Sex Differences Research Articles

Sex differences in the distribution and density of regulatory interneurons in the striatum

IntroductionDysfunction of the cortico-basal circuitry – including its primary input nucleus, the striatum – contributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons.MethodsWe use stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice.ResultsMales have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences.DiscussionThese sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

Sex differences in the distribution and density of regulatory interneurons in the striatum

IntroductionDysfunction of the cortico-basal circuitry – including its primary input nucleus, the striatum – contributes to neuropsychiatric disorders, such as autism and Tourette Syndrome (TS). These conditions show marked sex differences, occurring more often in males than in females. Regulatory interneurons, such as cholinergic interneurons (CINs) and parvalbumin-expressing GABAergic fast spiking interneurons (FSIs), are implicated in human neuropsychiatric disorders such as TS, and ablation of these interneurons produces relevant behavioral pathology in male mice, but not in females. Here we investigate sex differences in the density and distribution of striatal interneurons.MethodsWe use stereological quantification of CINs, FSIs, and somatostatin-expressing (SOM) GABAergic interneurons in the dorsal striatum (caudate-putamen) and the ventral striatum (nucleus accumbens) in male and female mice.ResultsMales have a higher density of CINs than females, especially in the dorsal striatum; females have equal distribution between dorsal and ventral striatum. FSIs showed similar distributions, with a greater dorsal-ventral density gradient in males than in females. SOM interneurons were denser in the ventral than in the dorsal striatum, with no sex differences.DiscussionThese sex differences in the density and distribution of FSIs and CINs may contribute to sex differences in basal ganglia function, particularly in the context of psychopathology.

Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis.

Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

Sex differences in motor learning flexibility are accompanied by sex differences in mushroom spine pruning of the mouse primary motor cortex during adolescence

BackgroundAlthough males excel at motor tasks requiring strength, females exhibit greater motor learning flexibility. Cognitive flexibility is associated with low baseline mushroom spine densities achieved by pruning which can be triggered by α4βδ GABAA receptors (GABARs); defective synaptic pruning impairs this process.MethodsWe investigated sex differences in adolescent pruning of mushroom spine pruning of layer 5 pyramidal cells of primary motor cortex (L5M1), a site essential for motor learning, using microscopic evaluation of Golgi stained sections. We assessed α4GABAR expression using immunohistochemical and electrophysiological techniques (whole cell patch clamp responses to 100 nM gaboxadol, selective for α4βδ GABARs). We then compared performance of groups with different post-pubertal mushroom spine densities on motor learning (constant speed) and learning flexibility (accelerating speed following constant speed) rotarod tasks.ResultsMushroom spines in proximal L5M1 of female mice decreased &amp;gt;60% from PND35 (puberty onset) to PND56 (Pubertal: 2.23 ± 0.21 spines/10 μm; post-pubertal: 0.81 ± 0.14 spines/10 μm, P &amp;lt; 0.001); male mushroom spine density was unchanged. This was due to greater α4βδ GABAR expression in the female (P &amp;lt; 0.0001) because α4 -/- mice did not exhibit mushroom spine pruning. Although motor learning was similar for all groups, only female wild-type mice (low mushroom spine density) learned the accelerating rotarod task after the constant speed task (P = 0.006), a measure of motor learning flexibility.ConclusionsThese results suggest that optimal motor learning flexibility of female mice is associated with low baseline levels of post-pubertal mushroom spine density in L5M1 compared to male and female α4 -/- mice.

Sex differences in treatment of familial hypercholesterolaemia: a meta-analysis.

Familial hypercholesterolaemia (FH) is a highly prevalent monogenic disorder characterized by elevated LDL cholesterol (LDL-C) levels and premature atherosclerotic cardiovascular disease. Sex disparities in diagnosis, lipid-lowering therapy, and achieved lipid levels have emerged worldwide, resulting in barriers to care in FH. A systematic review was performed to investigate sex-related disparities in treatment, response, and lipid target achievement in FH (PROSPERO, CRD42022353297). MEDLINE, Embase, The Cochrane library, PubMed, Scopus, PsycInfo, and grey literature databases were searched from inception to 26 April 2023. Records were eligible if they described sex differences in the treatment of adults with FH. Of 4432 publications reviewed, 133 met our eligibility criteria. In 16 interventional clinical trials (eight randomized and eight non-randomized; 1840 participants, 49.4% females), there were no differences between males and females in response to fixed doses of lipid-lowering therapy, suggesting that sex was not a determinant of response. Meta-analysis of 25 real-world observational studies (129 441 participants, 53.4% females) found that females were less likely to be on lipid-lowering therapy compared with males (odds ratio .74, 95% confidence interval .66-.85). Importantly, females were less likely to reach an LDL-C < 2.5 mmol/L (odds ratio .85, 95% confidence interval .74-.97). Similarly, treated LDL-C levels were higher in females. Despite this, male sex was associated with a two-fold greater relative risk of major adverse cardiovascular events including myocardial infarction, atherosclerotic cardiovascular disease, and cardiovascular mortality. Females with FH were less likely to be treated intensively and to reach guideline-recommended LDL-C targets. This sex bias represents a surmountable barrier to clinical care.

Sex differences in pelvic size and shape in the striped field mouse from Slovakia

Morphometric analysis and evaluation of 260 striped field mice (Apodemus agrarius) were carried out to identify sexual size dimorphism in pelvic bones regarding the age of individuals and the reproductive history of females. Pelvic size was found to differ between subadult and adult individuals of both sexes. A comparison using the Mann–Whitney U test between the right and left parts of the pelvis showed statistically non-significant differences between the pelvis dimensions. In the inter-sexual comparison of both ages (subadult, adult), statistically significant differences were found for only four traits in adults: length of the coxal bone (LP1), width of the ischiopubis (WP1), length of the obturator foramen (LSF) and width of the obturator foramen (WSF). The two indices (WSF/LSF and WP1/LP2) evaluated clearly reflected changes in the pelvic shape, which were most pronounced in adult mice. For the group of subadult males and females, the differences in measured traits and indices were not as pronounced. Several analyses, such as the Mann–Whitney U test, principal component analysis (PCA) as well as discriminant analysis (DFA), showed sex differences in pelvic morphology and shape, although the two sexes overlapped. Similarly, one-way ANCOVA showed that there was a significant difference between the sexes for the adjusted means. Analyses showed that for a given body mass, it appears that females tend to have larger pelvises. Thus, the sexual dimorphism of females was related to pelvic size and shape in A. agrarius. The breeding history showed differences in pelvic dimensions in following direction: the nulliparous < primigravid < primiparous direction.

Impact of antenatal exposure to a mixture of persistent organic pollutants on intellectual development

ObjectiveStrong experimental evidence exists that several endocrine disrupting chemicals (EDCs) have neurobehavioral toxicity. However, evidence of associations between prenatal exposure and child’s cognitive development is inconsistent. Moreover, toxicants are generally analyzed one by one without considering aggregate effects. We examined here the impact of a prenatal exposure to a mixture of persistent organic pollutants (POPs) on intellectual abilities in preschool children, and compared their effects to those described in the literature. MethodsSixty-two children were included in a longitudinal cohort. Four organochlorine pesticides, four polychlorinated biphenyls (PCBs) and seven perfluorinated compounds (PFCs) were measured in cord blood. Intellectual abilities were assessed at 6 years of age using the Wechsler Preschool and Primary Scale of Intelligence 4rd ed. (WPPSI-IV). We examined the associations between a mixture of POPs and cognitive performances using principal components approach (PCA) and weighted quantile sum (WQS) regression taking sex difference into account. ResultsNo negative correlation was found when analyses were performed on boys and girls together. In sex-stratified analyses, lower scores in full scale intelligence quotient (FSIQ) and fluid reasoning index (FRI) were observed in boys most exposed to a mixture of POPs. Increase of the WQS index was also associated with lower verbal comprehension index (VCI) scores in girls only. No other negative correlation was found using both WQS and PCA models. ConclusionOur study suggests deleterious associations between antenatal exposure to a mixture of POPs and sex-specific cognitive level, clarifying some trends described in the literature.

Hair pulling in a sample of Turkish university students: prevalence, clinical characteristics, predictors, and sex differences

Hair pulling in a sample of Turkish university students: prevalence, clinical characteristics, predictors, and sex differences

Sex differences in unmet needs between male and female older veterans

Aging Veterans face complex needs across multiple domains. However, the needs of older female Veterans and the degree to which unmet needs differ by sex are unknown. We analyzed responses to the HERO CARE survey from 7,955 Veterans aged 55 years and older (weighted N = 490,148), 93.9% males and 6.1% females. We evaluated needs and unmet needs across the following domains: activities of daily living (ADLs), instrumental ADLs (IADLs), health management, and social. We calculated weighted estimates and compared sex differences using age-adjusted prevalence ratios. On average, female Veterans were younger, more were Non-Hispanic Black and unmarried. Females and males reported a similar prevalence of problems across all domains. However, compared to males, female Veterans had a lesser prevalence of missed appointments due to transportation (aPR 0.49; 95% CI: 0.26–0.92), housework unmet needs (aPR: 0.44; 95% CI: 0.20–0.97), and medication management unmet needs (aPR: 0.33; 95% CI: 0.11–0.95) but a higher prevalence of healthcare communication unmet needs (aPR: 2.40; 95% CI: 1.13–5.05) and monitoring health conditions unmet needs (aPR: 2.13, 95% CI: 1.08–4.20). Female Veterans’ common experience of unmet needs in communicating with their healthcare teams could result in care that is less aligned with their preferences or needs. As the number of older female Veterans grows, these data and additional work to understand sex-specific unmet needs and ways to address them are essential to providing high-quality care for female Veterans.

Sex differences in unmet needs between male and female older veterans

Aging Veterans face complex needs across multiple domains. However, the needs of older female Veterans and the degree to which unmet needs differ by sex are unknown. We analyzed responses to the HERO CARE survey from 7,955 Veterans aged 55 years and older (weighted N = 490,148), 93.9% males and 6.1% females. We evaluated needs and unmet needs across the following domains: activities of daily living (ADLs), instrumental ADLs (IADLs), health management, and social. We calculated weighted estimates and compared sex differences using age-adjusted prevalence ratios. On average, female Veterans were younger, more were Non-Hispanic Black and unmarried. Females and males reported a similar prevalence of problems across all domains. However, compared to males, female Veterans had a lesser prevalence of missed appointments due to transportation (aPR 0.49; 95% CI: 0.26–0.92), housework unmet needs (aPR: 0.44; 95% CI: 0.20–0.97), and medication management unmet needs (aPR: 0.33; 95% CI: 0.11–0.95) but a higher prevalence of healthcare communication unmet needs (aPR: 2.40; 95% CI: 1.13–5.05) and monitoring health conditions unmet needs (aPR: 2.13, 95% CI: 1.08–4.20). Female Veterans’ common experience of unmet needs in communicating with their healthcare teams could result in care that is less aligned with their preferences or needs. As the number of older female Veterans grows, these data and additional work to understand sex-specific unmet needs and ways to address them are essential to providing high-quality care for female Veterans.

Normal values of scapular muscle activity ratio during arm elevation and the relationship to muscle strength and sex difference.

The normal value of the scapular muscle activity ratio during arm elevation is not clear. To obtain normal values of the scapular muscle activity ratio during arm elevation in healthy individuals. This cross-sectional study enrolled 47 healthy people. The participants performed shoulder flexion and lowered task with 90-degree movements every 2 seconds. Muscle activities of scapular muscles were measured. For normalization, the maximum isometric contraction of the shoulder flexion was measured at 90∘ (reference contraction). The integrated electromyographic value (IEMG) obtained during the task was normalized by IEMG during the reference contraction and the relative IEMG value was calculated. Then, the scapular muscle activity ratio was computed. The relationship between muscle strength and other factors was also investigated. The median values for upper trapezius/serratus anterior and upper trapezius/lower trapezius were often approximately 1, and that for upper trapezius/middle trapezius was often between 1 and 2. The shoulder flexion isometric strength and scapular muscle activity ratio showed significant negative correlations in multiple phases. Normal values for upper trapezius/serratus anterior and upper trapezius/lower trapezius during arm elevation and lowering were generally 1. Low muscle strength may contribute to an abnormal scapular muscle activity balance.

Age and sex differences in the effects of short- and long-term exposure to air pollution on endothelial dysfunction.

The effects of air pollution on endothelial function remain unclear across populations. We aimed to use brachial artery flow-mediated dilatation (FMD) to identify demographic differences in the effects of air pollution exposure on endothelial dysfunction. We measured FMD in 850 participants from October 2016 to January 2020. Location-specific concentrations of fine particulate matter < 2.5μm aerodynamic diameter (PM2.5), inhalable particulate matter < 10μm aerodynamic diameter (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) measured by fixed ambient air monitoring stations were collected for short- and long-term exposure assessment. Multiple linear regression models and restricted cubic splines were used to assess the associations before and after stratification by age and sex. This study eventually included 828 participants [551 (66.5%) younger than 65 years and 553 (66.8%) men]. Each 10µg/m3 increase in 7-day exposure to PM2.5 and PM10 was significantly linearly associated with a 0.07% (β = -0.07, 95% CI: -0.13 to -0.004) and 0.05% (β = -0.05, 95% CI: -0.10 to -0.004) decrease in FMD in the fully adjusted model. After full adjustment, long-term exposure to all air pollutants was significantly associated with impaired FMD. Each 10µg/m3 increase in long-term exposure to PM2.5 and PM10 was significantly associated with a -0.18% (95% CI: -0.34 to -0.03) and - 0.23% (95% CI: -0.40 to -0.06) change in FMD, respectively. After stratification, the associations of lower FMD with long-term exposure to PM2.5, PM10, SO2, NO2, and CO significantly persisted in men and participants younger than 65 years instead of women or older participants. For short-term exposure, we observed differences consistent with long-term exposure and a stronger effect of 7-day exposure to SO2 in men due to a significant interaction effect. Short- and long-term exposure to different air pollutants are strongly associated with decreased endothelial function, and susceptibility to air pollution varies significantly with age and sex.

High Prevalence and Broad Distribution of Trichomonas gypaetinii in Bald Eagles (Haliaceetus leucocephalus) in the USA.

Trichomonas gypaetinii was detected in 117 (88%) of 133 Bald Eagles (Haliaceetus leucocephalus) and in 0 of 7 Golden Eagles (Aquila chrysaetos) in the USA, with no sex or age prevalence difference. All eagles lacked associated lesions. This study indicated that T. gypaetinii is common and widespread in Bald Eagles, but rarely associated with disease.

Assessment of Sexual Dimorphism Through Lateral Cephalogram in Children Aged 10-12 Years

Assessment of Sexual Dimorphism Through Lateral Cephalogram in Children Aged 10-12 Years

Lie to me to lay with me: Females deceive males via terminal investment.

Historically, males have frequently been portrayed as the manipulative and deceptive gender, while females are often seen as adopting a coy and passive role. In this context, it is proposed that males use a terminal investment strategy, misleading females about their true poor condition, while females passively opt to mate with these deceptive males. However, we hypothesize that females in suboptimal condition may also engage in a terminal investment strategy by mimicking or enhancing their attractiveness to match that of females in better conditions. We studied this hypothesis in Tenebrio molitor, by subjecting females to three varying doses of lipopolysaccharides of Escherichia coli (LPS; 0.25, 0.5, or 1 mg ml-1), or three doses of the pro-oxidant Paraquat (PQ; 20, 40 or 80 mM), and subsequently assessing their survival and attractiveness to males. The LPS treatments and 20 mM of PQ had no significant effect on the survival or attractiveness of the females. However, females treated with 40 or 80 mM PQ survived fewer days compared to the control group. Those injected with 40 mM were more attractive than their control counterparts, while those treated with 80 mM were less attractive. Since the identical doses of LPS, which induce terminal investment in males, had no effect on females, we suggest sexual dimorphism in terminal investment. Furthermore, similar to males, if the stressor reaches a sufficiently high level, the signal becomes honest. These findings highlight how the quantity of stressors influences support for the terminal investment strategy in both males and females. Notably, this study challenges prevailing notions regarding gender roles in sexual selection, indicating that females, not just males, conceal their poor condition to attract mating partners.

Two new genera of coastal Talitridae (Amphipoda: Senticaudata) from Chile, with the first record of Platorchestia Bousfield, 1982 in the southeastern Pacific coast

Using samples of talitrid amphipods collected on the coast of Chile, we describe two new monotypic genera characterized by particular types of sexual dimorphism, and we report the first record of the genus Platorchestia Bousfield, 1982 in the southeastern Pacific coast. In the subfamily Platorchestiinae, the genus Atacamorchestia gen. nov. and its new species Atacamorchestia atacamensis sp. nov. was collected in marine rocky coasts, in several localities in northern Chile. This new taxon is characterized principally by presence of T setae in male appendages, a feature shared with the genus Vallorchestia from Australia, but with a different distribution of these structures. The first specimens of Platorchestia in the Southeastern Pacific were obtained in Antofagasta, northern Chile, however they were identified only to genus level because a more in-depth taxonomic analysis will be necessary to determine their status. Finally, in the subfamily Talitrinae, Lafkenorchestia gen. nov. and its new species Lafkenorchestia oyarzuni sp. nov. were found on rocky marine shores and in estuaries in southern Chile, between La Araucania and Los Lagos regions. This new taxon is characterized by distinct modifications in basis and merus of male pereopod 7, showing some morphological similarities with the New Zealand genera Subantarctorchestia and Pictonorchestia. For each species, descriptions and illustrations are presented.

Changes in the wing shape and size in fruit flies exposed to micro and nanoplastics

Geometric morphometrics analysis (GMA) is a well-known technique to identify minute changes in Drosophila wings. This study aimed to determine potential changes in Drosophila wings shape and size after exposure to polystyrene nanoplastics (NPs) (50 nm) and microplastics (MPs) (1 μm). Flies were exposed from eggs to pupal eclosion and analyzed using GMA. Results revealed a difference in shape and size between male and female wings, as expected, due to sexual dimorphism. Therefore, wings were analyzed by sex. Wings of MPs and NPs treated females were elongated compared to controls and had a constriction of the wing joint. Additionally, MPs treated female flies had the most dissimilar shape compared to controls. In male flies, NPs flies had smaller wings compared to MPs and control flies. Compared to control, NPs wings of males were shrunken at the joint and in the entire proximal region of the wing. However, male MPs wings had a narrower anal region and were slightly elongated. These results reveal that wing shape and size can change in a different way based on the sex of the flies and size of plastic particles that larvae interacted with. All the changes in the wings occurred only within the normally allowed wing variation and treatment with NPs/MPs did not cause development of the aberrant phenotypes. Results can pave the way for further understanding of how MPs and NPs can alter phenotypes of flies.

Phylogenetic and transcriptomic study of aldo-keto reductases in Haemonchus contortus and their inducibility by flubendazole

Aldo-keto reductases (AKRs), a superfamily of NADP(H)-dependent oxidoreductases, catalyze the oxidoreduction of a wide variety of eobiotic and xenobiotic aldehydes and ketones. In mammals, AKRs play essential roles in hormone and xenobiotic metabolism, oxidative stress, and drug resistance, but little is known about these enzymes in the parasitic nematode Haemonchus contortus. In the present study, 22 AKR genes existing in the H. contortus genome were investigated and a phylogenetic analysis with comparison to AKRs in Caenorhabditis elegans, sheep and humans was conducted. The constitutive transcription levels of all AKRs were measured in eggs, larvae, and adults of H. contortus, and their expression was compared in a drug-sensitive strain (ISE) and a benzimidazole-resistant strain (IRE) previously derived from the sensitive strain by imposing benzimidazole selection pressure. In addition, the inducibility of AKRs by exposure of H. contortus adults to benzimidazole anthelmintic flubendazole in vitro was tested. Phylogenetic analysis demonstrated that the majority of AKR genes in H. contortus lack orthologues in the sheep genome, which is a favorable finding for considering AKRs as potential drug targets. Large differences in the expression levels of individual AKRs were observed, with AKR1, AKR3, AKR8, and AKR10 being the most highly expressed at most developmental stages. Significant changes in the expression of AKRs during the life cycle and pronounced sex differences were found. Comparing the IRE and ISE strains, three AKRs were upregulated, and seven AKRs were downregulated in adults. In addition, the expression of three AKRs was induced by flubendazole exposure in adults of the ISE strain. Based on these results, AKR1, AKR2, AKR3, AKR5, AKR10 and AKR19 in particular merit further investigation and functional characterization with respect to their potential involvement in drug biotransformation and anthelmintic resistance in H. contortus.

Sex-specific alterations in visual properties induced by single prolonged stress model

Patients with post-traumatic stress disorder (PTSD) exhibit sex differences in symptomology, with women more likely to report higher rates of intrusive and avoidance symptoms than men, underscoring the need for sex-informed approaches to research and treatment. Our study delved into the sex-specific aspects of stress-induced visual impairments using the single prolonged stress (SPS) model, a partially validated rodent model for PTSD. Male SPS mice exhibit heightened optimal spatial frequency (SF) of primary visual cortex (V1) neurons, while female counterparts exhibit decreased optimal temporal frequency (TF) of V1 neurons. This phenomenon persisted until the 29th day after SPS modeling, and it may be the physiological basis for the observed increase in visual acuity in male SPS mice in visual water task. Furthermore, our study found that corticotropin-releasing factor receptor 1 regulated optimal TF and optimal SF of V1 in mice, but did not exhibit sex differences. These findings indicated that severe stress induces sex-specific effects on visual function.

Subregion-specific transcriptomic profiling of rat brain reveals sex-distinct gene expression impacted by adolescent stress

Stress during adolescence clearly impacts brain development and function. Sex differences in adolescent stress-induced or exacerbated emotional and metabolic vulnerabilities could be due to sex-distinct gene expression in hypothalamic, limbic, and prefrontal brain regions. However, adolescent stress-induced whole-genome expression changes in key subregions of these brain regions were unclear. In this study, female and male adolescent Sprague Dawley rats received one-hour restraint stress daily from postnatal day (PD) 32 to PD44. Corticosterone levels, body weights, food intake, body composition, and circulating adiposity and sex hormones were measured. On PD44, brain and blood samples were collected. Using RNA-sequencing, sex-specific differences in stress-induced differentially expressed (DE) genes were identified in subregions of the hypothalamus, limbic system, and prefrontal cortex. Canonical pathways reflected well-known sex-distinct maladies and diseases, substantiating the therapeutic potential of the DE genes found in the current study. Thus, we proposed specific sex distinct, adolescent stress-induced transcriptional changes found in the current study as examples of the molecular bases for sex differences witnessed in stress induced or exacerbated emotional and metabolic disorders. Future behavioral studies and single-cell studies are warranted to test the implications of the DE genes identified in this study in sex-distinct stress-induced susceptibilities.