SMAD4 mutations causing Myhre syndrome are under positive selection in the male germline.

While it is widely thought that de novo mutations (DNMs) occur randomly, we previously showed that some DNMs are enriched because they are positively selected in the testes of aging men. These "selfish" mutations cause disorders with a shared presentation of features, including exclusive paternal origin, significant increase of the father's age, and high apparent germline mutation rate. To date, all known selfish mutations cluster within the components of the RTK-RAS-MAPK signaling pathway, a critical modulator of testicular homeostasis. Here, we demonstrate the selfish nature of the SMAD4 DNMs causing Myhre syndrome (MYHRS). By analyzing 16 informative trios, we show that MYHRS-causing DNMs originated on the paternally derived allele in all cases. We document a statistically significant epidemiological paternal age effect of 6.3 years excess for fathers of MYHRS probands. We developed an ultra-sensitive assay to quantify spontaneous MYHRS-causing SMAD4 variants in sperm and show that pathogenic variants at codon 500 are found at elevated level in sperm of most men and exhibit a strong positive correlation with donor's age, indicative of a high apparent germline mutation rate. Finally, we performed in vitro assays to validate the peculiar functional behavior of the clonally selected DNMs and explored the basis of the pathophysiology of the different SMAD4 sperm-enriched variants. Taken together, these data provide compelling evidence that SMAD4, a gene operating outside the canonical RAS-MAPK signaling pathway, is associated with selfish spermatogonial selection and raises the possibility that other genes/pathways are under positive selection in the aging human testis.

Paternal aging impacts expression and epigenetic markers as early as the first embryonic tissue lineage differentiation.

BACKGROUND: Advanced paternal age (APA) is associated with adverse outcomes to offspring health, including increased risk for neurodevelopmental disorders. The aim of this study was to investigate the methylome and transcriptome of the first two early embryonic tissue lineages, the inner cell mass (ICM) and the trophectoderm (TE), from human blastocysts in association with paternal age and disease risk. High quality human blastocysts were donated with patient consent from donor oocyte IVF cycles from either APA (≥ 50 years) or young fathers. Blastocysts were mechanically separated into ICM and TE lineage samples for both methylome and transcriptome analyses. RESULTS: Significant differential methylation and transcription was observed concurrently in ICM and TE lineages of APA-derived blastocysts compared to those from young fathers. The methylome revealed significant enrichment for neuronal signaling pathways, as well as an association with neurodevelopmental disorders and imprinted genes, largely overlapping within both the ICM and TE lineages. Significant enrichment of neurodevelopmental signaling pathways was also observed for differentially expressed genes, but only in the ICM. In stark contrast, no significant signaling pathways or gene ontology terms were identified in the trophectoderm. Despite normal semen parameters in aged fathers, these significant molecular alterations can adversely contribute to downstream impacts on offspring health, in particular neurodevelopmental disorders like autism spectrum disorder and schizophrenia. CONCLUSIONS: An increased risk for neurodevelopmental disorders is well described in children conceived by aged fathers. Using blastocysts derived from donor oocyte IVF cycles to strategically control for maternal age, our data reveals evidence of methylation dysregulation in both tissue lineages, as well as transcription dysregulation in neurodevelopmental signaling pathways associated with APA fathers. This data also reveals that embryos derived from APA fathers do not appear to be compromised for initial implantation potential with no significant pathway signaling disruption in trophectoderm transcription. Collectively, our work provides insights into the complex molecular mechanisms that occur upon paternal aging during the first lineage differentiation in the preimplantation embryo. Early expression and epigenetic markers of APA-derived preimplantation embryos highlight the susceptibility of the future fetus to adverse health outcomes.

Paternal obesity decreases infant MSC mitochondrial functional capacity.

Besides the well-recognized influence of maternal health on fetal in utero development, recent epidemiological studies appoint paternal pre-conception metabolic health as a significant factor in shaping fetal metabolic programming and subsequently offspring metabolic health; however, mechanisms behind these adaptations remain confined to animal models. To elucidate the effects of paternal obesity (P-OB) on infant metabolism in humans, we examined mesenchymal stem cells (MSCs) which give rise to infant tissue, remain involved in mature tissue maintenance, and resemble the phenotype of the offspring donor. Here, we assessed mitochondrial functional capacity, content, and insulin action in MSC from infants of fathers with overweight (BMI 25-30kg/m2) (P-OW) or obesity (BMI≥30kg/m2) (P-OB), while controlling for maternal intrauterine environment. Compared to P-OW, infant MSCs in the P-OB group had lower intact cell respiration, OXPHOS, and electron transport system capacity, independent of any changes in mitochondrial content. Furthermore, glucose handling, insulin action, and lipid content and oxidation were similar between groups. Importantly, infants in the P-OB group had a greater weight-to-length ratio, which could be in part due to changes in MSC metabolic functioning which precedes and therefore influences infant growth trajectories. These data suggest that P-OB negatively influences infant MSC mitochondria.

Divergence in Reproductive Behaviors Is Associated with the Evolutionary Loss of Parental Care.

AbstractThe mechanisms underlying the divergence of reproductive strategies between closely related species are still poorly understood. Additionally, it is unclear which selective factors drive the evolution of reproductive behavioral variation and how these traits coevolve, particularly during early divergence. To address these questions, we quantified behavioral differences in a recently diverged pair of Nova Scotian three-spined stickleback (Gasterosteus aculeatus) populations, which vary in parental care, with one population displaying paternal care and the other lacking this. We compared both populations, and a full reciprocal F1 hybrid cross, across four major reproductive stages: territoriality, nesting, courtship, and parenting. We identified significant divergence in a suite of heritable behaviors. Importantly, F1 hybrids exhibited a mix of behavioral patterns, some of which suggest sex linkage. This system offers fresh insights into the coevolutionary dynamics of reproductive behaviors during early divergence and offers support for the hypothesis that coevolutionary feedback between sexual selection and parental care can drive rapid evolution of reproductive strategies.

Predator-induced transgenerational plasticity of parental care behaviour in male three-spined stickleback fish across two generations.

Parental care is a critical determinant of offspring fitness, and parents adjust their care in response to ecological challenges, including predation risk. The experiences of both mothers and fathers can influence phenotypes of future generations (transgenerational plasticity). If it is adaptive for parents to alter parental care in response to predation risk, then we expect F1 and F2 offspring who receive transgenerational cues of predation risk to shift their parental care behaviour if these ancestral cues reliably predict a similarly risky environment as their F0 parents. Here, we used three-spined sticklebacks (Gasterosteus aculeatus) to understand how paternal exposure to predation risk prior to mating alters reproductive traits and parental care behaviour in unexposed F1 sons and F2 grandsons. Sons of predator-exposed fathers took more attempts to mate than sons of control fathers. F1 sons and F2 grandsons with two (maternal and paternal) predator-exposed grandfathers shifted their paternal care (fanning) behaviour in strikingly similar ways: they fanned less initially, but fanned more near egg hatching. This shift in fanning behaviour matches shifts observed in response to direct exposure to predation risk, suggesting a highly conserved response to pre-fertilization predator exposure that persists from the F0 to the F1 and F2 generations.

Pesticide exposure triggers sex-specific inter- and transgenerational effects conditioned by past sexual selection.

Environmental variation often induces plastic responses in organisms that can trigger changes in subsequent generations through non-genetic inheritance mechanisms. Such transgenerational plasticity thus consists of environmentally induced non-random phenotypic modifications that are transmitted through generations. Transgenerational effects may vary according to the sex of the organism experiencing the environmental perturbation, the sex of their descendants or both, but whether they are affected by past sexual selection is unknown. Here, we use experimental evolution on an insect model system to conduct a first test of the involvement of sexual selection history in shaping transgenerational plasticity in the face of rapid environmental change (exposure to pesticide). We manipulated evolutionary history in terms of the intensity of sexual selection for over 80 generations before exposing individuals to the toxicant. We found that sexual selection history constrained adaptation under rapid environmental change. We also detected inter- and transgenerational effects of pesticide exposure in the form of increased fitness and longevity. These cross-generational influences of toxicants were sex dependent (they affected only male descendants), and intergenerational, but not transgenerational, plasticity was modulated by sexual selection history. Our results highlight the complexity of intra-, inter- and transgenerational influences of past selection and environmental stress on phenotypic expression.

Contribution of the seminal microbiome to paternal programming.

The field of Developmental Origins of Health and Disease has primarily focused on maternal programming of offspring health. However, emerging evidence suggests that paternal factors, including the seminal microbiome, could potentially play important roles in shaping the developmental trajectory and long-term offspring health outcomes. Historically, the microbes present in the semen were regarded as inherently pathogenic agents. However, this dogma has recently been challenged by the discovery of a diverse commensal microbial community within the semen of healthy males. In addition, recent studies suggest that the transmission of semen-associated microbes into the female reproductive tract during mating has potentials to not only influence female fertility and embryo development but could also contribute to paternal programming in the offspring. In this review, we summarize the current knowledge on the seminal microbiota in both humans and animals followed by discussing their potential involvement in paternal programming of offspring health. We also propose and discuss potential mechanisms through which paternal influences are transmitted to offspring via the seminal microbiome. Overall, this review provides insights into the seminal microbiome-based paternal programing, which will expand our understanding of the potential paternal programming mechanisms which are currently focused primarily on the epigenetic modifications, oxidative stresses, and cytokines.

Paternal starvation affects metabolic gene expression during zebrafish offspring development and lifelong fitness.

Dietary restriction in the form of fasting is a putative key to a healthier and longer life, but these benefits may come at a trade-off with reproductive fitness and may affect the following generation(s). The potential inter- and transgenerational effects of long-term fasting and starvation are particularly poorly understood in vertebrates when they originate from the paternal line. We utilised the externally fertilising zebrafish amenable to a split-egg clutch design to explore the male-specific effects of fasting/starvation on fertility and fitness of offspring independently of maternal contribution. Eighteen days of fasting resulted in reduced fertility in exposed males. While average offspring survival was not affected, we detected increased larval growth rate in F1 offspring from starved males and more malformed embryos at 24 h post-fertilisation in F2 offspring produced by F1 offspring from starved males. Comparing the transcriptomes of F1 embryos sired by starved and fed fathers revealed robust and reproducible increased expression of muscle composition genes but lower expression of lipid metabolism and lysosome genes in embryos from starved fathers. A large proportion of these genes showed enrichment in the yolk syncytial layer suggesting gene regulatory responses associated with metabolism of nutrients through paternal effects on extra-embryonic tissues which are loaded with maternal factors. We compared the embryo transcriptomes to published adult transcriptome datasets and found comparable repressive effects of starvation on metabolism-associated genes. These similarities suggest a physiologically relevant, directed and potentially adaptive response transmitted by the father, independently from the offspring's nutritional state, which was defined by the mother.

The current 'dramatically' high paternal ages at childbirth are not unprecedented.

There is strong individual-level evidence that late fatherhood is related to a wide range of health disorders and conditions in offspring. Over the last decades, mean paternal ages at childbirth have risen drastically. This has alarmed researchers from a wide range of fields. However, existing studies have an important shortcoming in that they lack a long-term perspective. This article is a step change in providing such a long-term perspective. We unveil that in many countries the current mean paternal ages at childbirth and proportions of fathers of advanced age at childbirth are not unprecedented. Taking the detected U-shaped trend pattern into account, we discuss individual- and population-level implications of the recent increases in paternal ages at childbirth and highlight important knowledge gaps. At the individual level, some of the biological mechanisms that are responsible for the paternal age-related health risk might, at least to some degree, be counterbalanced by various social factors. Further, how these individual-level effects are linked to population health and human cognitive development might be influenced by various factors, including technical advances and regulations in prenatal diagnostics.

Offspring overcome poor parenting by being better parents.

The evolutionary repercussions of parental effects-the impact of the developmental environment provided by parents on offspring-are often discussed as static effects that can have negative influences on offspring fitness that may even persist across generations. However, individuals are not passive recipients and may mitigate the persistence of parental effects through their behaviour. Here, we tested how the burying beetle, Nicrophorus orbicollis, a species with complex parental care, responded to poor parenting. We cross-fostered young and manipulated the duration of parental care received and measured the impact on traits of both F1 and F2 offspring to experimentally extricate the effect of poor parenting from other parental effects. As expected, reducing parental care negatively affected traits that are ecologically important for burying beetles, including F1 offspring development time and body size. However, F1 parents that received reduced care as larvae spent more time feeding F2 offspring than parents that received full care as larvae. As a result, both the number and mass of F2 offspring were unaffected by the developmental experience of their parents. Our results show that flexible parental care may be able to overcome poor developmental environments and limit negative parental effects to a single generation.

Paternal immune activation by Poly I:C modulates sperm noncoding RNA profiles and causes transgenerational changes in offspring behavior.

Paternal pre-conceptual environmental experiences, such as stress and diet, can affect offspring brain and behavioral phenotypes via epigenetic modifications in sperm. Furthermore, maternal immune activation due to infection during gestation can reprogram offspring behavior and brain functioning in adulthood. However, the effects of paternal pre-conceptual exposure to immune activation on the behavior and physiology of offspring (F1) and grand-offspring (F2) are not currently known. We explored effects of paternal pre-conceptual exposure to viral-like immune activation on F1 and F2 behavioral and physiological phenotypes using a C57BL/6J mouse model. Males were treated with a single injection (intraperitoneal) of the viral mimetic polyinosinic:polycytidylic acid (Poly I:C: 12 mg/kg) then bred with naïve female mice four weeks after the Poly I:C (or 0.9% saline control) injection. The F1 offspring of Poly I:C treated fathers displayed increased depression-like behavior in the Porsolt swim test, an altered stress response in the novelty-suppressed feeding test, and significant transcriptomic changes in their hippocampus. Additionally, the F1 male offspring of Poly I:C treated F0 males showed significantly increased immune responsivity after a Poly I:C immune challenge (12 mg/kg). Furthermore, the F2 male grand-offspring took longer to enter and travelled significantly shorter distances in the light zone of the light/dark box. An analysis of the small noncoding RNA profiles in sperm from Poly I:C treated males and their male offspring revealed significant effects of Poly I:C on the sperm microRNA content at the time of conception and on the sperm PIWI-interacting RNA content of the male offspring. Notably, eight miRNAs with an FDR < 0.05 (miR-141-3p, miR-126b-5p, miR-669o-5p, miR-10b-3p, miR-471-5p, miR-463-5p, miR-148b-3p, and miR-181c-5p) were found to be significantly downregulated in the sperm of Poly I:C treated males. Collectively, we demonstrate that paternal pre-conceptual exposure to a viral immune challenge results in both intergenerational and transgenerational effects on brain and behavior that may be mediated by alterations in the sperm small noncoding RNA content.

Mimicking bacterial infection in male mice changes sperm small RNA profiles and multigenerationally alters offspring behavior and physiology.

Paternal pre-conceptual exposures, including stress, diet, substance abuse, parasite infection, and viral immune activation via Poly I:C, have been reported to influence the brains and behavior of offspring through sperm epigenetic changes. However, the effects of paternal (F0) pre-conceptual exposure to bacterial-induced immune activation on the behavior and physiology of F1 and F2 generations remain unexplored. We examined this using C57BL/6J mice. Eight-week-old males (F0) received a single intraperitoneal injection of the bacterial mimetic lipopolysaccharide (LPS: 5 mg/kg) or 0.9 % saline (vehicle control) before mating with naïve females at four weeks post-injection. Comprehensive behavioral assessments were conducted to investigate anxiety, social behaviors, depressive-like behaviors and cognition in both the F1 and F2 generations within the age range of 8 to 14 weeks. Results demonstrated that only female offspring of LPS-exposed fathers exhibited reduced anxiety levels in the light/dark box, large open field, and novelty-suppressed feeding test. These F1 female offspring also exhibited heightened sociability in the 3-chambered social interaction test and a reduced preference for saccharin in the saccharin preference test. Additionally, the F1 male offspring of LPS-challenged males demonstrated an increased total distance traveled in the light/dark box and a longer distance covered in the light zone. They also exhibited diminished preference for social novelty in the 3-chambered social interaction test and an elevated novel arm preference index in the Y-maze. In the F2 generation, male descendants of LPS-treated fathers showed reduced latency to feed in the novelty-suppressed feeding test. Additionally, the F2 generation of LPS-challenged fathers, but not the F1 generation, displayed enhanced immune response in both sexes after an acute LPS immune challenge (5 mg/kg). Analysis of sperm small noncoding RNA profiles from LPS-treated F0 mice revealed significant changes at 4 weeks after administration of LPS. These changes included three microRNAs, eight PIWI-interacting RNAs, and two transfer RNAs, exhibiting significant upregulation (mmu-miR-146a-5p, mmu-piR-27082 and mmu-piR-29102) or downregulation (mmu-miR-5110, mmu-miR-467e-3p, mmu-piR-22583, mmu-piR-23548, mmu-piR-36341, mmu-piR-50293, mmu-piR-16583, mmu-piR-36507, Mus_musculus_tRNA-Ile-AAT-2-1 and Mus_musculus_tRNA-Tyr-GTA-1-1). Additionally, we detected 52 upregulated small noncoding RNAs (including 9 miRNAs, 41 piRNAs, and 2 tRNAs) and 7 downregulated small noncoding RNAs (3 miRNAs, 3 piRNAs, and 1 tRNA) in the sperm of F1 offspring from LPS-treated males. These findings provide compelling evidence for the involvement of epigenetic mechanisms in the modulation of brain function and immunity, and associated behavioral and immunological traits, across generations, in response to bacterial infection.

Prolactin modulates changes in parental care behaviour in response to perceived paternity in bluegill sunfish (Lepomis macrochirus).

Prolactin is a hormone conserved across all vertebrates and is renowned for its role in reproduction and parental care. Previous studies on prolactin in fish have primarily relied on administration of mammalian prolactin and have suggested that increases in prolactin lead to greater parental care. However, the influence of endogenous prolactin on fish parental care remains unknown. Here, we measure circulating concentrations of endogenous prolactin during parental care in a fish and link these concentrations to parental care behaviour. We provide evidence that male bluegill sunfish with higher circulating concentrations of prolactin provide more parental care to their offspring. Furthermore, we show that nesting males with experimentally reduced perceived paternity have lower circulating prolactin concentrations and perform fewer parental behaviours, facilitating an adaptive investment in offspring in response to paternity cues. Our findings not only confirm the role of endogenous prolactin in modulating parental care behaviour in a fish but also provide a mechanism underlying the adaptive changes in parental care made in response to perceived paternity.

Effects of paternal deprivation on empathetic behavior and the involvement of oxytocin receptors in the anterior cingulate cortex.

Paternal deprivation (PD) impairs social cognition and sociality and increases levels of anxiety-like behavior. However, whether PD affects the levels of empathy in offspring and its underlying mechanisms remain unknown. The present study found that PD increased anxiety-like behavior in mandarin voles (Microtus mandarinus), impaired sociality, reduced the ability of emotional contagion, and the level of consolation behavior. Meanwhile, PD reduced OT neurons in the paraventricular nucleus (PVN) in both male and female mandarin voles. PD decreased the level of OT receptor (OTR) mRNA in the anterior cingulate cortex (ACC) of male and female mandarin voles. Besides, OTR overexpression in the ACC reversed the PD-induced changes in anxiety-like behavior, social preference, emotional contagion, and consolation behavior. Interference of OTR expression in the ACC increased levels of anxiety-like behaviors, while it reduced levels of sociality, emotional contagion, and consolation. These results revealed that the OTR in the ACC is involved in the effects of PD on empathetic behaviors, and provide mechanistic insight into how social experiences affect empathetic behaviors.

Paternal absence and increased caregiving independently and interactively shape the development of male prairie voles at subadult and adult life stages.

The influence of maternal caregiving is a powerful force on offspring development. The absence of a father during early life in biparental species also has profound implications for offspring development, although it is far less studied than maternal influences. Moreover, we have limited understanding of the interactive forces that maternal and paternal caregiving impart on offspring. We investigated if behaviorally upregulating maternal care compensates for paternal absence on prairie vole (Microtus ochrogaster) pup development. We used an established handling manipulation to increase levels of caregiving in father-absent and biparental families, and later measured male offspring behavioral outcomes at sub-adulthood and adulthood. Male offspring raised without fathers were more prosocial (or possibly less socially anxious) than those raised biparentally. Defensive behavior and responses to contextual novelty were also influenced by the absence of fathers, but only in adulthood. Offensive aggression and movement in the open field test changed as a function of life-stage but not parental exposure. Notably, adult pair bonding was not impacted by our manipulations. Boosting parental care produced males that moved more in the open field test. Parental handling also increased oxytocin immunoreactive cells within the supraoptic nucleus of the hypothalamus (SON), and in the paraventricular nucleus (PVN) of biparentally-reared males. We found no differences in vasopressinergic cell groups. We conclude that male prairie voles are contextually sensitive to the absence of fathers and caregiving intensity. Our study highlights the importance of considering the ways early experiences synergistically shape offspring behavioral and neural phenotypes across the lifespan.

Paternal care plasticity: males care more for early- than late-developing embryos in an arboreal breeding treefrog.

BACKGROUND: Parental care benefits offspring but comes with costs. To optimize the trade-off of costs and benefits, parents should adjust care based on intrinsic and/or extrinsic conditions. The harm to offspring hypothesis suggests that parents should invest more in younger offspring than older offspring because younger offspring are more vulnerable. However, this hypothesis has rarely been comprehensively tested, as many studies only reveal an inverse correlation between parental care and offspring age, without directly testing the effects of offspring age on their vulnerability. To test this hypothesis, we studied Kurixalus eiffingeri, an arboreal treefrog with paternal care. We first performed a field survey by monitoring paternal care during embryonic development. Subsequently, we conducted a field experiment to assess the prevalence of egg predators (a semi-slug, Parmarion martensi) and the plasticity of male care. Finally, we conducted a laboratory experiment to assess how embryo age affects predation by P. martensi. RESULTS: Our results showed that (1) male attendance and brooding frequency affected embryo survival, and (2) males attended and brooded eggs more frequently in the early stage than in the late stage. The experimental results showed that (3) males increased attendance frequency when the predators were present, and (4) the embryonic predation by the semi-slug during the early was significantly higher than in the late stage. CONCLUSIONS: Our findings highlight the importance of paternal care to embryo survival, and the care behavior is plastic. Moreover, our results provide evidence consistent with the predictions of the harm to offspring hypothesis, as males tend to care more for younger offspring which are more vulnerable.

Paternal leakage of plastids rescues inter-lineage hybrids in Silene nutans.

BACKGROUND AND AIMS: Organelle genomes are usually maternally inherited in angiosperms. However, biparental inheritance has been observed, especially in hybrids resulting from crosses between divergent genetic lineages. When it concerns the plastid genome, this exceptional mode of inheritance might rescue inter-lineage hybrids suffering from plastid-nuclear incompatibilities. Genetically differentiated lineages of Silene nutans exhibit strong postzygotic isolation owing to plastid-nuclear incompatibilities, highlighted by inter-lineage hybrid chlorosis and mortality. Surviving hybrids can exhibit variegated leaves, which might indicate paternal leakage of the plastid genome. We tested whether the surviving hybrids inherited the paternal plastid genome and survived thanks to paternal leakage. METHODS: We characterized the leaf phenotype (fully green, variegated or white) of 504 surviving inter-lineage hybrids obtained from a reciprocal cross experiment among populations of four genetic lineages (W1, W2, W3 and E1) of S. nutans from Western Europe and genotyped 560 leaf samples (both green and white leaves for variegated hybrids) using six lineage-specific plastid single nucleotide polymorphisms. KEY RESULTS: A high proportion of the surviving hybrids (≤98 %) inherited the paternal plastid genome, indicating paternal leakage. The level of paternal leakage depended on cross type and cross direction. The E1 and W2 lineages as maternal lineages led to the highest hybrid mortality and to the highest paternal leakage from W1 and W3 lineages in the few surviving hybrids. This was consistent with E1 and W2 lineages, which contained the most divergent plastid genomes. When W3 was the mother, more hybrids survived, and no paternal leakage was detected. CONCLUSIONS: By providing a plastid genome potentially more compatible with the hybrid nuclear background, paternal leakage has the potential to rescue inter-lineage hybrids from plastid-nuclear incompatibilities. This phenomenon might slow down the speciation process, provided hybrid survival and reproduction can occur in the wild.

Guess Who's Coming to Clinic? Companions in a Pediatric Urology Clinic.

INTRODUCTION: Understanding who accompanies children to clinic visits is necessary to engage stakeholders and tailor communication and educational materials. We undertook this study to describe the clinical companions for new patients in a general pediatric urology clinic. METHODS: This retrospective cross-sectional study included all new urology patients aged less than 18 y at a single freestanding quaternary care children's hospital in selected months of 2019 and 2022. Data were collected on patient demographics, diagnosis, level of community disadvantage, and companion present. The number and identities of companions of patients living in more and less disadvantaged neighborhoods were compared. RESULTS: Of 1940 patients, 1014 (52%) were accompanied by mothers alone, 266 (14%) by fathers alone, and 580 (30%) by both mother and father. Mothers were at 85% of clinical visits and fathers at 45% of visits. The likelihood of having one versus two parents present was similar in more and less disadvantaged areas (odds ratio [OR] = 1.11, 95% confidence interval: 0.80-1.55, P = 0.53). When one parent was present, the odds of being accompanied by the mother was lower for patients living in Area Deprivation Index 1-2 (less disadvantaged areas; OR = 0.38, 95% confidence interval: 0.23-0.62, P = 0.0001), and for the father to accompany children aged 12 y and more than infants (OR = 2.16, P = 0.0005) if there was only one parent present. CONCLUSIONS: Our findings highlight opportunities to engage nonmaternal caregivers in pediatric urologic care, to further explore parental decisions around appointment attendance, and to optimize how clinical information is delivered to caregivers who are and are not present during appointments.

Lingering legacies: Past growth and parental experience influence somatic growth in a fish population.

Body size and growth rate can influence individual and population success by mediating fitness. Understanding the factors that influence growth can be difficult to disentangle, however, because growth can be shaped by environmental conditions recently experienced, as well as legacy effects from conditions experienced earlier in life and by parents (via parental effects). To improve understanding of growth among annual cohorts (1982-2015) of Lake Erie Walleye (Sander vitreus), a species with life-history and growth characteristics similar to many other long-lived, iteroparous fishes, we determined the role of the following hypothesised factors: (H1) recent environmental conditions; (H2) traits and experiences of the cohort, including growth, in the previous year; (H3) early-life cohort density; (H4) early-life body size; and (H5) parental composition and environment. We evaluated the relative importance of these hypothesised factors using piecewise structural equation modelling in an information-theoretic framework. Our results indicated that cohort-specific growth of Lake Erie Walleye was most strongly influenced by traits (growth) and experiences of the cohort during the previous year (H2) and parental composition and environment (H5). The observed negative relationship with growth during the previous year may indicate that Walleye exhibit compensatory growth. The relationships with parental sizes and environments may mean that parental contributions to offspring affects cohorts into adulthood, with serious implications for the effects of climate change. Warm winters appear to negatively influence offspring growth performance for many years. Legacy effects had a stronger influence on cohort growth than recent environmental conditions, providing new understanding of how somatic growth is regulated in Lake Erie's Walleye population. Specifically, the parental composition and environment appear important via epigenetic and/or egg-provisioning legacies, with carryover effects modifying growth among years. Ultimately, our findings demonstrate that understanding recent growth in animal populations similar to Lake Erie Walleye may require knowledge of past conditions, including those experienced by parents.

The transgenerational consequences of paternal social isolation and predation exposure in threespined sticklebacks.

Parents routinely encounter stress in the ecological environment that can affect offspring development (transgenerational plasticity: TGP); however, parents' interactions with conspecifics may alter how parents respond to ecological stressors. During social buffering, the presence of conspecifics can reduce the response to or increase the speed of recovery from a stressor. This may have cascading effects on offspring if conspecifics can mitigate parental responses to ecological stress in ways that blunt the transmission of stress-induced transgenerational effects. Here, we simultaneously manipulated both paternal social isolation and experience with predation risk prior to fertilisation in threespined stickleback (Gasterosteus aculeatus). We generated offspring via in-vitro fertilisation to allow us to isolate paternal effects mediated via sperm alone (i.e. in the absence of paternal care). If social buffering mitigates TGP induced by paternal exposure to predation risk, then we expect the transgenerational effects of predation exposure to be weaker when a conspecific is present compared to when the father is isolated. Offspring of predator-exposed fathers showed reduced anxiety-like behaviour and tended to be captured faster by the predator. Fathers who were socially isolated also had offspring that were captured faster by a live predator, suggesting that paternal social isolation may have maladaptive effects on how offspring respond to ecological stressors. Despite additive effects of paternal social isolation and paternal predation risk, we found no evidence of an interaction between these paternal treatments, suggesting that the presence of a conspecific did not buffer fathers and/or offspring from the effects of predation risk. Our results suggest that socially induced stress is an important, yet underappreciated, mediator of TGP and can elicit transgenerational effects even in species that do not form permanent social groups. Future studies should therefore consider how the parental social environment can affect both within and trans-generational responses to ecological stressors.