Paternal care in a fish: epigenetics and fitness enhancing effects on offspring anxiety

In many animals, including humans, interactions with caring parents can have long-lasting effects on offspring sensitivity to stressors. However, whether these parental effects impact offspring fitness in nature is often unclear. In addition, despite evidence that maternal care can influence offspring behaviour via epigenetic alterations to the genome, it remains unclear whether paternal care has similar effects. Here, we show in three-spined sticklebacks, a fish in which fathers are the sole provider of offspring care, that the direct care provided by fathers affects offspring anxiety and the potential for epigenetic alterations to the offspring genome. We find that families are differentially vulnerable to early stress and fathers can compensate for this differential sensitivity with the quality of their care. This variation in paternal care is also linked to the expression in offspring brains of a DNA methyltransferase (Dnmt3a) responsible for de novo methylation. We show that these paternal effects are potentially adaptive and anxious offspring are unlikely to survive an encounter with a predator. By supplying offspring care, fathers reduce offspring anxiety thereby increasing the survival of their offspring—not in the traditional sense through resource provisioning but through an epigenetic effect on offspring behavioural development.     

Paternal Effects on Offspring Fitness Reflect Father’s Social Environment

In many species, males influence phenotypic traits in their offspring through non-genetic paternal effects. Such effects can represent a form of paternal investment, and males may benefit by adjusting the effects depending on environmental parameters, such as operational sex ratio, so as to maximize offspring fitness. In the neriid fly Telostylinus angusticollis, fathers reared on a nutrient-rich larval diet produce larger offspring, independent of the rearing environment of the offspring. Here we asked whether this paternal effect was influenced by the social environment to which fathers were exposed. We found significant interactions of the effects of paternal larval diet quality and social environment (same-sex vs. mixed-sex groups) on offspring fitness-related traits. Fathers reared on a nutrient-rich diet produced larger male offspring when housed in mixed-sex groups. However, fathers reared on a nutrient-rich diet produced more viable offspring (or more viable sperm) when housed in same-sex groups prior to mating. These results suggest that fitness-enhancing paternal effects can trade off, consistent with parental investment theory on the offspring size-number trade-off, which suggests that these traits represent alternative investment options and parents are selected to optimize the balance based on a range of environmental variables. This is the first study to show that males can facultatively modulate paternal effects based on the social environment.     

Maternal and paternal condition effects on offspring phenotype in Telostylinus angusticollis (Diptera: Neriidae)

It is widely recognized that maternal phenotype can have important effects on offspring, but paternal phenotype is generally assumed to have no influence in animals lacking paternal care. Nonetheless, selection may favour the transfer of environmentally acquired condition to offspring from both parents. Using a split-brood, cross-generational laboratory design, we manipulated a key environmental determinant of condition - larval diet quality - of parents and their offspring in the fly Telostylinus angusticollis, in which there is no evidence of paternal provisioning. Parental diet did not affect offspring survival, but high-condition mothers produced larger eggs, and their offspring developed more rapidly when on a poor larval diet. Maternal condition had no effect on adult body size of offspring. By contrast, large, high-condition fathers produced larger offspring, and follow-up assays showed that this paternal effect can be sufficient to increase mating success of male offspring and fecundity of female offspring. Our findings suggest that both mothers and fathers transfer their condition to offspring, but with effects on different offspring traits. Moreover, our results suggest that paternal effects can be important even in species lacking conventional forms of paternal care. In such species, the transfer of paternal condition to offspring could contribute to indirect selection on female mate preferences.     

Advancing Paternal Age Is Associated with Deficits in Social and Exploratory Behaviors in the Offspring: A Mouse Model

Background

Accumulating evidence from epidemiological research has demonstrated an association between advanced paternal age and risk for several psychiatric disorders including autism, schizophrenia and early-onset bipolar disorder. In order to establish causality, this study used an animal model to investigate the effects of advanced paternal age on behavioural deficits in the offspring.

Methods

C57BL/6J offspring (n = 12 per group) were bred from fathers of two different ages, 2 months (young) and 10 months (old), and mothers aged 2 months (n = 6 breeding pairs per group). Social and exploratory behaviors were examined in the offspring.

Principal Findings

The offspring of older fathers were found to engage in significantly less social (p = 0.02) and exploratory (p = 0.02) behaviors than the offspring of younger fathers. There were no significant differences in measures of motor activity.

Conclusions

Given the well-controlled nature of this study, this provides the strongest evidence for deleterious effects of advancing paternal age on social and exploratory behavior. De-novo chromosomal changes and/or inherited epigenetic changes are the most plausible explanatory factors.     

Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring

Aim/Hypothesis

Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers.

Results

Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass.Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected.

Conclusions

Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes in-utero, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.     

Prolactin, fatherhood, and reproductive behavior in human males

Although humans are considered unusual among mammals for the intensity of care that fathers often provide offspring, little is known about the hormonal architecture regulating human paternal investment. Prolactin has important reproductive functions in both female and male mammals and other taxa, making it a candidate regulator of human paternal behavior. Notably, prolactin is higher during periods of offspring care in some species, but it is unknown if this pattern occurs in human fathers. We draw on a sample of men (n = 289; age 21-23 at baseline) from Metropolitan Cebu City, Philippines to evaluate relationships between prolactin, assayed from dried blood spots, and components of reproductive behavior and relationship status. In this sample, fathers had higher prolactin than nonfathers (P = 0.006), and fathers of infants had borderline higher prolactin than fathers of older children (P = 0.054). Among single nonfathers at baseline (2005), baseline prolactin did not predict who transitioned to fatherhood by follow-up 4.5 years later. Among nonfathers, men with greater prolactin reported more lifetime sexual partners (P = 0.050) as well as more sexual activity in the month before sampling (P = 0.060). Our results suggest that fathers in Cebu have higher prolactin than nonfathers, with hormone levels highest among fathers of young infants. Although these findings are generally consistent with evidence from other species for pronurturing effects of prolactin, evidence for positive relationships between the hormone and measures of sexual behavior at Cebu point to likely complexities in the hormone's involvement in male reproductive strategy.     

Paternal behavior influences development of aggression and vasopressin expression in male California mouse offspring

Parental care has been demonstrated to have important effects on offspring behavioral development. California mice (Peromyscus californicus) are biparental, and correlational evidence suggests that pup retrieving by fathers has important effects on the development of aggressive behavior and extra-hypothalamic vasopressin systems. We tested whether retrievals affected these systems by manipulating paternal retrieval behavior between day 15 and 21 postpartum. Licking and grooming behavior affect behavioral development in rats, so we also experimentally reduced huddling and grooming behavior by castrating a subset of fathers. Experimentally increasing the frequency of paternal pup retrieving behavior decreased attack latency in resident-intruder in both male and female adult offspring, whereas experimental reduction of huddling and grooming had no effect. In a separate group of male offspring, we examined vasopressin immunoreactivity (AVP-ir) in two regions of the posterior bed nucleus of the stria terminalis (BNST): the dorsal fiber tracts (dBNST) and the ventral cell body-containing region (vBNST). Experimentally increasing retrievals led to an apparent shift in AVP-ir distribution. Specifically, offspring from the high retrieval group had more AVP-ir than offspring from the sham retrieval group in the dBNST, whereas the opposite was observed in the vBNST. Experimental reduction of paternal grooming was associated with increased AVP-ir in the paraventricular nucleus and also increased corticosterone and progesterone, similar to observed effects of maternal grooming on HPA function. This study provides further evidence that paternal behavior influences the development of aggression and associated neural substrates.     

Early life of fathers affects offspring fitness in a wild rodent

Intergenerational fitness effects on offspring due to the early life of the parent are well studied from the standpoint of the maternal environment, but intergenerational effects owing to the paternal early life environment are often overlooked. Nonetheless, recent laboratory studies in mammals and ecologically relevant studies in invertebrates predict that paternal effects can have a major impact on the offspring's phenotype. These nongenetic, environment‐dependent paternal effects provide a mechanism for fathers to transmit environmental information to their offspring and could allow rapid adaptation. We used the bank vole Myodes glareolus, a wild rodent species with no paternal care, to test the hypothesis that a high population density environment in the early life of fathers can affect traits associated with offspring fitness. We show that the protein content in the diet and/or social environment experienced during the father's early life (prenatal and weaning) influence the phenotype and survival of his offspring and may indicate adaptation to density‐dependent costs. Furthermore, we show that experiencing multiple environmental factors during the paternal early life can lead to a different outcome on the offspring phenotype than stimulated by experience of a single environmental factor, highlighting the need to study developmental experiences in tandem rather than independent of each other.     

父本剥夺对子代棕色田鼠同性间行为及相关脑区神经元活性的影响

为探究父本剥夺对子代棕色田鼠(Microtus mandarinus)同性间行为及相关脑区神经元活性的影响,本实验观察了父本缺失子代棕色田鼠成年后社会互作实验和相关脑区Fos蛋白的表达情况。社会互作实验结果显示,与雄性对照组相比,雄性父本剥夺组田鼠对另一雄性个体的探究和聚团行为显著减少(P0.01);与雌性对照组相比,雌性父本剥夺组田鼠对另一雌性个体的探究行为有减少的趋势,对视和自饰行为显著减少(P0.05);但父本剥夺组雌雄棕色田鼠静止时间均显著增加(P0.05)。免疫组织化学结果显示,通过短暂社会互作后,与雄性对照组相比,父本剥夺组雄性在终纹床核(bed nucleus of the stria terminalis,BST)、杏仁中央核(central nucleus of the amygdale,Ce)和室旁核(paraventricular nucleus of the hypothalamus,PVN)Fos阳性神经元数量显著增加(P0.01);与雌性对照组相比,父本剥夺组雌性在终纹床核(BST)和室旁核(PVN)阳性神经元数量也极显著增加(P0.01)。综上,父本剥夺可能导致幼仔成年后社会性和活动性下降,并可能增加成年后应激反应相关脑区的神经元活性。     

The coevolution of sexual imprinting by males and females

Sexual imprinting is the learning of a mate preference by direct observation of the phenotype of another member of the population. Sexual imprinting can be paternal, maternal, or oblique if individuals learn to prefer the phenotypes of their fathers, mothers, or other members of the population, respectively. Which phenotypes are learned can affect trait evolution and speciation rates. “Good genes” models of polygynous systems predict that females should evolve to imprint on their fathers, because paternal imprinting helps females to choose mates that will produce offspring that are both viable and sexy. Sexual imprinting by males has been observed in nature, but a theory for the evolution of sexual imprinting by males does not exist. We developed a good genes model to study the conditions under which sexual imprinting by males or by both sexes can evolve and to ask which sexual imprinting strategies maximize the fitness of the choosy sex. We found that when only males imprint, maternal imprinting is the most advantageous strategy. When both sexes imprint, it is most advantageous for both sexes to use paternal imprinting. Previous theory suggests that, in a given population, either males or females but not both will evolve choosiness in mating. We show how environmental change can lead to the evolution of sexual imprinting behavior by both sexes in the same population.     

Female Arctic charr do not show apparent benefits from exposing their eggs to sperm from dominant males

To evaluate whether paternal effects occur on offspring traits, eggs from Arctic charr Salvelinus alpinus were fertilized with similar amount of sperm from size-matched dominant and subordinate males, in a nested design. Eggs fertilized by subordinate fathers resulted in more offspring produced than eggs fertilized by the same amount of sperm from dominant fathers. Yet, paternal status showed no significant effect on measurements of larvae total length, yolk area and yolk red intensity.     

Implications of Advancing Paternal Age: Does It Affect Offspring School Performance?

Average paternal age is increasing in many high income countries, but the implications of this demographic shift for child health and welfare are poorly understood. There is equivocal evidence that children of older fathers are at increased risk of neurodevelopmental disorders and reduced IQ. We therefore report here on the relationship between paternal age and a composite indicator of scholastic achievement during adolescence, i.e. compulsory school leaving grades, among recent birth cohorts in Stockholm County where delayed paternity is notably common. We performed a record-linkage study comprising all individuals in Stockholm County who finished 9 years of compulsory school from 2000 through 2007 (n = 155,875). Data on school leaving grades and parental characteristics were retrieved from administrative and health service registers and analyzed using multiple linear regression. Advancing paternal age at birth was not associated with a decrease in school leaving grades in adolescent offspring. After adjustment for year of graduation, maternal age and parental education, country of birth and parental mental health service use, offspring of fathers aged 50 years or older had on average 0.3 (95% CI −3.8, 4.4) points higher grades than those of fathers aged 30–34 years. In conclusion, advancing paternal age is not associated with poorer school performance in adolescence. Adverse effects of delayed paternity on offspring cognitive function, if any, may be counterbalanced by other potential advantages for children born to older fathers.     

The thermal environment of sperm affects offspring success: a test of the anticipatory paternal effects hypothesis in the blue mussel

There has been an explosion of recent evidence that environments experienced by fathers or their ejaculates can influence offspring phenotypes (paternal effects). However, little is known about whether such effects are adaptive, which would have far-reaching implications for the many species facing rapidly changing environments. For example, some arguments suggest paternal effects might be a source of cross-generational plasticity, preparing offspring to face similar conditions to their father (anticipatory hypothesis). Alternatively, ejaculate-mediated effects on offspring may be non-adaptive by-products of stress. Here, we conduct an experiment to distinguish between these predictions, exposing ejaculates of the externally fertilizing mussel Mytilus galloprovincialis to ambient (19°C) and high (24°C) temperatures, then rearing offspring groups in temperatures that match and mismatch those of sperm. We find that, overall, high temperature-treated sperm induced higher rates of normal offspring development and higher success in transitioning to second-stage larvae, which may represent adaptive epigenetic changes or selection on sperm haplotypes. However, the progeny of high temperature-treated sperm did not perform better than those of ambient temperature-treated sperm when rearing temperatures were high. Overall, these findings offer little support for the anticipatory hypothesis and suggest instead that beneficial paternal effects may be eroded when offspring develop under stressful conditions.     

Chronic variable stress in fathers alters paternal and social behavior but not pup development in the biparental California mouse (Peromyscus californicus)

Stress and chronically elevated glucocorticoid levels have been shown to disrupt parental behavior in mothers; however, almost no studies have investigated corresponding effects in fathers. The present experiment tested the hypothesis that chronic variable stress inhibits paternal behavior and consequently alters pup development in the monogamous, biparental California mouse (Peromyscus californicus). First-time fathers were assigned to one of three experimental groups: chronic variable stress (CVS, n = 8), separation control (SC, n = 7), or unmanipulated control (UC, n = 8). The CVS paradigm (3 stressors per day for 7 days) successfully stressed mice, as evidenced by increased baseline plasma corticosterone concentrations, increased adrenal mass, decreased thymus mass, and a decrease in body mass over time. CVS altered paternal and social behavior of fathers, but major differences were observed only on day 6 of the 7-day paradigm. At that time point, CVS fathers spent less time with their pairmate and pups, and more time autogrooming, as compared to UC fathers; SC fathers spent more time behaving paternally and grooming the female mate than CVS and UC fathers. Thus, CVS blocked the separation-induced increase in social behaviors observed in the SC fathers. Nonetheless, chronic stress in fathers did not appear to alter survival or development of their offspring: pups from the three experimental conditions did not differ in body mass gain over time, in the day of eye opening, or in basal or post-stress corticosterone levels. These results demonstrate that chronic stress can transiently disrupt paternal and social behavior in P. californicus fathers, but does not alter pup development or survival under controlled, non-challenging laboratory conditions.     

Epigenetics as a Driver of Developmental Origins of Health and Disease: Did We Forget the Fathers?

What are the effects of our environment on human development and the next generation? Numerous studies have provided ample evidence that a healthy environment and lifestyle of the mother is important for her offspring. Biological mechanisms underlying these environmental influences have been proposed to involve alterations in the epigenome. Is there enough evidence to suggest a similar contribution from the part of the father? Animal models provide proof of a transgenerational epigenetic effect through the paternal germ line, but can this be translated to humans? To date, literature on fathers is scarce. Human studies do not always incorporate appropriate tools to evaluate paternal influences or epigenetic effects. In reviewing the literature, I stress the need to explore and recognize paternal contributions to offspring's health within the Developmental Origins of Health and Disease hypothesis, and coin this new concept the Paternal Origins of Health and Disease paradigm (POHaD). A better understanding of preconceptional origins of disease through the totality of paternal exposures, or the paternal exposome, will provide evidence‐based public health recommendations for future fathers.

     

COMPLEX INTERACTIONS BETWEEN PATERNAL AND MATERNAL EFFECTS: PARENTAL EXPERIENCE AND AGE AT REPRODUCTION AFFECT FECUNDITY AND OFFSPRING PERFORMANCE IN A BUTTERFLY

Parental effects can greatly affect offspring performance and are thus expected to impact population dynamics and evolutionary trajectories. Most studies have focused on maternal effects, whereas fathers are also likely to influence offspring phenotype, for instance when males transfer nutrients to females during mating. Moreover, although the separate effects of maternal age and the environment have been documented as a source of parental effects in many species, their combined effects have not been investigated. In the present study, we analyzed the combined effects of maternal and paternal age at reproduction and a mobility treatment in stressful conditions on offspring performance in the butterfly Pieris brassicae. Both paternal and maternal effects affected progeny traits but always via interactions between age and mobility treatment. Moreover, parental effects shifted from male effects expressed at the larval stage to maternal effects at the adult stage. Indeed, egg survival until adult emergence significantly decreased with father age at mating only for fathers having experienced the mobility treatment, whereas offspring adult life span decreased with increasing mother age at laying only for females that did not experience the mobility treatment. Overall, our results demonstrate that both parents’ phenotypes influence offspring performance through nongenetic effects, their relative contribution varying over the course of progeny's life.     

PATERNAL CARE: DIRECT AND INDIRECT GENETIC EFFECTS OF FATHERS ON OFFSPRING PERFORMANCE

Knowledge of how genetic effects arising from parental care influence the evolution of offspring traits comes almost exclusively from studies of maternal care. However, males provide care in some taxa, and often this care differs from females in quality or quantity. If variation in paternal care is genetically based then, like maternal care and maternal effects, paternal effects may have important consequences for the evolution of offspring traits via indirect genetic effects (IGEs). IGEs and direct–indirect genetic covariances associated with parental care can contribute substantially to total heritability and influence predictions about how traits respond to selection. It is unknown, however, if the magnitude and sign of parental effects arising from fathers are the same as those arising from mothers. We used a reciprocal cross‐fostering experiment to quantify environmental and genetic effects of paternal care on offspring performance in the burying beetle, Nicrophorus vespilloides. We found that IGEs were substantial and direct–indirect genetic covariances were negative. Combined, these patterns led to low total heritabilities for offspring performance traits. Thus, under paternal care, offspring performance traits are unlikely to evolve in response to selection, and variation in these traits will be maintained in the population despite potentially strong selection on these traits. These patterns are similar to those generated by maternal care, indicating that the genetic effects of care on offspring performance are independent of the caregiver's sex.     

Effects of advanced paternal age on trajectories of social behavior in offspring

Our study is the first investigation of the effects of advanced paternal age (APA) on the developmental trajectory of social behavior in rodent offspring. Given the strong epidemiological association between APA and sexually dimorphic neurodevelopmental disorders that are characterized by abnormalities in social behavior (autism, schizophrenia), we assessed sociability in male and female inbred mice (C57BL/6J) across postnatal development (N = 104) in relation to paternal age. We found differences in early social behavior in both male and female offspring of older breeders, with differences in this social domain persisting into adulthood in males only. We showed that these social deficits were not present in the fathers of these offspring, confirming a de novo origin of an altered social trajectory in the offspring generation. Our results, highly novel in rodent research, support the epidemiological observations in humans and provide evidence for a causal link between APA, age‐related changes in the paternal sperm DNA and neurodevelopmental disorders in their offspring.     

Paternal Age in Relation to Offspring Intelligence in the West of Scotland Twenty-07 Prospective Cohort Study

Background

The adverse effects of advancing maternal age on offspring''s health and development are well understood. Much less is known about the impact of paternal age.

Methods

We explored paternal age-offspring cognition associations in 772 participants from the West of Scotland Twenty-07 study. Offspring cognitive ability was assessed using Part 1 of the Alice Heim 4 (AH4) test of General Intelligence and by reaction time (RT).

Results

There was no evidence of a parental age association with offspring RT. However, we observed an inverse U-shaped association between paternal age and offspring AH4 score with the lowest scores observed for the youngest and oldest fathers. Adjustment for parental education and socioeconomic status somewhat attenuated this association. Adjustment for number of, particularly older, siblings further reduced the scores of children of younger fathers and appeared to account for the lower offspring scores in the oldest paternal age group.

Conclusion

We observed a paternal age association with AH4 but not RT, a measure of cognition largely independent of social and educational experiences. Factors such as parental education, socioeconomic status and number of, particularly older, siblings may play an important role in accounting for paternal age-AH4 associations. Future studies should include parental intelligence.     

Sex allocation according to multiple sexually dimorphic traits of both parents in the barn swallow (Hirundo rustica)

Parents should differentially invest in sons or daughters depending on the sex‐specific fitness returns from male and female offspring. In species with sexually selected heritable male characters, highly ornamented fathers should overproduce sons, which will be more sexually attractive than sons of less ornamented fathers. Because of genetic correlations between the sexes, females that express traits which are under selection in males should also overproduce sons. However, sex allocation strategies may consist in reaction norms leading to spatiotemporal variation in the association between offspring sex ratio (SR) and parental phenotype. We analysed offspring SR in barn swallows (Hirundo rustica) over 8 years in relation to two sexually dimorphic traits: tail length and melanin‐based ventral plumage coloration. The proportion of sons increased with maternal plumage darkness and paternal tail length, consistently with sexual dimorphism in these traits. The size of the effect of these parental traits on SR was large compared to other studies of offspring SR in birds. Barn swallows thus manipulate offspring SR to overproduce ‘sexy sons’ and potentially to mitigate the costs of intralocus sexually antagonistic selection. Interannual variation in the relationships between offspring SR and parental traits was observed which may suggest phenotypic plasticity in sex allocation and provides a proximate explanation for inconsistent results of studies of sex allocation in relation to sexual ornamentation in birds.