, Jieun Jang, Nayoung Kim Citations
, Eunha Kim Neurodevelopmental disorders, which emerge early in development, include a range of neurological phenotypes and exhibit marked differences in prevalence between sexes. A male predominance is particularly pronounced in autism spectrum disorder (ASD). Although the precise cause of ASD is still unknown, certain genetic variations and environmental influences have been implicated as risk factors. Preclinical ASD models have been instrumental in shedding light on the mechanisms behind the sexual dimorphism observed in this disorder. In this review, we explore the potential processes contributing to sex bias by examining both intrinsic differences in neuronal mechanisms and the influence of external factors. We organize these mechanisms into six categories: 1) sexually dimorphic phenotypes in mice with mutations in ASD-associated genes related to synaptic dysfunction; 2) sex-specific microglial activity, which may disrupt neural circuit development by excessively pruning synapses during critical periods; 3) sex steroid hormones, such as testosterone and allopregnanolone, that differentially influence brain structure and function; 4) escape from X chromosome inactivation of the O-linked-N-acetylglucosamine transferase gene in the placenta; 5) sexually dimorphic activation of the integrated stress response pathway following maternal immune activation; and 6) immunological responses that are differentially regulated by sex. Understanding these mechanisms is essential for deciphering the underlying causes of ASD and may offer insights into other disorders with notable sex disparities.
, Won Kim Understanding the effects of sex and sex differences on liver health and disease is crucial for individualized healthcare and informed decision-making for patients with liver disease. The impact of sex on liver disease varies according to its etiology. Women have a lower prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) than men. However, postmenopausal women face a higher risk of advanced liver fibrosis due to hormonal influences. Sex differences affect the pathogenesis of MASLD, which involves a complex process involving several factors such as hormones, obesity, and the gut microbiome. Furthermore, sex-related differences in the development of MASLDrelated hepatocellular carcinoma have been observed. The sex-specific characteristics of MASLD necessitate an individualized management approach based on scientific evidence. However, research in this area has been lacking. This article reviews the current understanding of sex differences in MASLD.
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, Heisook Lee This review aims to highlight the importance of research on structural, functional, molecular-biological, and disease-specific sex differences in the brain, and to examine current bibliometric indicators related to research on sex differences. The Web of Science Core Collection was searched for related articles from 2010 to 2023. Structural and functional brain differences according to sex, including variations in communication patterns between hemispheres, may play a role in mental disorders. Sex differences in neurotransmitters such as serotonin, dopamine, and γ-aminobutyric acid contribute to disparities in mental health, addiction, and neurodevelopmental conditions. Neurodevelopmental disorders such as autism spectrum disorder and schizophrenia exhibit sex-based differences in prevalence, symptoms, brain changes, and neurotransmitter disruptions under hormonal influence. There is a growing body of research on depression, adolescence, the hippocampus, the amygdala, and cognition, highlighting the importance of considering sex/gender factors. Recent studies on sex differences in brain diseases have identified variations in brain structure, function, and neurophysiological substances, as well as in hormones and genes between the sexes. The incidence of psychiatric disorders such as autism spectrum disorder, depression, anxiety, and Alzheimer’s disease is increasingly being linked to sex differences, and the need for research into the mechanisms underlying these differences is gaining recognition. However, there remains a significant gap in sex-specific neuroscience research related to the diagnosis, treatment, prevention, and management of these conditions. Advancing inclusive research will require comprehensive training, a consensus on methodology, diverse perspectives through collaborative frameworks, governmental/institutional support, and dedicated funding to create suitable research environments and implementation strategies.
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Heart failure (HF) represents a serious public health concern, characterized by substantial morbidity and mortality. Despite advances in pharmacological management, a gap persists in understanding and accounting for sex-related differences in HF treatment. This review was performed to clarify the impact of sex on the clinical outcomes of HF medications. Insights from various clinical trials and studies have highlighted differences between men and women in drug responses and adverse effects, indicating the need for a more nuanced approach to HF management. Promoting greater representation of women in clinical trials and the development of research methodologies that consider sex differences are crucial steps in advancing precision medicine. Such efforts ensure that therapeutic strategies are optimally tailored to the unique biological and genetic profiles of each person. Ultimately, this review emphasizes the vital need for a more inclusive and personalized approach to HF pharmacotherapy, underscoring the critical role of sex-related differences in shaping effective and individualized treatment pathways.
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