Paternal Exposure Research Articles

Sex dependent intergenerational effects of lead in mouse model

Lead (Pb) exposure negatively impacts fertility in both males and females, pregnancy outcomes, and child brain development. We investigated the reproductive and neurological effects of Pb exposure on male and female mice via Pb-contaminated soil for 4 weeks. Breeding was conducted after completion of exposure, in four groups; group 1 consisted of exposed dams and unexposed sires, group 2 consisted of exposed sires and unexposed dams, group 3 consisted of exposed sires and exposed dams and group 4 was the control. Generally, Pb exposure reduced observed conception rates, with a cumulative decrement observed when both males and females are exposed. Gene expression of the testes revealed oxidative stress as the cause of reduced conception rates. Neurological tests: Morris water maze and rotarod were conducted on F1 generation offspring. Maternally and paternally exposed F1 mice performed poorly in the Morris water maze when compared to the control. The severity of the neurological effects was also parent-dependent and sex-dependent. Paternal Pb exposure effects were more pronounced in female offspring. A comparison of gene expression changes of the hippocampus and prefrontal cortex showed paternal Pb-exposure resulted in more prefrontal cortex changes than in the hippocampus, a trend also recorded in the exposed sires. The pronounced effects in female offspring of paternal Pb exposure may suggest that Pb neurological effects may be X-chromosome-linked.

A new perspective on the causal pathway between maternal mental health and neonatal adversity.

Substantial evidence suggests a downstream impact of maternal mental health on birth outcomes. The roles of comorbid maternal physical health and familial confounding underlying this association remain unclear. This cohort study included a random sample of children born 1997-2008 within a health maintenance organization (HMO) in Israel, their parents, and siblings. Outcomes were ICD-9 diagnoses of neonatal adversities (birth complications and congenital anomalies) and exposures were maternal diagnoses of mental health disorders. Odds ratios (ORs) and their 95% confidence intervals for the associations between maternal mental health diagnoses and measures of neonatal adversity were calculated using logistic regression, adjusting for maternal age, child's year of birth, socioeconomic status, and maternal physical morbidity burden. We examined potential familial confounding using a negative control approach based on paternal exposure. In our sample of 74,533 children, 6,674 (9.1%) were born after birth complications and 14,569 (19.9%) with a congenital anomaly. Maternal mental health diagnosis around pregnancy was significantly associated with these measures of neonatal adversity after adjustment for potential confounders (birth complications: OR = 1.3 (1.2-1.4), p < 0.001; congenital anomalies: OR = 1.2 (1.1-1.3), p < 0.001). These associations became attenuated and non-significant after further adjustment for maternal physical morbidity burden. In a joint model, maternal and paternal diagnosis of a mental health disorder were independently associated with neonatal adversity (birth complications: ORmat=1.3 (1.1-1.4), p < 0.001; ORpat=1.2 (1.1-1.3), p = 0.004; congenital anomalies: ORmat=1.2 (1.1-1.3), p < 0.001; ORpat=1.1 (1.0-1.2), p = 0.01). Physical health and familial factors play a role in the associations between maternal mental health and neonatal adversity.

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.

Residential Environment and Parental Lifestyle as Risk Factors of The Co-Occurrence of Cleft Lip and Palate Birth Defect Cases in Indonesia

Cleft lip and palate (CLP) are multifactorial birth defects, and the etiology behind their occurrence remains insufficiently understood. This case-control study aimed to investigate the association between residential environmental factors, parental lifestyle, and the risk of CLP in Indonesia. A total of 213 participants from 14 provinces were selected using stratified random sampling. Multivariable logistic regression was employed to determine the odds ratios (ORs) with 95% confidence intervals (CIs) for each risk factor. The study identified significant associations between several residential environmental factors and CLP. Proper kitchen ventilation was found to be protective (OR = 0.245, 95% CI: 0.096–0.624, p = 0.003), while proximity to industrial sites significantly increased the risk (OR = 3.595, 95% CI: 1.029–12.558, p = 0.045). Additionally, using treated drinking water showed a protective effect (OR = 0.39, 95% CI: 0.16–0.95, p = 0.038), whereas concerns about water sources displayed a marginally significant risk increase (OR = 2.841, 95% CI: 0.876–9.211, p = 0.082). Regarding parental lifestyle factors, maternal active smoking exhibited a marginal protective association (OR = 0.052, 95% CI: 0.002–1.09, p = 0.057), while paternal passive smoking presented a marginally significant risk (OR = 2.309, 95% CI: 0.897–5.942, p = 0.083). Furthermore, paternal radiation exposure was associated with an elevated risk of CLP (OR = 3.489, 95% CI: 0.828–14.703, p = 0.089). These findings highlight the need for targeted public health interventions to mitigate environmental exposures and promote safer parental lifestyle behaviors in Indonesia.

Air pollution exposure in vitrified oocyte donors and male recipient partners in relation to fertilization and embryo quality

BackgroundStudies on air pollution and outcomes of in vitro fertilization (IVF) have focused on couples undergoing autologous IVF, in which it is challenging to disentangle maternal and paternal exposures during gametogenesis. We sought to evaluate the independent associations between air pollution exposure during oogenesis and spermatogenesis on fertilization and embryo quality in non-identified donor oocyte IVF cycles. MethodsOur study included 500 oocyte donors and 915 male recipient partners who contributed 1,095 oocyte thaw cycles (2008–2019). Daily ambient air pollutant exposure was estimated using spatio-temporal models based on residential address and averaged over folliculogenesis (i.e., three months prior to initiation of controlled ovarian stimulation), controlled ovarian stimulation, and spermatogenesis (i.e., 72 days prior to oocyte thaw). We used multivariable generalized estimating equations to estimate the adjusted odds ratios (aOR) and 95 % confidence intervals (CI) for an interquartile range increase in pollutant exposure in relation to the proportion of oocytes surviving thaw, oocytes fertilized, and usable embryos. ResultsOocyte donors with higher exposure to organic carbon (OC) (aOR = 0.86 95 %CI 0.79,0.94) and particulate matter < 10 µm (aOR = 0.69 95 %CI 0.54,0.90) during folliculogenesis had a lower proportion of oocytes surviving thaw. During ovarian stimulation, higher particulate matter < 2.5 µm (aOR = 0.78 95 %CI 0.66, 0.91), nitrate (aOR = 0.83 95 % CI 0.69,0.99), and OC (aOR = 0.86 95 % CI 0.80,0.93) exposure was associated with a lower proportion of surviving oocytes while nitrogen dioxide (aOR = 1.11 95 %CI 1.00,1.23) and ozone (aOR = 1.19 95 %CI 1.04,1.37) exposure was associated with a higher proportion of fertilized oocytes and usable embryos. Elemental carbon (aOR = 0.93 95 %CI 0.87,1.00) and OC (aOR = 0.95 95 %CI 0.90,1.00) exposure during spermatogenesis was associated with a slightly lower proportion of usable embryos. On the day of oocyte thaw, higher ambient OC at the IVF clinic was associated with lower oocyte survival and higher ozone was associated with lower fertilization. ConclusionsBoth maternal and paternal air pollution exposures during gametogenesis have independent, largely detrimental, effects on early embryological outcomes.

Associations of maternal and paternal preconception and maternal pregnancy urinary phthalate biomarker and bisphenol A concentrations with offspring autistic behaviors: The PEACE study

BackgroundEnvironmental chemical exposures in utero may play a role in autism development. While preconception risk factors for autism are increasingly being investigated, little is known about the influence of chemical exposures during the preconception period, particularly for paternal exposures. MethodsIn 195 children from the Preconception Environmental exposures And Childhood health Effects (PEACE) cohort born to parents recruited from a fertility clinic in Boston, Massachusetts between 2004 and 2017, we quantified concentrations of 11 phthalate metabolites and bisphenol A (BPA) in urine samples collected from mothers and fathers before conception and mothers throughout pregnancy. When children were 6–15 years old, parents completed the Social Responsiveness Scale (SRS) questionnaire assessing autistic behaviors. We used linear mixed effect models to estimate covariate-adjusted associations of phthalate biomarker and BPA concentrations, separately for maternal preconception (n = 179), paternal preconception (n = 121), and maternal pregnancy (n = 177), with SRS T-scores, based on age and gender, in offspring. We used quantile g-computation models for mixture analyses and evaluated modification by selected dietary factors. ResultsThe mean SRS T-score was 47.7 (±7.4), lower than the normative mean of 50. In adjusted models for individual biomarkers or mixtures, few associations were observed and estimates were generally negative (e.g., lower SRS T-scores) and imprecise. We observed associations of higher mono-isobutyl phthalate (MiBP) concentrations measured in maternal preconception and paternal preconception periods with lower SRS T-scores (βmaternal_precon = −1.6, 95% CI -2.7; −0.4; βpaternal_precon = −2.9, 95% CI -4.6; −1.2) for each loge increase. In a subset of participants with maternal preconception nutrition information, we generally observed stronger inverse associations with higher folate and iron intake, particularly for folate intake and MiBP concentrations. ConclusionsUrinary phthalate biomarker and BPA concentrations during preconception (maternal and paternal) and pregnancy (maternal) were not associated with adverse autistic behaviors in these children. Larger studies are needed to elucidate the observed associations, while considering interactions between maternal nutrition and chemical exposures.

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