were characterized using phenotypic assessments, metabolic analyses, viability studies, and transcriptomics. RESULTS: Homozygous tcn2-/- fish produced from a heterozygous cross are viable and fertile but exhibit reduced growth, which persists into adulthood. When first-generation female tcn2-/- fish are bred, their offspring exhibit gross developmental and metabolic defects. These phenotypes are observed in all offspring from a tcn2-/- female regardless of the genotype of the male mating partner, suggesting a maternal effect, and can be rescued with vitamin B-12 supplementation. Transcriptome analyses indicate that offspring from a tcn2-/- female exhibit expression profiles distinct from those of offspring from a tcn2+/+ female, which demonstrate dysregulation of visual perception, fatty acid metabolism, and neurotransmitter signaling pathways. CONCLUSIONS: Our findings suggest that the deposition of vitamin B-12 in the yolk by tcn2-/- females may be insufficient to support the early development of their offspring. These data present a compelling model to study the effects of vitamin B-12 deficiency on early development, with a particular emphasis on transgenerational effects and gene-environment interactions.

Impact of mothers' early life exposure to low or high folate on progeny outcome and DNA methylation patterns.

The dynamic patterning of DNA and histone methylation during oocyte development presents a potentially susceptible time for epigenetic disruption due to early life environmental exposure of future mothers. We investigated whether maternal exposure to folic acid deficient and supplemented diets starting in utero could affect oocytes and cause adverse developmental and epigenetic effects in next generation progeny. Female BALB/c mice (F0) were placed on one of four amino acid defined diets for 4 weeks before pregnancy and throughout gestation and lactation: folic acid control (rodent recommended daily intake; Ctrl), 7-fold folic acid deficient, 10-fold folic acid supplemented or 20-fold folic acid supplemented diets. F1 female pups were weaned onto Ctrl diets, mated to produce the F2 generation and the F2 offspring were examined at E18.5 for developmental and epigenetic abnormalities. Resorption rates were increased and litter sizes decreased amongst F2 E18.5-day litters in the 20-fold folic acid supplemented group. Increases in abnormal embryo outcomes were observed in all three folic acid deficient and supplemented groups. Subtle genome-wide DNA methylation alterations were found in the placentas and brains of F2 offspring in the 7-fold folic acid deficient , 10-fold folic acid supplemented and 20-fold folic acid supplemented groups; in contrast, global and imprinted gene methylation were not affected. The findings show that early life female environmental exposures to both low and high folate prior to oocyte maturation can compromise oocyte quality, adversely affecting offspring of the next generation, in part by altering DNA methylation patterns.

Parental transgenerational epigenetic inheritance related to dietary crude oil exposure in Danio rerio.

Transgenerational inheritance from both parental lines can occur by genetic and epigenetic inheritance. Maternal effects substantially influence offspring survival and fitness. However, investigation of the paternal contribution to offspring success has been somewhat neglected. In the present study, adult zebrafish were separated into female and male groups exposed for 21 days to either a control diet or to a diet containing water accommodated fractions of crude oil. Four F1 offspring groups were obtained: (1) control (non-exposed parents), (2) paternally exposed, (3) maternally exposed and (4) dual-parent-exposed. To determine the maternal and paternal influence on their offspring, we evaluated responses from molecular to whole organismal levels in both generations. Growth rate, hypoxia resistance and heart rate did not differ among parental groups. However, global DNA methylation in heart tissue was decreased in oil-exposed fish compared with control parents. This decrease was accompanied by an upregulation of glycine N-methyltransferase. Unexpectedly, maternal, paternal and dual exposure all enhanced survival of F1 offspring raised in oiled conditions. Regardless of parental exposure, however, F1 offspring exposed to oil exhibited bradycardia. Compared with offspring from control parents, global DNA methylation was decreased in the three offspring groups derived from oil-exposed parents. However, no difference between groups was observed in gene regulation involved in methylation transfer, suggesting that the changes observed in the F1 populations may have been inherited from both parental lines. Phenotypic responses during exposure to persistent environmental stressors in F1 offspring appear to be influenced by maternal and paternal exposure, potentially benefitting offspring populations to survive in challenging environments.

Dietary carotenoid supplementation facilitates egg laying in a wild passerine.

During egg laying, females face a trade-off between self-maintenance and investment into current reproduction, since providing eggs with resources is energetically demanding, in particular if females lay one egg per day. However, the costs of egg laying not only relate to energetic requirements, but also depend on the availability of specific resources that are vital for egg production and embryonic development. One of these compounds are carotenoids, pigments with immuno-stimulatory properties, which are crucial during embryonic development. In this study, we explore how carotenoid availability alleviates this trade-off and facilitates egg laying in a small bird species, the blue tit (Cyanistes caeruleus). Blue tits have among the largest clutch size of all European passerines and they usually lay one egg per day, although laying interruptions are frequent. We performed a lutein supplementation experiment and measured potential consequences for egg laying capacity and egg quality. We found that lutein-supplemented females had less laying interruptions and thus completed their clutch faster than control females. No effects of treatment were found on the onset of egg laying or clutch size. Experimentally enhanced carotenoid availability did not elevate yolk carotenoid levels or egg mass, but negatively affected eggshell thickness. Our results provide hence evidence on the limiting role of carotenoids during egg laying. However, the benefits of laying faster following lutein supplementation were counterbalanced by a lower accumulation of calcium in the eggshell. Thus, even though single components may constrain egg laying, it is the combined availability of a range of different resources which ultimately determines egg quality and thus embryonic development.

Transgenerational impacts of herbivory and inbreeding on reproductive output in Solanum carolinense.

PREMISE: Plant maternal effects on offspring phenotypes are well documented. However, little is known about how herbivory on maternal plants affects offspring fitness. Furthermore, while inbreeding is known to reduce plant reproductive output, previous studies have not explored whether and how such effects may extend across generations. Here, we addressed the transgenerational consequences of herbivory and maternal plant inbreeding on the reproduction of Solanum carolinense offspring. METHODS: Manduca sexta caterpillars were used to inflict weekly damage on inbred and outbred S. carolinense maternal plants. Cross-pollinations were performed by hand to produce seed from herbivore-damaged outbred plants, herbivore-damaged inbred plants, undamaged outbred plants, and undamaged inbred plants. The resulting seeds were grown in the greenhouse to assess emergence rate and flower production in the absence of herbivores. We also grew offspring in the field to examine reproductive output under natural conditions. RESULTS: We found transgenerational effects of herbivory and maternal plant inbreeding on seedling emergence and reproductive output. Offspring of herbivore-damaged plants had greater emergence, flowered earlier, and produced more flowers and seeds than offspring of undamaged plants. Offspring of outbred maternal plants also had greater seedling emergence and reproductive output than offspring of inbred maternal plants, even though all offspring were outbred. Moreover, the effects of maternal plant inbreeding were more severe when plant offspring were grown in field conditions. CONCLUSIONS: This study demonstrates that both herbivory and inbreeding have fitness consequences that extend across generations even in outbred progeny.

Transgenerational disrupting impacts of atrazine in zebrafish: Beneficial effects of dietary spirulina.

In a range of fish species, offspring sustainability is much dependent to their mother's investment into the egg yolk. A healthy environment helps broodfish to produce normal quality offspring. However, deviation from optimal conditions can disturb body functions that effect the next generation. Here, zebrafish (Danio rerio) was employed to investigate the transgenerational impacts of an immunotoxic and endocrine disruptor, atrazine (AZ). In addition, the possible ameliorated effects of a nutraceutical, Arthrospira platensis (spirulina- SP), was considered. Adult females were either exposed to 0 (Cn), 5 (AZ5), and 50 (AZ50) µg/L AZ or fed SP-supplemented diet (10 g/kg; SP). In combination treatments, fish were also exposed to AZ and fed SP (SP-AZ5 and SP-AZ50). Embryos were obtained after 28 d of exposure. Exposure to AZ50 caused females to produce eggs with significantly lower fertilization and hatching. No changes were observed in the concentrations of thyroid hormones. AZ significantly increased cortisol response and reduced levels of immunoglobulin, lysozyme and complement activities in females and their offspring. SP-AZ5 and SP-AZ50 females, however, resisted to the toxic effects of AZ, produced embryos with lower cortisol content and higher immunity competence. Bactericidal activity of the embryos also showed the transgenerational antimicrobial effects of SP along with the AZ immunotoxicity. Overall, these results indicate that AZ could have long lasting toxic effects on fish, and that dietary SP-supplementation could ameliorate AZ induced transgenerational toxic effects.

Effects of l-carnitine in the distillers dried grains with solubles diet of sows on reproductive performance and antioxidant status of sows and their offspring.

Distillers dried grains with solubles (DDGS) are highly susceptible to lipid oxidation because DDGS contain about 10% crude fat, which is largely composed of polyunsaturated fatty acids. l-carnitine serves an important function in fatty acids ß-oxidation, and also has antioxidant properties. The objective of this study was to examine the effects of l-carnitine in the DDGS diet of gestating and lactating sows on reproductive performance, milk composition and antioxidant status of sows and their offspring. One hundred and twenty sows (Landrace×Large white, mean parity 4.2, initial BW 230 kg) were randomly allotted to 1 of 4 dietary treatments (n=30 sows/treatment). Treatments were arranged as a 2×2 factorial with two levels of dietary DDGS (0 v. 250 g/kg in gestating diets and 400 g/kg in lactating diets) and two levels of dietary l-carnitine (0 v. 100 mg/kg in gestating diets and 0 v. 200 mg/kg in lactating diets). Distillers dried grains with solubles had no significant effect on litter size but significantly reduced the birth weights and weaning weights of piglets (P0.05). Supplementing the diets with l-carnitine had no significant effect of total litter size (P>0.05) but increased the number of piglets born alive and piglets weaned, birth weight and weaning weight of piglets and litter weight at birth and weaning (P<0.05). l-carnitine supplementation also increased the concentration of l-carnitine in milk and l-carnitine status of piglets (P<0.05). The antioxidant enzyme activities of new born and weaning piglets were increased (P<0.05) by maternal dietary l-carnitine but this did not extend to finishing pigs. In conclusion, including DDGS in the sows diet could induce oxidative stress, which may be associated with the reduced individual birth and weaning weight of piglets. Dietary l-carnitine supplementation improved the antioxidant and l-carnitine status of sows, which may be associated with the improved reproduction and piglet performance and the antioxidant status of piglets at birth and weaning. There were no interactions between DDGS and l-carnitine.

Yolk vitamin E positively affects prenatal growth but not oxidative status in yellow-legged gull embryos.

Parental effects occur whenever the phenotype of parents or the environment that they experience influences the phenotype and fitness of their offspring. In birds, parental effects are often mediated by the size and biochemical quality of the eggs in terms of maternally transferred components. Exogenous antioxidants are key egg components that accomplish crucial physiological functions during early life. Among these, vitamin E plays a vital role during prenatal development when the intense metabolism accompanying rapid embryo growth results in overproduction of pro-oxidant molecules. Studies of captive birds have demonstrated the positive effect of vitamin E supplementation on diverse phenotypic traits of hatchling and adult individuals, but its effects on embryo phenotype has never been investigated neither in captivity nor under a natural selection regime. In the present study, we experimentally tested the effect of the in ovo supplementation of vitamin E on morphological traits and oxidative status of yellow-legged gull (Larus michahellis) embryos. The supplementation of vitamin E promoted somatic growth in embryos soon before hatching, but did not affect their oxidative status. Our results suggest that maternally transferred vitamin E concentrations are optimized to prevent imbalances of oxidative status and the consequent raise of oxidative damage in yellow-legged gull embryos during prenatal development.

Development of food intake controls: neuroendocrine and environmental regulation of food intake during early life.

This article is part of a Special Issue "Energy Balance". The development of neuroendocrine regulation of food intake during early life has been shaped by natural selection to allow for optimal growth and development rates needed for survival. In vertebrates, neonates or early larval forms typically exhibit "feeding drive," characterized by a developmental delay in 1) responsiveness of the hypothalamus to satiety signals (e.g., leptin, melanocortins) and 2) sensitivity to environmental cues that suppress food intake. Homeostatic regulation of food intake develops once offspring transition to later life history stages when growth is slower, neuroendocrine systems are more mature, and appetite becomes more sensitive to environmental or social cues. Across vertebrate groups, there is a tremendous amount of developmental plasticity in both food intake regulation and stress responsiveness depending on the environmental conditions experienced during early life history stages or by pregnant/brooding mothers. This plasticity is mediated through the organizing effects of hormones acting on the food intake centers of the hypothalamus during development, which alter epigenetic expression of genes associated with ingestive behaviors. Research is still needed to reveal the mechanisms through which environmental conditions during development generate and maintain these epigenetic modifications within the lifespan or across generations. Furthermore, more research is needed to determine whether observed patterns of plasticity are adaptive or pathological. It is clear, however, that developmental programming of food intake has important effects on fitness, and therefore, has ecological and evolutionary implications.

Maternal genotype influences behavioral development of 3×Tg-AD mouse pups.

Transgenic mice are a valuable tool in the investigation of neurodegenerative disorders such as Alzheimer's disease. The triple transgenic mouse (3×Tg-AD) is a model of Alzheimer's disease that possesses age-related amyloid beta plaques, neurofibrillary tangles and cell death as well as cognitive decline. Because maternal effects may interact with pup genotype in determining behavior phenotypes, we used a cross-fostering paradigm to investigate the effects of maternal genotype on behavioral development of the 3×Tg-AD mouse model and its wildtype control (B6129S1F2) from 2 to 24 days of age. Developmental patterns of behavior were influenced by both pup and maternal genotype. The 3×Tg-AD mice were delayed in sensory reflexes, showed less activity and poorer habituation to a novel object, but showed advanced development of motor reflexes compared to wildtype pups. While there were no differences in levels of maternal care between transgenic and control mothers, maternal genotype affected the development of several pup reflexes (body weight, hindlimb grasp reflex, loss of crossed extensor reflex, vibrissae response, righting reflex) and the number of horizontal and vertical beam breaks in an open field. This study is the first to examine neurobehavioral development and maternal behavior in a mouse model of Alzheimer's disease, and highlights the importance of investigating the consequences of early environmental experience as well as genetic manipulation on behavioral development.