Sex and gender bias in the experimental neurosciences: the case of the maternal immune activation model.
Ontology highlight
ABSTRACT:
SUBMITTER: Coiro P
PROVIDER: S-EPMC6375995 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Infections during gestation and the consequent maternal immune activation (MIA) increase the risk of developing neuropsychiatric disorders in infants and throughout life, including autism spectrum disorders (ASD). ASD is a neurodevelopmental disorder that affects three times more males than females and is mainly characterized by deficits in social communication and restricted interests. Consistent findings also indicate that ASD patients suffer from movement disorders, although these symptoms are not yet considered as diagnosis criteria. Here we used the double-stranded RNA analog polyinosinic:polycytidylic acid (poly I:C) MIA animal model of ASD in mice and explored its effects in males and females on social and motor behavior. We then investigated brain areas implicated in controlling and coordinating movements, namely the nigro-striatal pathway, motor cortex and cerebellum. We show that male mice are more affected by this treatment than females as they show reduced social interactions as well as motor development and coordination deficits. Reduced numbers of Purkinje cells in the cerebellum was found more widespread and within distinct lobules in males than in females. Moreover, a reduced number of neurons was found in the motor cortex of males only. These results suggest that females are better protected against developmental insults leading to ASD symptoms in mice. They also point to brain areas that may be targeted to better manage social and motor consequences of ASD.
| S-EPMC6438965 | biostudies-literature
Project description:Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.
| S-EPMC4128679 | biostudies-literature
Project description:Importance:Previous studies demonstrate sex bias in surgical research. Female participants and investigators are underrepresented in surgical scientific research. Objectives:To describe the distribution of male and female authors in 5 general-interest surgery journals, assess the association of author gender with sex bias, and explore whether investigators benefit from performing sex-inclusion research. Design, Setting, and Participants:For this bibliometric analysis, data were abstracted from 1921 original, peer-reviewed articles published from January 1, 2011, through December 31, 2012, in Annals of Surgery, American Journal of Surgery, JAMA Surgery, The Journal of Surgical Research, and Surgery. Excluded articles pertained to a sex-specific disease or did not report the number of study participants. An additional 119 articles contained gender-ambiguous author names and were omitted. Data were analyzed from April to June 2017. Main Outcomes and Measures:Male and female first and senior authors, number of female and male participants in each study, surgical specialty, and number of citations received per article. Results:Of the 3604 authors of 1802 articles included in this study, 2791 first and senior authors (77.4%) were male and 813 (22.6%) were female. The prevalence of male and female authors was consistent across all 5 journals and among clinical and basic science research. Articles by female authors included a higher median number of female study participants compared with their male counterparts (27.5 vs 16.0; P?=?.01), but sex matched the inclusion of participants less frequently (36% vs 45%; P?=?.001). No sex-based differences occurred between male and female authors in reporting, statistical analysis, and discussion of the data or in the number of citations received. Compared with studies that did not report, analyze, or discuss data by sex, studies that performed sex-specific data reporting yielded a mean of 2.8 more citations (95% CI, 1.2-4.4; P?=?.001); those that performed statistical analysis, a mean of 3.5 more citations (95% CI, 1.8-5.1; P?=?.001); and those that discussed the data, a mean of 2.6 more citations (95% CI, 0.7-4.5; P?=?.001). Articles with a higher percentage of sex matching of participants also received more citations, with an increase of 1 citation per 4.8% (95% CI, 2.0%-7.7%; P?=?.001) increase in percentage of sex matching. Conclusions and Relevance:Sex bias in surgical research is prevalent among male and female authors; however, female authors included proportionally more female participants in their studies compared with male authors. Notably, studies that addressed sex bias were rewarded by the scientific community with increased citations of their published work.
| S-EPMC5875386 | biostudies-literature
Project description:The etiology of major neurodevelopmental disorders such as schizophrenia and autism is unclear, with evidence supporting a combination of genetic factors and environmental insults, including viral infection during pregnancy. Here we utilized a mouse model of maternal immune activation (MIA) with the viral mimic PolyI:C infection during early gestation. We investigated the transcriptional changes in the brains of mouse fetuses following MIA during the prenatal period, and evaluated the behavioral and biochemical changes in the adult brain. The results reveal an increase in RNA editing levels and dysregulation in brain development-related gene pathways in the fetal brains of MIA mice. These MIA-induced brain editing changes are not observed in adulthood, although MIA-induced behavioral deficits are observed. Taken together, our findings suggest that MIA induces transient dysregulation of RNA editing at a critical time in brain development.
| S-EPMC7567798 | biostudies-literature
Project description:The aim of the study was to explore the nature of the gender-congruency effect, characterized by a facilitation on the processing of congruent words in grammatical gender. Moreover, we explored whether resemblances between gender identities and gender attitudes with grammatical gender modulated lexical processing. We designed a gender-priming paradigm in Spanish, in which participants decided the gender of a masculine or feminine pronoun preceded by three different primes: biological gender nouns (mapping biological sex), stereotypical nouns (mapping biological and stereotypical information), and epicene nouns (arbitrary gender assignment). We found faster processing of gender congruent pronouns independently of the type of prime, showing that the grammatical gender feature is active even when processing bare nouns that are not conceptually related to gender. This indicates that the gender-congruency effect is driven by the activation of the gender information at the lexical level, which is transferred to the semantic level. Interestingly, the results showed an asymmetry for epicene primes: the gender-congruency effect was smaller for epicene primes when preceding the feminine pronoun, probably driven by the grammatical rule of the masculine being the generic gender. Furthermore, we found that masculine oriented attitudes can bias language processing diminishing the activation of feminine gender, which ultimately could overshadow the female figure.
| S-EPMC10242114 | biostudies-literature
Project description:Males have a bias toward developing sputum smear-positive pulmonary tuberculosis, whereas other forms of the disease have an equal sex ratio. Immune responses are known to be affected by estrogen and testosterone. Biomarkers may therefore be affected by these hormones, especially between 16 and 45 years of age when the differences are most marked. Using large data sets, we examined whether the male bias was significant in terms of diagnosis or predictive ability for the development of disease in those exposed to tuberculosis. Despite the large numbers, the need to specify homogeneous population groups for analysis affected the statistical power to discount a useful biomarker. In general, males showed higher interferon-gamma responses to TB antigens ESAT-6 and CFP-10, whilst females had stronger tuberculin responses in those with sputum smear- and culture-positive tuberculosis, but smaller responses in those who were screened for tuberculosis and who did not develop disease. Importantly, in contacts of sputum smear-positive pulmonary tuberculosis, more males who did not develop tuberculosis had tuberculin skin tests in the range between 10 and 14 mm, suggesting that sex-specific cut-offs might be better than general cut-off values for determining who should receive preventive treatment. Immunocytochemistry of the tuberculin responses correlated with cell numbers only in females. Total and anti-lipoarabinomannan IgM antibody levels were lower in males, whereas total and anti-BCG IgE antibody levels were higher. Evaluation of biomarkers should take account of the spectrum of tuberculosis and male sex bias for sputum smear-positive pulmonary tuberculosis. These findings improve our understanding of how immune responses contribute to the pathogenesis of infectious tuberculosis as well as suggesting clinical applications of the differences between the sexes.
| S-EPMC8007857 | biostudies-literature
Project description:This paper contributes to the debate on race- and gender-based discrimination in grading. We apply a quasi-experimental research design exploiting a shift from open grading in 2018 (examinee's name clearly visible on written assignments), to blind grading in 2019 (only student ID number visible). The analysis thus informs name-based stereotyping and discrimination, where student ethnicity and gender are derived from their names on written assignments. The case is a quantitative methods exam at Roskilde University (Denmark). We rely on OLS regression models with interaction terms to analyze whether blind grading has any impact on the relative grading differences between the sexes (female vs. male examinees) and/or between the two core ethnic groups (ethnic minorities vs. ethnic majority examinees). The results show no evidence of gender or ethnic bias based on names in the grading process. The results were validated by several checks for robustness. We argue that the weaker evidence of ethnic discrimination in grading vis-à-vis discrimination in employment and housing suggests the relevance of gauging the stakes involved in potentially discriminatory activities.
| S-EPMC8297848 | biostudies-literature
Project description:The prolonged and sex-dependent impact of maternal immune activation (MIA) during gestation on the molecular pathways of the amygdala, a brain region that influences social, emotional, and other behaviors, is only partially understood. To address this gap, we investigated the effects of viral-elicited MIA during gestation on the amygdala transcriptome of pigs, a species of high molecular and developmental homology to humans. Gene expression levels were measured using RNA-Seq on the amygdala for 3-week-old female and male offspring from MIA and control groups. Among the 403 genes that exhibited significant MIA effect, a prevalence of differentially expressed genes annotated to the neuroactive ligand-receptor pathway, glutamatergic functions, neuropeptide systems, and cilium morphogenesis were uncovered. Genes in these categories included corticotropin-releasing hormone receptor 2, glutamate metabotropic receptor 4, glycoprotein hormones, alpha polypeptide, parathyroid hormone 1 receptor, vasointestinal peptide receptor 2, neurotensin, proenkephalin, and gastrin-releasing peptide. These categories and genes have been associated with the MIA-related human neurodevelopmental disorders, including schizophrenia and autism spectrum disorders. Gene network reconstruction highlighted differential vulnerability to MIA effects between sexes. Our results advance the understanding necessary for the development of multifactorial therapies targeting immune modulation and neurochemical dysfunction that can ameliorate the effects of MIA on offspring behavior later in life.
| S-EPMC7431923 | biostudies-literature
Project description:Niemann-Pick disease, type C1 (NPC1) is a rare neurodegenerative lysosomal storage disease with a wide spectrum of clinical manifestation. Multiple genetic factors influence the NPC1 mouse phenotype, but very little attention has been given to prenatal environmental factors that might have long-term effects on the neuroinflammatory component of NPC1 pathology. Studies in other mouse models of cerebellar ataxia have shown that developmental exposures lead to Purkinje neuron degeneration later in life, suggesting that environmental exposures during development can impact cerebellar biology. Thus, we evaluated the potential effect of maternal immune activation (MIA) on disease progression in an Npc1 mouse model. The MIA paradigm used mimics viral infection using the toll like receptor 3 agonist polyinosinic-polycytidilic acid during gestation. Through phenotypic and pathologic tests, we measured motor and behavioral changes as well as cerebellar neuroinflammation and neurodegeneration. We observed a gender and genotype dependent effect of MIA on the cerebellum. While the effects of MIA have been previously shown to primarily affect male progeny, we observed increased sensitivity of female mutant progeny to prenatal exposure to treatment with polyinosinic-polycytidilic acid. Specifically, prenatal MIA resulted in female NPC1 mutant progeny with greater motor deficits and a corresponding decrease in cerebellar Purkinje neurons. Our data suggest that prenatal environmental exposures may be one factor contributing to the phenotypic variability observed in individuals with NPC1.
| S-EPMC7002177 | biostudies-literature
Project description:Maternal immune activation (MIA)puts offspring at greater risk for neurodevelopmental disorders associated with impaired social behavior. While it is known that immune signaling through the maternal, placental, and fetal compartments contribute to these phenotypical changes, it is unknown to what extent the stress response to illness is involved and how it can be harnessed for potential interventions. To this end, pregnant rat dams were treated with the clinically available 11β-hydroxylase inhibitor metyrapone, alongside administration of the bacterial mimetic lipopolysaccharide (LPS), on gestational day 15. Maternal, placental, and fetal CNS levels of corticosterone and placental 11ßHSD enzymes type 1 and 2 were measured 3-hrs post treatment. Subsequently, offspring social behaviors were measured across critical phases of development. MIA was associated with increased maternal, placental, and fetal CNS corticosterone concentrations that were diminished with metyrapone exposure. Metyrapone protected against reductions in placental 11ßHSD2 in males only, suggesting that less corticosterone was inactivated in female placentas. Behaviorally, metyrapone-exposure protected against MIA-induced social disruptions in juvenile, adolescent, and adult males, while females were unaffected or performed worse. Transcriptomic analyses revealed that metyrapone-exposure triggered opposing effects on gene expression to combat MIA-exposure in males, but not among females. Taken together, these findings illustrate that MIA-induced HPA responses act alongside the immune system to produce behavioral deficits. As a clinical drug already provided to pregnant people and neonates for the treatment of hypercortisolism, the sex-specific benefits and constraints of metyrapone should be investigated further as a potential means of reducing neurodevelopmental risks due to gestational MIA.
2023-08-15 | GSE240604 | GEO