Autism placenta

BACKGROUND: Polychlorinated biphenyls (PCBs), extensively used in various products, prompt ongoing concern despite reduced exposure since the 1970s. This systematic review explores prenatal PCB and hydroxylated metabolites (OH-PCBs) exposure's association with child neurodevelopment. Encompassing cognitive, motor development, behavior, attention, ADHD, and ASD risks, it also evaluates diverse methodological approaches in studies. METHODS: PubMed, Embase, PsycINFO, and Web of Science databases were searched through August 23, 2023, by predefined search strings...

Exposure to air pollutants has been associated with adverse health outcomes in adults and children who were prenatally exposed. In addition to reducing exposure to air pollutants, it is important to identify their biologic targets in order to mitigate the health consequences of exposure. One molecular change associated with prenatal exposure to air pollutants is DNA methylation (DNAm), which has been associated with changes in placenta and cord blood tissues at birth. However, little is known about how air pollution exposure impacts the sperm epigenome, which could provide important insights into the mechanism of transmission to offspring...

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according to data from the World Health Organization (WHO). To be diagnosed with ASD, the child must have persistent deficits in communication and social interactions, and restricted and repetitive patterns of behavior, interests, or activities. Despite its prevalence, the etiology of ASD is still uncertain, with multifactorial characteristics, including those associated with the gestational period, where maternal exposure to biological, chemical, or physical hazards occurs, some of which have already been proposed as causes of ASD outcomes...

Perfluorooctanesulfonic acid (PFOS) is a neurotoxic widespread organic contaminant which affects several brain functions including memory, motor coordination and social activity. PFOS has the ability to traverse the placenta and the blood brain barrier (BBB) and cause weight gain in female mice. It's also known that obesity and consumption of a high fat diet have negative effects on the brain, impairs cognition and increases the risk for the development of dementia. The combination effect of developmental exposure to PFOS and the intake of a high-fat diet (HFD) has not been explored...

Gestational exposure to the anticonvulsant drug valproic acid (VPA) is associated with congenital malformations and neurodevelopmental disorders through its action as a histone deacetylase inhibitor. VPA can elicit placental toxicity and affect placental growth and development. The objective of this study was to evaluate the impact of maternal exposure to VPA on the mouse placenta following exposure on gestational day (GD) 13 since previous studies have shown that mice exposed at this time during gestation give birth to offspring with an autism spectrum disorder-like phenotype...

Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts...

Maternal immune activation (MIA) during pregnancy increases the risk for the unborn foetus to develop neurodevelopmental conditions such as autism spectrum disorder and schizophrenia later in life. MIA mouse models recapitulate behavioural and biological phenotypes relevant to both conditions, and are valuable models to test novel treatment approaches. Selenium (Se) has potent anti-inflammatory properties suggesting it may be an effective prophylactic treatment against MIA. The aim of this study was to determine if Se supplementation during pregnancy can prevent adverse effects of MIA on offspring brain and behaviour in a mouse model...

Autism Spectrum Disorder (ASD) is a synaptic disorder with a GABA/glutamate imbalance in the perineuronal nets and structural abnormalities such as increased dendritic spines and decreased long distance connections. Specific pregnancy disorders significantly increase the risk for an ASD phenotype such as preeclampsia, preterm birth, hypoxia phenomena, and spontaneous miscarriages. They are associated with defects in the glycosylation-immune placental processes implicated in neurogenesis. Some glycans epitopes expressed in the placenta, and specifically in the extra-villous trophoblast also have predominant functions in dendritic process and synapse function...

Global health efforts have increased against infectious diseases, but issues persist with pathogens like Group B Streptococcus (GBS). Preclinical studies have elaborated on the mechanistic process of GBS-induced chorioamnionitis and its impact on the fetal programming of chronic neuropsychiatric diseases. GBS inoculation in rodents demonstrated the following: (i) silent and self-limited placental infection, similar to human chorioamnionitis; (ii) placental expression of chemokines attracting polymorphonuclear (PMN) cells; (iii) in vitro cytokine production; (iv) PMN infiltration in the placenta (histologic hallmark of human chorioamnionitis), linked to neurobehavioral impairments like cerebral palsy and autism spectrum disorders (ASD); (v) upregulation of interleukin-1β (IL-1β) in the placenta and fetal blood, associated with higher ASD risk in humans; (vi) sex-specific effects, with higher IL-1β release and PMN recruitment in male placenta; (vii) male offspring exhibiting ASD-like traits, while female offspring displayed attention deficit and hyperactivity disorder (ADHD)-like traits; (viii) IL-1 and/or NF-kB blockade alleviate placental and fetal inflammation, as well as subsequent neurobehavioral impairments...

Autism spectrum disorders (ASD) are polygenic multifactorial disorders influenced by environmental factors. ASD-related differential DNA methylation has been found in human peripheral tissues, such as placenta, paternal sperm, buccal epithelium, and blood. However, these data lack direct comparison of DNA methylation levels with brain tissue from the same individual to determine the extent that peripheral tissues are surrogates for behavior-related disorders. Here, whole genome methylation profiling at all the possible sites throughout the mouse genome (>25 million) from both brain and blood tissues revealed novel insights into the systemic contributions of DNA methylation to ASD...

Maternal immune activation (MIA) during pregnancy is linked to neurodevelopmental disorders in humans. Similarly, the TLR7 agonist imiquimod alters neurodevelopment in rodents. While the mechanisms underlying MIA-mediated neurodevelopmental changes are unknown, they could involve dysregulation of amino acid transporters essential for neurodevelopment. Therefore, we sought to determine the nature of such transporter changes in both imiquimod-treated rats and human placentas during infection. Pregnant rats received imiquimod on gestational day (GD)14...

Autism is more prevalent in males and males on average score higher on measures of autistic traits. Placental function is affected significantly by the sex of the fetus. It is unclear if sex differences in placental function are associated with sex differences in the occurrence of autistic traits postnatally. To assess this, concentrations of angiogenesis-related markers, placental growth factor (PlGF) and soluble fms-like tyrosine kinase (sFlt-1) were assessed in maternal plasma of expectant women in the late 1st (mean= 13...

BACKGROUND: With the growing availability of cannabis and the popularization of additional routes of cannabis use beyond smoking, including edibles, the prevalence of cannabis use in pregnancy is rapidly increasing. However, the potential effects of prenatal cannabis use on fetal developmental programming remain unknown. RESULTS: We designed this study to determine whether the use of edible cannabis during pregnancy is deleterious to the fetal and placental epigenome...

Inflammation contributes to numerous neuropsychiatric disorders, especially those that first appear in childhood. Maternal intrauterine environment, including the placenta, has a role in brain development and risk for neuropsychiatric disorders. This study examines the link between fetal inflammatory syndrome (FIRS), which is placental inflammation in the peri-partem period, and neuropsychiatric disorders during childhood.This is a retrospective cohort study using data from electronic medical records over a 19-year period at one women's hospital...

BACKGROUND: Autism likelihood is a largely heritable trait. Autism prevalence has a skewed sex ratio, with males being diagnosed more often than females. Steroid hormones play a mediating role in this, as indicated by studies of both prenatal biology and postnatal medical conditions in autistic men and women. It is currently unclear if the genetics of steroid regulation or production interact with the genetic liability for autism. METHODS: To address this, two studies were conducted using publicly available datasets, which focused respectively on rare genetic variants linked to autism and neurodevelopmental conditions (study 1) and common genetic variants (study 2) for autism...

Maternal immune activation (MIA) by environmental challenges is linked to severe developmental complications, such as neurocognitive disorders, autism, and even fetal/maternal death. Benzene is a major toxic compound in air pollution that affects the mother as well as the fetus and has been associated with reproductive complications. Our objective was to elucidate whether benzene exposure during gestation triggers MIA and its impact on fetal development. We report that benzene exposure during pregnancy leads MIA associated with increased fetal resorptions, fetal growth, and abnormal placenta development...

Recent experimental and observational research has suggested that childhood allergic asthma and other conditions may be the result of prenatal exposure to environmental contaminants, such as di-(2-ethylhexyl) phthalate (DEHP). In a previous epidemiological study, we found that ancestral exposure (F0 generation) to endocrine disruptors or the common plasticizer DEHP promoted allergic airway inflammation via transgenerational transmission in mice from generation F1 to F4. In the current study, we employed a MethylationEPIC Beadchip microarray to examine global DNA methylation in the human placenta as a function of maternal exposure to DEHP during pregnancy...

Mercury is a toxic metal which can cross the placenta and the blood-brain barrier and cause the disruption of various cellular processes. Studies have investigated mercury exposure and neurodevelopmental disorders; therefore, a critical and rigorous analysis of this evidence is required. The objective of this review was to evaluate the available scientific evidence on the effects of mercury exposure during the prenatal and postnatal periods and its relationship with the development of neurobehavioral disorders...

BACKGROUND: Assisted reproductive technologies (ART) may perturb DNA methylation (DNAm) in early embryonic development. Although a handful of epigenome-wide association studies of ART have been published, none have investigated CpGs on the X chromosome. To bridge this knowledge gap, we leveraged one of the largest collections of mother-father-newborn trios of ART and non-ART (natural) conceptions to date to investigate sex-specific DNAm differences on the X chromosome. The discovery cohort consisted of 982 ART and 963 non-ART trios from the Norwegian Mother, Father, and Child Cohort Study (MoBa)...

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) characterized by impairments in social communication, repetitive behaviors, restricted interests, and hyperesthesia/hypesthesia caused by genetic and/or environmental factors. In recent years, inflammation and oxidative stress have been implicated in the pathogenesis of ASD. In this review, we discuss the inflammation and oxidative stress in the pathophysiology of ASD, particularly focusing on maternal immune activation (MIA). MIA is a one of the common environmental risk factors for the onset of ASD during pregnancy...