Paternal Exposure Research Articles

Challenges in using data on fathers/partners to study prenatal exposures and offspring health.

Paternal exposures (and other non-maternal factors) around pregnancy could have important effects on offspring health. One challenge is that data on partners are usually from a subgroup of mothers with data, potentially introducing selection bias, limiting generalisability of findings. We aimed to investigate the potential for selection bias in studies using partner data.We characterise availability of data on father/partner and mother health behaviours (smoking, alcohol, caffeine and physical activity) around pregnancy from three UK cohort studies: the Avon Longitudinal Study of Parents and Children (ALSPAC), Born in Bradford and the Millennium Cohort Study. We assess the extent of sample selection by comparing characteristics of families where fathers/partners do and do not participate. Using the association of parental smoking during pregnancy and child birthweight as an example, we perform simulations to investigate the extent to which missing father/partner data may induce bias in analyses conducted only in families with participating fathers/partners.In all cohorts, father/partner data were less detailed and collected at fewer timepoints than mothers. Partners with a lower socio-economic position were less likely to participate. In simulations based on ALSPAC data, there was little evidence of selection bias in associations of maternal smoking with birthweight, and bias for father/partner smoking was relatively small. Missing partner data can induce selection bias. In our example analyses of the effect of parental smoking on offspring birthweight, the bias had a relatively small impact. In practice, the impact of selection bias will depend on both the analysis model and the selection mechanism.

Safety concerns of paternal drug exposure on fertility, pregnancy and offspring: An analysis based on the FDA adverse event reporting system.

Growing evidence indicates that paternal condition significantly influences pregnancy outcomes and offspring health. However, assessing the safety of paternal drug exposure via randomized controlled trials poses ethical challenges, and relevant clinical studies consume a lot of resources to evaluate only a few drugs. Currently, safety data on paternal drug exposure are scarce. To investigate the impact of paternal drug exposure on fertility, pregnancy outcomes, and offspring health. Data from the FDA adverse event reporting system (FAERS) were analyzed (2010-2022). Disproportionality analyses were used to identify signals of each drug-adverse event pair associated with paternal drug exposure in a different hierarchical manner. Out of the 16,180,533 reports, 3210 were related to paternal exposure, encompassing 7808 concomitant adverse events. Drugs used to treat rheumatoid arthritis, cancer, and infections were primary sources of paternal exposure. Analysis identified 115 signals concerning reproductive health. Notably, the signals of diazepam-small for dates baby and finasteride-cryptorchidism were particularly significant (reporting odds ratio, ROR>800, N>10). Moreover, spontaneous abortion signals occur frequently in biologics for the treatment of immune inflammation; the use of immunosuppressive drugs was associated with the highest number of congenital anomalies, with the strongest signals for belatacept-skeletal dysplasia, and tacrolimus-talipes. Only mycophenolic acid, estrogen and imatinib have signals on male fertility. Anti-tumor agents had high numbers of each reproductive toxicity, with the highest values of trisomy 13 signals associated with etoposide and cisplatin. This is the first research to fully assess the safety of paternal exposure to the majority of medications in terms of reproduction. Clinical and scientific researchers should pay close attention to the list of risk medications included in this study, particularly the following association combinations: biologics used to treat inflammatory diseases-abortion, diazepam-small for date baby, finasteride-cryptorchidism, etoposide and cisplatin-13 trisomy.

Paternal preconception donepezil exposure enhances learning in offspring

BackgroundRecent research has indicated that parental use of central nervous system-targeting medications during periconceptional periods may affect offspring across various developmental and behavioral domains. The present study sought to investigate the potential influence of paternal use of donepezil, a specific reversible central acetylcholinesterase inhibitor that activates the cholinergic system to promote cognition, on offspring.ResultsIn this study, male rats were bred after 21 days of oral donepezil administration at a dose of 4 mg/kg to generate F1 offspring. Both male and female F₁ offspring displayed enhanced performance in learning and short-term memory tests, including novel object recognition, Y maze, and operant learning. Transcriptomic analysis revealed notable alterations in genes associated with the extracellular matrix in the hippocampal tissue of the F1 generation. Integration with genes related to intelligence identified potential core genes that may be involved in the observed behavioral enhancements.ConclusionsThese findings indicate that prolonged paternal exposure to donepezil may enhance the learning and memory abilities of offspring, possibly by targeting nonneural, extracellular regions. Further research is required to fully elucidate any potential transgenerational effects.

Paternal exposure to antiseizure medications and offspring outcomes: a systematic review

BackgroundConcerns have recently been raised about risks to the fetus resulting from paternal exposure to antiseizure medications (ASMs). To address these concerns, we conducted a systematic review of the literature...

Sperm miR-142-3p Reprogramming Mediates Paternal Pre-Pregnancy Caffeine Exposure-Induced Non-Alcoholic Steatohepatitis in Male Offspring Rats.

Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre-pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE-induced non-alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15-60mgkg-1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR-142-3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR-142-3p mitigated these manifestations. The origin of reduced miR-142-3p levels is traced to hypermethylation in the miR-142-3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR-142-3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR-142-3p as a potential therapeutic target for NASH induced by paternal environmental adversities.

Treatment of spondyloarthritis with disease-modifying anti-rheumatic drugs during pregnancy and breastfeeding: comparing the recommendations and guidelines of the principal societies of rheumatology.

This paper aims to provide an overview of the use of treatments available for axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) during pregnancy and breastfeeding, according to current national recommendations and international guidelines, as well as data on the impact on pregnancy outcomes of paternal exposure to treatment. We performed a narrative review of national and international recommendations and guidelines on the reproductive health of patients suffering from rheumatic diseases. The last updated recommendations and guidelines were considered source data. We reported updated information regarding the treatment of axSpA and PsA with nonsteroidal anti-inflammatory drugs, intra-articular glucocorticoids, conventional synthetic disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, and targeted synthetic DMARDs during the preconception period, pregnancy, and breastfeeding, as well as data related to paternal exposure. We highlighted any medications that should be discontinued and/or not used in the reproductive age group and also treatments that may be continued, avoiding the withdrawal of drugs that can be used in the different phases, thus preventing the risk of increasing disease activity and flares before, during, and after pregnancy in SpA patients. The best management of pregnancy in patients with SpA is based on knowledge of updated drug recommendations, a careful and wise evaluation of the risks/benefits of starting or continuing treatment from the SpA diagnosis in a woman of childbearing age through pregnancy and lactation, and sharing therapeutic choices with other healthcare providers (in particular, gynecologists/obstetricians) and the patient.

Multifaceted paternal exposures before conception and their epigenetic impact on offspring.

As scientific research progresses, there is an increasing understanding of the importance of paternal epigenetics in influencing the health and developmental path of offspring. Prior to conception, the environmental exposures and lifestyle choices of fathers can significantly influence the epigenetic state of sperm, including DNA methylation and histone changes, among other factors. These alterations in epigenetic patterns have the potential for transgenerational transmission potential and may exert profound effects on the biological characteristics of descendants. Paternal epigenetic changes not only affect the regulation of gene expression patterns in offspring but also increase the risk to certain diseases. It is crucial to comprehend the conditions that fathers are exposed to before conception and the potential outcomes of these conditions. This understanding is essential for assessing personal reproductive decisions and anticipating health risks for future generations. This review article systematically summarizes and analyzes current research findings regarding how paternal pre-pregnancy exposures influence offspring as well as elucidates underlying mechanisms, aiming to provide a comprehensive perspective for an enhanced understanding of the impact that paternal factors have on offspring health.

Paternal and Maternal Exposures to Per- And Polyfluoroalkyl Substances and Child Behavioral Difficulties

Paternal and Maternal Exposures to Per- And Polyfluoroalkyl Substances and Child Behavioral Difficulties

Paternal Exposure: Two patients' perspectives in an evolving landscape of therapeutics. Can we now provide reassurance?

There is now substantial evidence of safety in pregnancy for several newer medications, particularly biologic disease-modifying antirheumatic drugs, although clinician confidence varies. There is much less information available regarding paternal exposure. This article provides insight from two patients who describe the impact of family planning on their therapeutic decision making.

Substance-Induced Psychiatric Disorders, Epigenetic and Microbiome Alterations, and Potential for Therapeutic Interventions.

Substance use disorders (SUDs) are complex biopsychosocial diseases that cause neurocognitive deficits and neurological impairments by altering the gene expression in reward-related brain areas. Repeated drug use gives rise to alterations in DNA methylation, histone modifications, and the expression of microRNAs in several brain areas that may be associated with the development of psychotic symptoms. The first section of this review discusses how substance use contributes to the development of psychotic symptoms via epigenetic alterations. Then, we present more evidence about the link between SUDs and brain epigenetic alterations. The next section presents associations between paternal and maternal exposure to substances and epigenetic alterations in the brains of offspring and the role of maternal diet in preventing substance-induced neurological impairments. Then, we introduce potential therapeutic agents/approaches such as methyl-rich diets to modify epigenetic alterations for alleviating psychotic symptoms or depression in SUDs. Next, we discuss how substance use-gut microbiome interactions contribute to the development of neurological impairments through epigenetic alterations and how gut microbiome-derived metabolites may become new therapeutics for normalizing epigenetic aberrations. Finally, we address possible challenges and future perspectives for alleviating psychotic symptoms and depression in patients with SUDs by modulating diets, the epigenome, and gut microbiome.

Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model.

Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated β-galactosidase activity. Strikingly, in the male offspring, we observe an interaction between maternal and paternal alcohol use, with histological indicators of accelerated age-related liver disease in the dual-parental offspring exceeding those induced by either maternal or paternal alcohol use alone. Our studies indicate that chronic parental alcohol use causes enduring mitochondrial dysfunction in offspring, resulting in a reduced NAD+/NAHD ratio and altered expression of the NAD+-dependent deacetylases SIRT1 and SIRT3. These observations suggest that some aspects of FASDs may be linked to accelerated aging due to programmed changes in the regulation of mitochondrial function and cellular bioenergetics.

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.

Birth defects among offspring of California firefighters, 2007–2019

PurposeLimited research examines birth defects from maternal or paternal firefighting exposure. This study aims to assess if maternal or paternal occupational exposure to firefighting during periconception is associated with offspring birth defects. MethodsData from California birth certificates (2007–2019) were linked to maternal / offspring hospitalization records. Occupation during the periconceptional period was categorized from vital statistics as the following: paternal non-firefighting (n = 4,135,849), paternal firefighting (n = 22,732), maternal non-firefighting (n = 3,332,255) and maternal firefighting (n = 502). Birth defects were identified using ICD codes, grouped by anatomical regions. Adjusted odds ratios were estimated, and sensitivity analyses explored police officer reference groups and detailed birth defect categories. ResultsOffspring of paternal firefighters had lower odds of circulatory defects (aOR = 0.9, 95% CI 0.8, 1.0), oral clefts (aOR = 0.6, 95% CI 0.4, 0.8) and respiratory defects (0.7, 95% CI 0.6, 0.9) compared to paternal non-firefighters. Associations between maternal firefighting and offspring birth defects were imprecise. Substituting police officers as the reference group attenuated findings. ConclusionsOffspring of paternal firefighters may have similar or slightly lower birth defect odds compared to offspring of non-firefighters. Limited data was available for assessing maternal firefighting outcomes. Future studies should prioritize studies using occupational exposure matrices to limit misclassification of exposure.

Prenatal Parental Exposure to Metals and Birth Defects: A Prospective Birth Cohort Study.

While maternal exposure to high metal levels during pregnancy is an established risk factor for birth defects, the role of paternal exposure remains largely unknown. We aimed to assess the associations of prenatal paternal and maternal metal exposure and parental coexposure with birth defects in singletons. This study conducted within the Jiangsu Birth Cohort recruited couples in early pregnancy. We measured their urinary concentrations for 25 metals. A total of 1675 parent-offspring trios were included. The prevalence of any birth defects among infants by one year of age was 7.82%. Paternal-specific gravity-corrected urinary concentrations of titanium, vanadium, chromium, manganese, cobalt, nickel, copper, and selenium and maternal vanadium, chromium, nickel, copper, selenium, and antimony were associated with a 21-91% increased risk of birth defects after adjusting for covariates. These effects persisted after mutual adjustment for the spouse's exposure. Notably, when assessing the parental mixture effect by Bayesian kernel machine regression, paternal and maternal chromium exposure ranked the highest in relative importance. Parental coexposure to metal mixture showed a pronounced joint effect on the risk of overall birth defects, as well as for some specific subtypes. Our findings suggested a couple-based prevention strategy for metal exposure to reduce birth defects in offspring.

P-584 Occupational paternal risk factors for cryptorchidism and hypospadias in the offspring: a case-control study

Abstract Study question Does paternal occupational exposures to reprotoxic chemical and physical hazards constitute risk factors to cryptorchidism and hypospadias in the offspring? Summary answer Paternal occupational reprotoxic exposures, determined through a job exposure matrix, and paternal rural lifestyle are associated with cryptorchidism, hypospadias, and other genital congenital malformations. What is known already Cryptorchidism and hypospadias are the most common congenital malformations of the male urogenital organs. Over the past century, these congenital malformations, which are associated with testicular cancer and impaired semen quality, have been included into a common disease spectrum known as the testicular dysgenesis syndrome. The association between urogenital congenital malformations and fetal exposure to many factors has been suggested, in particular to genetic and epigenetic factors and environmental factors. There is growing scientific evidence that both maternal and paternal exposure at the time of fertilization play a role after fertilization. Study design, size, duration This is a case-control study with standardized data collection of a 220 father-child cohort recruited from the consultants of our genetic counseling service at the medical university of Sfax (Tunisia), over two years. Participants/materials, setting, methods We compared 110 children diagnosed with congenital malformations to 110 children without any congenital defects. Controls did not differ from the total cohort in confounding variables. Information about paternal jobs held early in pregnancy was collected. Determined via a job exposure matrix, paternal occupational reprotoxic exposures were assessed. Logistic regression analysis was performed to assess the associations between paternal occupational exposures and the congenital testicular dysgenesis syndrome in offspring, including cryptorchidism and hypospadias. Main results and the role of chance 75.54% of children had congenital heart defects and 24.54% of them had genital malformations (n = 27). Paternal occupational exposures to pesticides were associated with the risk of developing birth defects (odds ratio = 17.568 (95% CI), 2.258-136.673). Our results indicate that paternal exposure to pesticides, phthalates, alkylphenolic compounds and other endocrine disruptors was associated with genital and cardiac birth defects. Both cryptorchidism and hypospadias in offspring were associated with paternal rural lifestyle as well as the absence of a maternal job. Limitations, reasons for caution The cohort size in this case-control study may limit the statistical power of the logistical regression to detect associations. Additionally, cases and controls may be selected in a way that does not represent the general population accurately. This can introduce bias and affect the external validity of the study. Wider implications of the findings Including paternal exposures in subsequent investigations of risk factors for cryptorchidism and hypospadias, and further exploring the connection between paternal pesticide exposure and epigenetic alterations, may offer insights into their impact on paternal spermatogenesis, sperm small RNAs, and the potential development of congenital testicular dysgenesis syndrome in future generations. Trial registration number 0400/2022

P-010 Impact of paternal occupational exposures on fetal loss in the female partner: a systematic review

Abstract Study question Are paternal occupational exposures associated with a higher risk of fetal loss in the unexposed female partner? Summary answer Significant positive associations between paternal occupational exposures and fetal loss were retrieved, for chemical and physical agents and for several occupations. What is known already Adverse pregnancy outcomes are frequent and, in its recently updated guidelines, the ESHRE reinforced the interest of exploring the father’s exposures. Nevertheless, causes of fetal loss are still most often investigated only in mothers. Paternal risk factors for fetal loss have been scarcely explored, particularly occupational exposures. Though, males appear to be more exposed to occupational reprotoxic agents than females and are not always aware or sufficiently informed of these exposures. Reprotoxic mechanisms of father’s occupational exposures may include sperm nucleus alteration, seminal fluid contamination and/or indirect exposure of the mother to paternal occupational environment (via linen, dust…). Study design, size, duration A systematic review of the literature using PRISMA 2020 methodology was performed for full text English and French language articles in the Pubmed MEDLINE, Google Scholar, Web of Science and Embase databases. Participants/materials, setting, methods We included only original studies published until December 2022, performed in humans, including a control group and performing a multivariate analysis. The fetal losses analysed were early and/or late and we did not exclude studies analysing stillbirths. We excluded studies in which the female partner was also occupationally exposed. The dose-response relationship and mechanisms of action were noted where described. Main results and the role of chance The 33 studies included analysed a total of 540,246 pregnancies from 8,183 couples or 114,093 exposed male workers, and were classified into 3 groups according to the occupational hazards studied. Regarding chemical agents, the risk of miscarriage was significantly increased in cases of paternal occupational exposure to Thiocarbamate(OR = 1.9, 95% CI 1.1-3.3), Carbaryl (OR = 1.9, 95% CI 1.9-3.1), Dichloro-Diphenyl-Trichloroethane (OR = 1.57, 95% CI 1.13-2.18), printing solvents (OR = 5.5, 95% CI 1.8-17.2), ethylene oxide (OR = 4.7, 95% CI 1.2-18.4), petroleum refinery solvents (OR = 2.2, 95% CI 1.3-3.8) and stainless steel welding fumes (RR = 3.5, 95% CI 1.3-9.1). Regarding physical agents, the risk of stillbirth or perinatal mortality was significantly increased with exposure to ionising (OR = 1.86, 95% CI 1.21-2.76) and nonionising radiation (RR = 2.23, 95% CI 1.08-4.62). Regarding the type of occupation, the risk of miscarriage or stillbirth was significantly increased among crushers, grinders and calenders (OR = 2.20, 95% CI 1.13-4.30), to seamstresses (OR = 2.54, 95% CI 1.29-5), sheet metal workers and commercial aircrew (OR = 2.85, 95% CI 1.30-6.23). The dose-response relationships showed divergent results. The mechanisms of action hypothesized were mainly germ cell mutations. Limitations, reasons for caution The publications selected were mostly published before 2010 and showed high variation in the population sizes, types of male occupational exposure, and in the nature and number of confounding factors used for the multivariate statistical analysis. Due to the various nature of exposures analysed, no meta-analysis could be performed. Wider implications of the findings Men should be made more aware of male-mediated occupational reproductive risks. Occupational health professionals should participate in the investigation of the causes of foetal loss and act on male occupational exposures that may impact pregnancy outcomes. Further high-powered prospective studies are needed, which should include paternal current occupational exposures. Trial registration number not applicable

O-135 The consequences of paternal pre-conceptional health for offspring health and pregnancy outcomes: involvement of the germ-cell epigenome and non-germ cell factors

Abstract Study question Paternal health at conception is important for offspring health. The susceptibility windows within the male reproductive tract and the molecular mechanisms are not completely understood. Summary answer Using mouse genetics, (epi)genomics and in-depth phenotyping, we show that the germ-cell epigenome and components of the seminal fluid are critical for paternal intergenerational effects. What is known already Paternal intergenerational effects are highly conserved across mammals and lower organisms including flies and nematodes. In mammals, the sperm epigenome, as well as the composition of the seminal fluid are sensitive to environmental challenges and influence offspring development and adult phenotypic trajectories. The best known of these mechanisms are DNA methylation and small non-coding RNAs in spermatozoa and the balance between inflammatory and tolerogenic cytokines in the seminal fluid. Small non-coding RNAs are mostly acquired by maturing spermatozoa during the epididymal transit from extracellular vesicle of epididymal epithelial origin, and have the potential to influence embryonic development and offspring health. Study design, size, duration We use two paternal paradigms of pre-conceptional challenge in wild-type C57BL6 mice: high-fat diet feeding for 2 weeks and circadian disruption for 4 weeks before conception. The duration of the environmental challenges has been chosen to meet timing of sperm maturation in the mouse (high-fat diet) or to be the minimum sufficient to induce circadian disruption without overt side effects. Exposed males and their offspring have undergone deep metabolic and molecular phenotyping. Participants/materials, setting, methods We used both bulk and single cell (epi)genomics on exposed males as well as male and female offspring. The molecular phenotyping has been instructed by the results of the metabolic phenotyping performed in collaboration with the German Mouse Clinic, the biggest mouse clinic in Europe, using highly standardized and robust procedures. Importantly, we have used a family-based approach for the data analysis, according to which the experimental n is the exposed father. Main results and the role of chance Paternal circadian disruption achieved by four weeks of day-restricted feeding (food only during the light phase), leads to hyperphagia, hyperglycemia, hypercorticosteronemia and partial circadian disruption in unexposed male offspring. The phenotypes are gender-specific and the females feature partial protection from the paternal effects. Mechanistically, mouse seminal fluid contains corticosterone, whose appearance dynamic follows the organismal circadian rhythm and is blunted upon circadian disruption. Offspring phenotypes are sensitive to the levels of corticosterone in the seminal fluid and consequential to impaired placentation, reduced placental efficiency and fetal growth restriction. Paternal exposure to an acute high-fat diet challenge, instead, leads to a 30% penetrant glucose intolerance phenotype exclusively in male offspring. Mechanistically, this is linked to diet-induced mitochondrial dysfunction in somatic and germ cells and a compensatory burst of mitochondrial DNA transcription in spermatozoa. Mitochondrial DNA encoded small non-coding RNAs accumulate in spermatozoa, are inherited at fertilization, and reprogram early embryo transcription towards premature activation of oxidative metabolism, a predisposing factor to adult-onset glucose intolerance. Importantly, phenotypes and mechanisms are conserved across highly characterized human cohorts. These studies strengthen the importance of paternal health at conception for pregnancy and offspring health and identify germ-cell and non-germ cell factors as potential mechanistic mediators. Limitations, reasons for caution Although we have shown for the first time that stress hormones are present in the seminal fluid and relay paternal stress to the offspring and provided the first example of epigenetic inheritance of sperm small non-coding RNAs, mechanisms are still to be completely uncovered. Complementary mechanisms cannot be excluded. Wider implications of the findings Our findings strengthen the importance of paternal health at conception for pregnancy and offspring health. They also provide potential male tract biomarkers and novel strategies to monitor paternal health at conception and preconception lifestyle interventions aimed at improving pregnancy outcomes and preventing the spread of metabolic disorders through epigenetic inheritance. Trial registration number not applicable

Chronic paternal alcohol exposures induce dose-dependent changes in offspring craniofacial shape and symmetry.

Although dose-response analyses are a fundamental tool in developmental toxicology, few studies have examined the impacts of toxicant dose on the non-genetic paternal inheritance of offspring disease and dysgenesis. In this study, we used geometric morphometric analyses to examine the impacts of different levels of preconception paternal alcohol exposure on offspring craniofacial shape and symmetry in a mouse model. Procrustes ANOVA followed by canonical variant analysis of geometric facial relationships revealed that Low-, Medium-, and High-dose treatments each induced distinct changes in craniofacial shape and symmetry. Our analyses identified a dose threshold between 1.543 and 2.321g/kg/day. Below this threshold, preconception paternal alcohol exposure induced changes in facial shape, including a right shift in facial features. In contrast, above this threshold, paternal exposures caused shifts in both shape and center, disrupting facial symmetry. Consistent with previous clinical studies, changes in craniofacial shape predominantly mapped to regions in the lower portion of the face, including the mandible (lower jaw) and maxilla (upper jaw). Notably, high-dose exposures also impacted the positioning of the right eye. Our studies reveal that paternal alcohol use may be an unrecognized factor contributing to the incidence and severity of alcohol-related craniofacial defects, complicating diagnostics of fetal alcohol spectrum disorders.

Paternal mixed exposure to nicotine/ethanol/caffeine damaged cartilage quality in paternal/offspring rats and its differential glucocorticoid regulation mechanisms

Paternal mixed exposure to nicotine/ethanol/caffeine damaged cartilage quality in paternal/offspring rats and its differential glucocorticoid regulation mechanisms

Patterns of paternal medication dispensation around the time of conception.

Past research on the safety of prenatal exposure to medications has focused on maternal use during gestation, with limited research into the potential effects of paternal use during the spermatogenic period preceding conception. Knowing the most common medications used by fathers around the time of conception can inform research priorities in this field. To identify the most common medications dispensed to fathers in the preconception period. Within the MarketScan research database of commercially insured individuals in the United States from 2011 to 2020, we identified pregnancies, estimated the date of conception, linked each pregnancy to the father using family enrolment information and required minimum enrolment period and prescription benefits. Then, we described the use of prescription medications by the father during the 90 days before conception based on pharmacy dispensation claims. Of 4,437,550 pregnancies, 51.6% were linked with a father. Among the 1,413,762 pregnancies connected with a father that also met the inclusion criteria, the most common classes of medications dispensed were psychotropics (8.66%), antibiotics (7.21%), and analgesics (6.82%). The most frequently dispensed medications were amoxicillin (3.75%), azithromycin (3.15%), fluticasone (2.70%) and acetaminophen/hydrocodone (2.70%). Some fathers filled prescriptions for medications associated with foetal embryopathy when used by the mother, including mycophenolate (0.04%), methotrexate (0.03%) and isotretinoin (0.02%). More than a third of fathers filled at least one prescription medication in the preconception period, and several of them are known to be embryotoxic, emphasizing the necessity for further investigation into the potential teratogenicity of paternal exposure.