Transgenerational Effects Research Articles

The Impact of Domestic Violence on the experience of being a mother: a systematic review of the subjective accounts of survivors

Abstract Domestic violence (DV) is still a silent public health pandemic globally, more so during the COVID-19 pandemic. Domestic abuse has a well-documented impact on women and its potential transgenerational consequences for their children. However, the influence of DV on a survivor's experience as a parent is rarely studied, especially in developing nations. Through a systematic review, this study aimed to examine and synthesise current global research on DV survivors' experiences regarding their parenting capacities. The objective was to understand how DV survivors perceive how their parenting capacities were impacted by the experience of DV. Five databases were searched between the periods 2010 to 2020. Fourteen studies met the inclusion criteria. Through a thematic analysis of the included articles, three core themes emerged: first, the mothers’ state of psychosocial and physical health, exacerbated or associated with the DV experience, holds association with their perceived capacity within a parental role. Second, the influence of DV on motherhood is not necessarily predictive of negative parenting practices but somewhat contingent on the mothers’ ability to mobilise supportive internal and external resources, which are often restricted and disrupted by the abusive partner. Last, decisions to leave the abusive partner are complex and subjectively reasoned by the mothers, with a common intention to protect the family. These findings suggest that more comprehensive support and preventative interventions are needed in local communities to create supportive environments that are accessible to mothers who parent in the context of DV.

Seasonally variable thermal performance curves prevent adverse effects of heatwaves.

1. Differential vulnerability to heatwaves may affect community dynamics in a changing climate. In temperate regions, this vulnerability to heatwaves depends on the interactions between seasonal temperature fluctuations and the capacity to rapidly shift thermal performance curves. 2. Here we investigate how these dynamics affect the vulnerability of two ecologically important copepod congeners, Acartia tonsa and A. hudsonica, to heatwaves of different durations. Using a combination of field observations and simulated laboratory heatwave experiments, we uncover strong seasonal variation in the performance curves of A. tonsa but not A. hudsonica. This translated to species-specific seasonal patterns of vulnerability to heatwaves, with increased vulnerability in A. hudsonica. 3. By reducing parental stress during simulated heatwaves, seasonal performance curve shifts likely reduced indirect, transgenerational effects of these events on offspring performance in A. tonsa. 4. Our results illustrate how different levels of seasonal variation in thermal performance curves will affect population persistence in a changing climate.

How does parental diet affect offspring locomotor capacity in the bean bug, Riptortus pedestris?

AbstractParental environments have profound consequences for offspring fitness through transgenerational transmission of resources and epigenetic factors. Locomotor activity is a functional trait of considerable ecological importance, as it determines the ability of animals to find food and mates and to disperse to more favourable environments. Although there have been studies demonstrating that animals can plastically increase their locomotor capacity in response to nutritionally stressful environments, it remains largely unexplored whether and how parental diet can adjust offspring locomotor capacity and its related traits. In this study, we tested the hypothesis that the parental intake of a nutritionally suboptimal diet would induce hyperactivity in the offspring and that this transgenerational effect could lead to improved offspring performance in an insect herbivore, the bean bug (Riptortus pedestris Fabricius) (Hemiptera: Alydidae). We compared the locomotor activity, metabolic phenotype and performance traits of two groups of R. pedestris nymphs born to parents raised on soybeans [Glycine max (L.) Merr, Fabaceae; standard diet] or peanuts (Arachis hypogaea L., Fabaceae; high‐fat diet). Despite being smaller at birth, the offspring of peanut‐fed parents moved faster and more frequently than those of soybean‐fed parents during their early development. The newly hatched offspring born to peanut‐fed parents had higher relative energy reserves in somatic tissues than those born to soybean‐fed parents, indicating that differential parental provisioning could underpin this parental effect on offspring locomotor activity. Possibly through increased foraging activity, the hyperactive offspring of peanut‐fed parents grew faster into heavier adults than the offspring of soybean‐fed parents, implying that parentally induced increase in offspring locomotor activity is adaptive. This study provides experimental evidence for diet‐mediated transgenerational plasticity of locomotor activity in invertebrates and sheds novel insights into the role of parental diet history in shaping offspring phenotype.

17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice

Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.

Investigating the Significance of the Transgenerational Impact of High and Repeated Doses of Ivermectin: Effects on Paternal Testis Histopathology, Pups' Development, and Sexual Behavior

Paternal exposure to environmental challenges is critical for the offspring's future health, and the transmission of acquired traits through generations increases the risk of offspring developing diseases. Ivermectin (IVM) is widely used in veterinary and human medicine to treat parasitosis. Our previous studies showed that IVM acute administration induced disorganization of the germinal epithelium and could cause damage to sperm production. Thus, this study investigated the effects of paternal exposure to repeated high ivermectin doses on paternal testis histology. After mating, their pups' development and sexual behavior in adult rats were examined. Method: Two groups of male rats were treated with IVM or its vehicle once a week for three weeks. We observed these males' body weight, organs and testis histology, and testosterone levels. These rats were mated with females without any treatment: the reproductive performance, the offspring development, and the male and female sexual behavior observed in adulthood. Relative to controls, the IVM paternal testis histology showed hypertrophy and hyperplasia of Leydig cells and increased diameter of the seminiferous tubules—no impairment in reproductive performance. In males and females, the physical and reflexes were modified. In adult age, female rats of the IVM group showed reduced sexual behavior and sexual preferences for the same sex, while male sexual behavior was not altered. Thus, it is possible that paternal exposure to IVM interfered with pups' hormonal and growth factors during development and in adult age. Further studies are needed to explore IVM transgenerational effects identifying possible mechanisms underpinning behavioral effects.

Exposure of Enchytraeus crypticus to ciprofloxacin - A multi- and transgenerational study

The increased consumption of antibiotics and their partial metabolism by the human and animal body have led to the frequent identification of such compounds in various environmental matrices. Ciprofloxacin (CIP) is one of the most widely used antibiotics worldwide and it has low mobility and high sorption to soil, leading to the potential to accumulate and persist on organic fertilizers (manure and sewage sludge) and agricultural soils. Therefore, the presence of CIP in the agricultural environment has become an emerging concern as it may negatively affect soil organisms and soil quality, and contribute to the spread of antibiotic-resistant bacteria, thus threatening food security and public health. In this study, we aimed to evaluate the multigenerational and transgenerational effects of CIP on the reproduction of Enchytraeus crypticus to properly assess the long-term impacts of such exposure. Our results for the multigenerational test showed that the reproduction of the organisms was affected from the third to the last (sixth) generation, highlighting the importance of long-term evaluation. There was also evidence of tolerance to reproduction of E. crypticus, as there was no statistical difference between concentrations for all generations, including for among the last three generations themselves. For the transgenerational tests, almost all results showed no statistical difference from the controls, indicating that the effects of CIP may be reversible when the organisms are transferred to clean media. However, since the last generations in the transgenerational tests showed significant differences from the first of the multigenerational tests, the adverse effects may still persist to some extent in the subsequent generations. Thus, when evaluating the effects of CIP on soil media, its persistence and behavior in this matrix must be considered. We strongly recommend that further long-term exposure studies be conducted and considered in regulatory decision-making, especially for persistent compounds.

Transgenerational Effects on Lifespan and Pathology of Paternal Pre-conceptional Exposure to Continuous Low-dose-rate Gamma Rays in C57BL/6J Mice

The present work investigates the multigenerational effects of paternal pre-conceptional exposure to continuous low-dose-rate gamma rays in C56BL/6J mice. Male C57BL/6J (F0 sires) mice were exposed to low dose rates of 20, 1, and 0.05 mGy/day for 400 days, to total accumulated doses of 8,000, 400, and 20 mGy, respectively. Upon completion of the radiation exposure, the F0 male mice were immediately bred to non-irradiated 8-week-old C57BL/6J females (F0 dams) to produce the first-generation (F1) mice. Randomly selected F1 males and females were then bred to produce the second-generation (F2) mice. All the mice, except the F0 dams, were subjected to pathological examination upon natural death. Reproductive parameters, lifespan, causes of death, neoplasm incidences and non-neoplastic disease incidences were used as parameters to evaluate the biological effects of continuous pre-conceptional exposure of the sires (F0) to continuous low-dose-rate radiation. There were no significant differences in the pregnancy and weaning rates among the parent (F0) generation. Average litter size and average number of weaned pups (F1) from dams bred to males (F0) exposed to 20 mGy/day were significantly decreased compared to the non-irradiated controls. Significant lifespan shortening in the sires (F0) was observed only in the 20 mGy/day group due to early death from malignant lymphomas. Life shortening was also observed in the F1 progeny of sires (F0) exposed to 20 and 1 mGy/day, but could not be attributed to a specific cause. No significant differences in the causes of death were found between dose groups in any generation. The number of primary tumors per mouse was significantly increased only in the F0 males exposed to 20 mGy/day. Except for the increased incidence rate for Harderian gland neoplasms in sires (F0) exposed to 20 mGy/day, there was no significant difference in neoplasm incidences and tumor spectra in all 3 generations in each sex regardless of radiation exposure. No multi- or transgenerational effects in the parameters examined were observed in the F1 and F2 progeny of sires exposed to 0.05 mGy/day for 400 days.

Heritable heart failure traits in mice undergoing early life stress

Abstract Introduction Adverse childhood experiences, known as early life stress (ELS), are associated with increased cardiovascular disease risk in later life, yet the underlying mechanisms remain elusive. Recent evidence indicates that parental life experiences can be transmitted to the offspring. Whether ELS exerts transgenerational effects on the heart is unknown. Purpose To investigate the effects of ELS on cardiac structure and function in exposed parents and in their offspring, across 3 generations. Methods We used a mouse model of ELS (MSUS) that mimics the exposure to traumatic experiences during childhood in humans. Mouse pups (F1) were separated from their mother (F0) unpredictably each day for 3 hours from postnatal day 1 (PND1) to PND14. During separation, dams were exposed to an additional unpredictable stressor by being subjected to either, a forced swim (18°C water for 5 minutes) or a 20-minute physical tube restraint, anytime (unpredictably) during the 3 hours. From PND15, mice are left undisturbed with their mother until PND21, are then raised normally until adulthood. Control litters were raised normally. A high-resolution Micro-Ultrasound System (Vevo 3100, Visualsonics) was used for the echocardiographic assessment at 6, 12 and 18 months both in the exposed animals (F0) as well as in their offspring (F1) and grandoffspring (F2). Both male and female mice were studied. Heart weight/tibia length and left ventricle weight/tibia length were used to assess cardiac mass while myocardial fibrosis was assessed by Masson's Trichrome and Picriosirius Red stainings. Lung congestion was assessed as lung wet/dry weight ratio. Single cell RNA sequencing (scRNAseq) was used in LV specimens from MSUS mice to unveil cell-specific transcriptional changes. Finally, MSUS mice underwent environmental enrichment (cages containing running wheels, maze) to investigate any rescuing effect on cardiac function. Results F1 mice displayed increased LV mass, impaired diastolic function, myocardial fibrosis and lung congestion. A time-dependent worsening of cardiac performance was observed from 6 to 18 months, both in males and females. ScRNAseq unveiled dysregulation of transcriptional programs underlying inflammation and lipotoxicity in the cardiomyocyte and endothelial cell clusters. The MSUS offspring did not show changes of cardiac function at 6 months, however diastolic dysfunction and lung congestion were observed at 12 and 18 months. A similar impairment of cardiac function was observed in the MSUS grandoffspring (F3). Of interest, 6-week exposure to an environmental enrichment protocol was able to improve LV mass, diastolic function and lung congestion in 12 months-old MSUS mice. Conclusions ELS induces a transgenerational transmission of cardiac phenotypic alterations which can be rescued by EE. Our results shed light on the potential role of ELS on heart failure development and potential mitigation strategies.

Environmental Pollutant Anthracene Induces ABA-Dependent Transgenerational Effects on Gemmae Dormancy in Marchantia polymorpha.

Anthracene, a polycyclic aromatic hydrocarbon (PAH) from fossil fuel combustion, poses significant environmental threats. This study investigates the role of abscisic acid (ABA) in the anthracene tolerance of the liverwort Marchantia polymorpha using mutants deficient in ABA perception (Mppyl1) or biosynthesis (Mpaba1). In this study, we monitored the role of ABA in the anthracene tolerance response by tracking two ABA-controlled traits: plant growth inhibition and gemmae dormancy. We found that the anthracene-induced inhibition of plant growth is dose-dependent, similar to the growth-inhibiting effect of ABA, but independent of ABA pathways. However, gemmae dormancy was differentially affected by anthracene in ABA-deficient mutants. We found that gemmae from anthracene-exposed WT plants exhibited reduced germination compared to those from mock-treated plants. This suggests that the anthracene exposure of mother plants induces a transgenerational effect, resulting in prolonged dormancy in their asexual propagules. While Mppyl1 gemmae retained a dormancy delay when derived from anthracene-exposed thalli, the ABA biosynthesis mutant Mpaba1 did not display any significant dormancy delay as a consequence of anthracene exposure. These results, together with the strong induction of ABA marker genes upon anthracene treatment, imply that anthracene-induced germination inhibition relies on ABA synthesis in the mother plant, highlighting the critical role of MpABA1 in the tolerance response. These findings reveal a complex interplay between anthracene stress and ABA signaling, where anthracene triggers ABA-mediated responses, influencing reproductive success and highlighting the potential for leveraging genetic and hormonal pathways to enhance plant resilience in contaminated habitats.

DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism

There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.

Toxicity of parental co-exposure of microplastic and bisphenol compounds on adult zebrafish: Multi-omics investigations on offspring

In recent years, the widespread use of bisphenol compounds and microplastics (MP) have attracted attention due to their harmful effects. Here, individual and combined effects of MP and bisphenol compounds, were assessed on adult zebrafish after co-exposure of bisphenol A (BPA) or bisphenol S (BPS) and 25 μm polyethylene MP. Impacts on their offspring (the F1 generation) were also investigated. The reproductive toxicity in adult zebrafish impacted exerted by bisphenol compounds were aggravated by the co-presence of MP. Transcriptomics and metabolomics further showed single or co-exposure of bisphenol compounds and MP could together regulate apoptosis, calcium signaling pathway and glycerophospholipid signaling pathways. Our results also showed the different toxicity mechanisms on transcriptional and metabolic profiles in the combination effects of bisphenol compounds and MP. The co-exposure of BPA and MP predominantly influenced neurotoxicity via the MAPK signaling pathway and voltage-dependent calcium channels, whereas the co-exposure of BPS and MP principally affected visual development through phototransduction and retinol metabolism. The co-exposure of BPA and MP, as well as BPS and MP, specifically regulate lipid metabolism and carbohydrate metabolism in zebrafish offspring, respectively. Overall, this study provided a deep understanding of the toxicity differences between co-exposure and single exposure of bisphenol compound and MP in zebrafish, as well as the transgenerational effects and potential molecular mechanisms of bisphenol compounds and MP in zebrafish offspring.

Preimaginal treatment of Trichogramma evanescens and T. pintoi with two novel insecticides, afidopyropen and broflanilide: the lethal, sublethal and transgenerational effects

Preimaginal treatment of Trichogramma evanescens and T. pintoi with two novel insecticides, afidopyropen and broflanilide: the lethal, sublethal and transgenerational effects

Effect of environmental air pollutants on placental function and pregnancy outcomes: a molecular insight.

Air pollution has become a major health concern, particularly for vulnerable populations such as the elderly, children, and pregnant women. Studies have reported a strong association between prenatal exposure to air pollutants and adverse pregnancy outcomes, including lower birth weight, reduced fetal growth, and an increased frequency of preterm births. This review summarizes the harmful effects of air pollutants, such as particulate matter, on pregnancy and outlines the mechanistic details associated with these adverse outcomes. Particulate pollutant matter may be able to cross the placenta barrier, and alterations in placental functions are central to the detrimental effects of these pollutants. In addition to associations with preeclampsia and gestational hypertension, air pollutants also induce oxidative stress, inflammation, and epigenetic alteration in the placenta. These pollutants can also affect placental homeostasis and endocrine function, contributing to pregnancy complications and possible transgenerational effects. Prenatal air pollution exposure has been linked to reduced cognitive and motor function in infants and newborns, increasing the predisposition to autism spectrum disorders and other neuropsychiatric disorders. This review also summarizes the use of various animal models to study the harmful effects of air pollution on pregnancy and postnatal outcomes. These findings provide valuable insight into the molecular events associated with the process and can aid in risk mitigation and adopting safety measures. Implementing effective environmental protocols and taking appropriate steps may reduce the global disease burden, particularly for developing nations with poor regulatory compliance and large populations of pregnant women.

Carryover effects of tire wear particle leachate threaten the reproduction of a model zooplankton across multiple generations.

The toxic additives that leach from tire wear particles (TWPs) cause mass die-offs in fish and impact zooplankton as secondary consumers in the aquatic food web. In addition to the direct impacts of TWP leachate on a single generation, there may be potential delayed carryover effects across multiple generations from parental exposure, which may amplify the adverse effects of the leachate on individual reproduction and, consequently, on the entire population. In this study, the single, multiple, and transgenerational effects of TWP leachate at various concentrations on the reproduction and lifespan of the rotifer Brachionus calyciflorus were investigated. The results indicated that the lifespan and reproductive output of rotifers exposed to TWP leachate (0-1500 mg/L) decreased as the concentration increased above 250 mg/L. There was a clear multigenerational effect of TWP leachate on rotifer reproduction. The inhibition rates were consistently greater at 500 mg/L than at 250 mg/L leachate. Although the reproduction of rotifers exposed to 250 mg/L TWP leachate increased in the first two generations (P and F1), it was inhibited in subsequent generations. The inhibitory effect of 500 mg/L TWP leachate persisted across all generations, leading to population extinction by the F4 generation. A significant transgenerational effect of TWP leachate was found on reproduction. The adverse impact of exposure to 250 mg/L leachate for fewer than three generations could be reversed when offspring were transferred to clean media. However, this recovery was not observed after continuous exposure for more than four generations. Exposure to high-dose TWP leachate also caused irreversible damage to reproduction. Therefore, TWP leachate can result in cascading toxicity on zooplankton populations through carryover and cumulative effects on reproduction.

“In the Footsteps of Our Ancestors” Polish Traditions of Westward Migration Meets Modern Epigenetics of Trauma

For several years, there have been ongoing considerations regarding the interdisciplinary connections between the natural sciences and the humanities. The same holds true for the question as to whether trauma can be inherited biologically as well as culturally. Today, this topic is increasingly steering the scientific debate in the direction of epigenetic research, which currently combines molecular biology and social psychology with their respective hallmarks. Can culture-related traumas be inherited and, if this was possible, can transgenerational consequences of trauma be passed on to subsequent generations? The focus remains on educational and socialization-related conduct as well on biologically inherited processes of how individual deals with their own trauma. Can migration be inherited by subsequent generations via transgenerational transmission of trauma? In order to answer this question, both consequences and causes of the long-running migration from Poland to Western European countries need to be considered. This article thus seeks to establish a connection between now and then, while also focusing on tragic passages in Poland’s history that were characterized by suffering, statelessness, and occupation (until 1989). Consequently, multi-layered and repeated habitus breakages as well as specific Polish “worldviews” may have emerged, which tend to favour migration. The causal links between the transgenerational transmission of such traumas and their causal connections to ongoing migration from Poland to countries such as Germany are addressed by using modern epigenetics.

Cancer mortality risk in the Urals Cohort of Exposed Population Offspring

The objective of the study is to analyze solid cancer mortality and estimate the risk value of solid cancer mortality in the offspring of parents irradiated in the Southern Urals, depending on the dose to the parents' gonads as well as to conduct a preliminary assessment of the mortality risk from cancer of individual locations depending on the gonadal dose. The issue of the transgenerational effects of the human gonad exposure is still very important. There exists conclusive evidence of the presence of such effects in experimental animals. However, there is no proof of the existence of these effects in humans despite a great number of research on this subject. International scientific community and international organizations, UNSCEAR and ICRP being among them, regard this issue as the one that has not been solved yet and requires further studies. Urals Cohort of offspring of the population exposed on the Techa River and on the territory of the East Ural radioactive trace was established in the Urals research Center for Radiation medicine in 2022. The key feature of the cohort is the exclusion of the offspring with postnatal exposure. The size of the cohort as of September 2023 is 31,154 persons. The number of person-years over the whole follow-up period from 1950 through 2020 is 1 226 380. Mean dose to the gonads of mothers of all the cohort members is 41 mGy, to those of the fathers' — 35 mGy, mean combined gonad dose is 76 mGy. Over the whole follow-up period 3,774 deaths from all causes including 284 deaths from solid cancers were registered in the cohort. The mean age of the cohort members at the end of the follow-up period was 42 years. The risk of death was analyzed using Poisson regression by the programs of the EPICURE statistical software package. Three models of dose dependence were tested: linear, quadratic, and linear-quadratic models of paternal gonadal dose, maternal gonadal dose, and total gonadal dose. Mortality risk analysis of all solid cancers in the offspring cohort showed no statistically significant effect with parental gonadal dose (we have obtained positive although statistically insignificant values of solid cancers mortality risk) which is consistent with the results of other studies in human populations. At the same time, the analysis for the first time obtained a statistically significant linear dependence of the solid cancer mortality risk in offspring with father's age over 45 years depending on the dose to the father's gonads. The excess relative risk of death was 8.09/Gy, (0.51-22.93), p < 0.05. Also, for the first time, evidence of dose dependence of the mortality risk of lung cancer in male offspring on maternal gonadal dose, paternal gonadal dose, and combined gonadal dose was obtained. The values of excess relative risk of lung cancer and 95% confidence intervals according to the linear model were 5.39/Gy (0.46; 15.56) from paternal gonad dose, 4.36/Gy (0.15; 13.48) from maternal gonad dose, and - 3.95/Gy (0.55; 12.14) from combined gonad dose. Point risk estimates of lung cancer at this stage are characterized by wide confidence intervals and require additional studies to assess the influence of possible effect modifiers, but with a high degree of probability indicate the presence of dose dependence of this effect. Increasing the follow-up period and attained age, will increase the number of cancers in the future and will reduce dose response uncertainties and provide more accurate estimates of the risk of death in the offspring cohort.

Which is the current knowledge on man-made endocrine- disrupting chemicals in follicular fluid? An overview of effects on ovarian function and reproductive health.

The increase in female reproductive disorders, such as polycystic ovary syndrome, endometriosis, and diminished ovarian reserve that lead to subfertility and infertility, has encouraged researchers to search and discover their underlying causes and risk factors. One of the crucial factors that may influence the increasing number of reproductive issues is environmental pollution, particularly exposure to man-made endocrine-disrupting chemicals (EDCs). EDCs can interfere with the ovarian microenvironment, impacting not only granulosa cell function but also other surrounding ovarian cells and follicular fluid (FF), which all play essential roles for oocyte development, maturation, and overall reproductive function. FF surrounds developing oocytes within an ovarian follicle and represents a dynamic milieu. EDCs are usually found in biological fluids, and FF is therefore of interest in this respect. This narrative review examines the current knowledge on specific classes of EDCs, including industrial chemicals, pesticides, and plasticizers, and their known effects on hormonal signaling pathways, gene expression, mitochondrial function, oxidative stress induction, and inflammation in FF. We describe the impact of EDCs on the development of reproductive disorders, oocyte quality, menstrual cycle regulation, and their effect on assisted reproductive technique outcomes. The potential transgenerational effects of EDCs on offspring through animal and first-human studies has been considered also. While significant progress has been made, the current understanding of EDCs' effects on ovarian function, particularly in humans, remains limited, underscoring the need for further research to clarify actions and effects of EDCs in the ovary.

Bugs on Drugs: Paracetamol Exposure Reveals Genotype-Specific Generational Effects on Life History Traits in Drosophila melanogaster.

Few investigations have been made to determine whether pharmaceutical drugs cause any generational effects. These effects can be divided into intergenerational and transgenerational effects. In insects, the F1 offspring of exposed individuals are considered to show intergenerational effects (as they have been exposed as germ cells or early embryos), while the F2 generation is fully non-exposed and considered to show transgenerational effects. Here, the common over-the-counter (OTC) drug, paracetamol, is investigated for genotype-specific responses and effects across generations on three life-history traits: fecundity, longevity, and spontaneous locomotor activity levels in the model species Drosophila melanogaster. Seven isofemale D. melanogaster lines were exposed to a high and intermediate dose of paracetamol determined by a dose-response curve. NMR investigations verified the long-term presence of paracetamol in the food substrate. Phenotypic effects of paracetamol ingestion were investigated on flies exposed to the drug and in their offspring and grand-offspring. The dose-response curve indicated genotype-specific responses to paracetamol. In the following experiment, all traits investigated displayed significant effects of paracetamol ingestion for at least one of the seven isofemale lines, and we detected strong genotype-specific responses to paracetamol. Fecundity tended to increase in individuals directly exposed to the drug whereas fecundity in the F2 generation was reduced (transgenerational). Longevity generally decreased in directly exposed individuals but tended to increase in F1 offspring (intergenerational). Paracetamol effects on spontaneous locomotor activity were primarily detected as transgenerational effects and were rarely seen in directly exposed individuals. However, across lines, no clear overall trend could be determined for any trait. The generational effects and marked genotype-specific response to paracetamol warrants further investigation of both genotype-specific responses and generational effects in general.

Morphometric analysis of the intergenerational effects of protein restriction on nephron endowment in mice

BackgroundParental nutritional status is crucial in shaping offspring's kidney development. However, the association between a protein-restrictive diet and its intergenerational impact on kidney development remains unclear. MethodsWe conducted multigenerational morphometric measurements to investigate the effects of parental protein deprivation on offspring kidney development across four generations. F0 mice were divided into two groups and fed a normal protein diet (NPD) or a low-protein diet (LPD) for three weeks before mating and continued these diets throughout gestation and lactation. Body weight (BW), kidney weight (KW), KW/BW ratio, nephron counts, and blood pressure were assessed in F1 pups. To examine paternal effects, we bred CD1 females on an NPD with males on an LPD. BW, KW, KW/BW, and nephron counts were measured at P20. To measure the transgenerational effect of parental LPD on kidney development, F1 offspring (from parents on LPD) were fed NPD upon weaning. These F1 offspring were bred at 6 weeks of age to produce F2, F3 and F4 generations. Kidney metrics were evaluated across generations. ResultsThe average body weight of P0 pups from parents on NPD was 1.61g, while pups from parental LPD weighed an average of 0.869g, a decrease of 54 % (p = 6.9e-11, Wilcoxon test). F1 from parental LPD have significantly smaller kidneys than the control, with an average combined kidney weight of 0.0082g versus 0.0129g, a 37 % decrease (p = 3.2e-02, Wilcoxon test). P20 BW and KW remained low in LPD offspring. These effects persisted for 4 generations (F1 to F4) with an average glomerular count reduction of roughly 20 %. F3 and F4 showed wider variability in glomerular counts but were not statistically significant compared to controls. ConclusionsBoth maternal and paternal LPD significantly affected offspring nephron endowment. Our study underscores the complex nature of nutritional transgenerational effects on kidney development, emphasizing the importance of both maternal and paternal dietary impacts on kidney development and the developmental origin of adult disease.

Thermally Primed Zostera muelleri Seeds Exhibit Higher Germination Rates Than Those From Ambient Conditions.

Seagrasses provide critical ecosystem services such as carbon sequestration, sediment stabilisation and nursery habitat for juvenile fish. Zostera muelleri is ubiquitous within Australian and New Zealand estuaries, however, as a species is relatively understudied. We sourced seeds from a thermally affected east Australian estuary and investigated whether germination rates differed between ambient and thermally affected seeds over a variety of temperatures (16°C-28°C) to determine how seagrass systems might react in a warming climate. Germination for the experiment was low and totalled 5% of all seeds; however, similar numbers are typical in seed germination studies. Germination was highest at 16°C and was enhanced through the simulation of a 48-h freshwater pulse. Thermally affected sites germinated faster and had greater mean maximum germination when compared to control sites regardless of experimental temperature. These findings indicate that Z. muelleri in this system may be exhibiting transgenerational plasticity due to the thermal stress the parent experiences. This result provides an alternate viewpoint to the current literature by suggesting that unknown transgenerational effects may provide Z. muelleri with greater germination plasticity against temperatures expected under predicted climate change scenarios than previously expected.