Biology of Sex Differences最新文献

{"title":"Sex- and species-specific contribution of CD99 to T cell costimulation during multiple sclerosis.","authors":"Ingo Winschel, Anne Willing, Jan Broder Engler, Mark Walkenhorst, Nina Meurs, Lars Binkle-Ladisch, Marcel S Woo, Lena Kristina Pfeffer, Jana K Sonner, Uwe Borgmeyer, Sven Hendrik Hagen, Benjamin Grünhagel, Janna M Claussen, Marcus Altfeld, Manuel A Friese","doi":"10.1186/s13293-024-00618-y","DOIUrl":"10.1186/s13293-024-00618-y","url":null,"abstract":"<p><strong>Background: </strong>Differences in immune responses between women and men are leading to a strong sex bias in the incidence of autoimmune diseases that predominantly affect women, such as multiple sclerosis (MS). MS manifests in more than twice as many women, making sex one of the most important risk factor. However, it is incompletely understood which genes contribute to sex differences in autoimmune incidence. To address that, we conducted a gene expression analysis in female and male human spleen and identified the transmembrane protein CD99 as one of the most significantly differentially expressed genes with marked increase in men. CD99 has been reported to participate in immune cell transmigration and T cell regulation, but sex-specific implications have not been comprehensively investigated.</p><p><strong>Methods: </strong>In this study, we conducted a gene expression analysis in female and male human spleen using the Genotype-Tissue Expression (GTEx) project dataset to identify differentially expressed genes between women and men. After successful validation on protein level of human immune cell subsets, we assessed hormonal regulation of CD99 as well as its implication on T cell regulation in primary human T cells and Jurkat T cells. In addition, we performed in vivo assays in wildtype mice and in Cd99-deficient mice to further analyze functional consequences of differential CD99 expression.</p><p><strong>Results: </strong>Here, we found higher CD99 gene expression in male human spleens compared to females and confirmed this expression difference on protein level on the surface of T cells and pDCs. Androgens are likely dispensable as the cause shown by in vitro assays and ex vivo analysis of trans men samples. In cerebrospinal fluid, CD99 was higher on T cells compared to blood. Of note, male MS patients had lower CD99 levels on CD4⁺ T cells in the CSF, unlike controls. By contrast, both sexes had similar CD99 expression in mice and Cd99-deficient mice showed equal susceptibility to experimental autoimmune encephalomyelitis compared to wildtypes. Functionally, CD99 increased upon human T cell activation and inhibited T cell proliferation after blockade. Accordingly, CD99-deficient Jurkat T cells showed decreased cell proliferation and cluster formation, rescued by CD99 reintroduction.</p><p><strong>Conclusions: </strong>Our results demonstrate that CD99 is sex-specifically regulated in healthy individuals and MS patients and that it is involved in T cell costimulation in humans but not in mice. CD99 could potentially contribute to MS incidence and susceptibility in a sex-specific manner.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"41"},"PeriodicalIF":4.9,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097467/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140943903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early adversity causes sex-specific deficits in perforant pathway connectivity and contextual memory in adolescent mice.","authors":"Rafiad Islam, Jordon D White, Tanzil M Arefin, Sameet Mehta, Xinran Liu, Baruh Polis, Lauryn Giuliano, Sahabuddin Ahmed, Christian Bowers, Jiangyang Zhang, Arie Kaffman","doi":"10.1186/s13293-024-00616-0","DOIUrl":"10.1186/s13293-024-00616-0","url":null,"abstract":"<p><strong>Background: </strong>Early life adversity impairs hippocampal development and function across diverse species. While initial evidence indicated potential variations between males and females, further research is required to validate these observations and better understand the underlying mechanisms contributing to these sex differences. Furthermore, most of the preclinical work in rodents was performed in adult males, with only few studies examining sex differences during adolescence when such differences appear more pronounced. To address these concerns, we investigated the impact of limited bedding (LB), a mouse model of early adversity, on hippocampal development in prepubescent and adolescent male and female mice.</p><p><strong>Methods: </strong>RNA sequencing, confocal microscopy, and electron microscopy were used to evaluate the impact of LB and sex on hippocampal development in prepubescent postnatal day 17 (P17) mice. Additional studies were conducted on adolescent mice aged P29-36, which included contextual fear conditioning, retrograde tracing, and ex vivo diffusion magnetic resonance imaging (dMRI).</p><p><strong>Results: </strong>More severe deficits in axonal innervation and myelination were found in the perforant pathway of prepubescent and adolescent LB males compared to LB female littermates. These sex differences were due to a failure of reelin-positive neurons located in the lateral entorhinal cortex (LEC) to innervate the dorsal hippocampus via the perforant pathway in males, but not LB females, and were strongly correlated with deficits in contextual fear conditioning.</p><p><strong>Conclusions: </strong>LB impairs the capacity of reelin-positive cells located in the LEC to project and innervate the dorsal hippocampus in LB males but not female LB littermates. Given the critical role that these projections play in supporting normal hippocampal function, a failure to establish proper connectivity between the LEC and the dorsal hippocampus provides a compelling and novel mechanism to explain the more severe deficits in myelination and contextual freezing found in adolescent LB males.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"39"},"PeriodicalIF":4.9,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11075329/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140875740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences of post-Covid patients undergoing outpatient pulmonary rehabilitation","authors":"Alexander Kautzky, Stephan Nopp, Dietlinde Gattinger, Milos Petrovic, Martin Antlinger, Dustin Schomacker, Alexandra Kautzky-Willer, Ralf Harun Zwick","doi":"10.1186/s13293-024-00609-z","DOIUrl":"https://doi.org/10.1186/s13293-024-00609-z","url":null,"abstract":"Following years of pandemic severe acute respiratory syndrome coronavirus 2 infections labelled Covid-19, long lasting impairment summarized as post-Covid syndrome (PCS) challenges worldwide healthcare. Patients benefit from rehabilitation programs, but sex specific aspects of improvement remain little understood. The aim of the study was to assess whether women and men differ in response to outpatient pulmonary rehabilitation for PCS. 263 (54.4% female) patients partaking in outpatient pulmonary rehabilitation (OPR) due to PCS between March 2020 and July 2022 were included in a prospective observational cohort study. Outcomes were assessed at baseline and before discharge from OPR and included six-minute walking distance (6MWD), 1-second forced expiratory volume (FEV1), diffusion capacity for carbon monoxide, maximal inspiratory pressure (MIP), dyspnea (medical research council scale), and post-Covid functional status scale (PCFS). Sexspecific changes in outcomes following OPR were assessed by linear mixed model and presented as mean differences (MD) with 95% confidence intervals. Linear regression was applied to test whether 6MWD correlates with PCFS and the minimal clinically important difference (MCID) in 6MWD regarding an improvement of at least one point in PCFS was computed with logistic regression. Significant improvement throughout OPR was observed for all outcomes (all p &lt; 0.0001). Despite less severe Covid-19 infections, PCFS scores remained higher in females after OPR (p = 0.004) and only 19.4% of women compared to 38.5% of men achieved remission of functional impairment. At baseline as well as after OPR, females showed higher symptom load compared to men in dyspnea (p = 0.0027) and scored lower in FEV1 (p = 0.009) and MIP (p = 0.0006) assessment. Performance in 6MWD was comparable between men and women. An increase of 35 m in 6MWD was computed as minimal clinically important difference to improve functional impairment. Both subjective symptoms such as fatigue and dyspnea and objective impairment in performance in pulmonary function were more frequently observed among women. Despite improvement throughout OPR in both women and men, the sex-gap in symptom load could not be closed as women less often achieved remission from functional impairment due to PCS. Intensified treatment of these symptoms should be considered in women undergoing rehabilitation for PCS. While female sex is protective during the acute infection of Covid-19, women are at increased risk of developing post-Covid syndrome (PCS) even after only mild Covid-19 infections. Severity and frequency of symptoms such as fatigue and shortness of breath are known to be higher in women compared to men. Many different rehabilitation protocols are used for PCS, but a knowledge gap regarding sex related differences in rehabilitation success remains. Both female and male patients with PCS undergoing outpatient pulmonary rehabilitation improved in the maximum walking distance achieved","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"19 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Treating sex and gender differences as a continuous variable can improve precision cancer treatments","authors":"Wei Yang, Joshua B. Rubin","doi":"10.1186/s13293-024-00607-1","DOIUrl":"https://doi.org/10.1186/s13293-024-00607-1","url":null,"abstract":"The significant sex and gender differences that exist in cancer mechanisms, incidence, and survival, have yet to impact clinical practice. One barrier to translation is that cancer phenotypes cannot be segregated into distinct male versus female categories. Instead, within this convenient but contrived dichotomy, male and female cancer phenotypes are highly overlapping and vary between female- and male- skewed extremes. Thus, sex and gender-specific treatments are unrealistic, and our translational goal should be adaptation of treatment to the variable effects of sex and gender on targetable pathways. To overcome this obstacle, we profiled the similarities in 8370 transcriptomes of 26 different adult and 4 different pediatric cancer types. We calculated the posterior probabilities of predicting patient sex and gender based on the observed sexes of similar samples in this map of transcriptome similarity. Transcriptomic index (TI) values were derived from posterior probabilities and allowed us to identify poles with local enrichments for male or female transcriptomes. TI supported deconvolution of transcriptomes into measures of patient-specific activity in sex and gender-biased, targetable pathways. It identified sex and gender-skewed extremes in mechanistic phenotypes like cell cycle signaling and immunity, and precisely positioned each patient’s whole transcriptome on an axis of continuously varying sex and gender phenotypes. Cancer type, patient sex and gender, and TI value provides a novel and patient- specific mechanistic identifier that can be used for realistic sex and gender-adaptations of precision cancer treatment planning. Some efforts to improve cancer therapy involve the idea of personalizing treatments to who a patient is and how their cancer operates. Personalizing treatment can involve straighforward features like a patient’s age, family cancer history, personal disease and surgical histories, as well as more complex features like analysis of their specific cancer’s mechanisms of growth and spread throughout the body. One glaring omission in common personalization schemes is the sex and gender of the patient. While patient sex and gender is known to substantially affect cancer rates and response to treatment, we do not yet use this information in treatment planning. There are multiple reasons for this but among them is that we tend to think about sex and gender as an either/or categorization. You are either a male/man or a female/woman. This is not accurate as there are many variables that contribute to who an individual is as a male/man or female/woman. This variability is a challenge to incorporating these features into personalized treatment planning. Here, we have developed a method to address this challenge. It is our great hope that this will enable the use of this critically important element of personalization in cancer treatment planning and improve survival rates for all patients. ","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"57 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-based differences in growth-related IGF1 signaling in response to PAPP-A2 deficiency: comparative effects of rhGH, rhIGF1 and rhPAPP-A2 treatments","authors":"María del Mar Fernández-Arjona, Juan Antonio Navarro, Antonio Jesús López-Gambero, Marialuisa de Ceglia, Miguel Rodríguez, Leticia Rubio, Fernando Rodríguez de Fonseca, Vicente Barrios, Julie A. Chowen, Jesús Argente, Patricia Rivera, Juan Suárez","doi":"10.1186/s13293-024-00603-5","DOIUrl":"https://doi.org/10.1186/s13293-024-00603-5","url":null,"abstract":"Children with pregnancy-associated plasma protein-A2 (PAPP-A2) mutations resulting in low levels of bioactive insulin-like growth factor-1 (IGF1) and progressive postnatal growth retardation have improved growth velocity and height following recombinant human (rh)IGF1 treatment. The present study aimed to evaluate whether Pappa2 deficiency and pharmacological manipulation of GH/IGF1 system are associated with sex-specific differences in growth-related signaling pathways. Plasma, hypothalamus, pituitary gland and liver of Pappa2ko/ko mice of both sexes, showing reduced skeletal growth, and liver of these mice treated with rhGH, rhIGF1 and rhPAPP-A2 from postnatal day (PND) 5 to PND35 were analyzed. Reduced body and femur length of Pappa2ko/ko mice was associated with increases in: (1) components of IGF1 ternary complexes (IGF1, IGFBP5/Igfbp5, Igfbp3, Igfals) in plasma, hypothalamus and/or liver; and (2) key signaling regulators (phosphorylated PI3K, AKT, mTOR, GSK3β, ERK1/2 and AMPKα) in hypothalamus, pituitary gland and/or liver, with Pappa2ko/ko females having a more prominent effect. Compared to rhGH and rhIGF1, rhPAPP-A2 specifically induced: (1) increased body and femur length, and reduced plasma total IGF1 and IGFBP5 concentrations in Pappa2ko/ko females; and (2) increased Igf1 and Igf1r levels and decreased Ghr, Igfbp3 and Igfals levels in the liver of Pappa2ko/ko females. These changes were accompanied by lower phospho-STAT5, phospho-AKT and phospho-ERK2 levels and higher phospho-AMPK levels in the liver of Pappa2ko/ko females. Sex-specific differences in IGF1 system and signaling pathways are associated with Pappa2 deficiency, pointing to rhPAPP-A2 as a promising drug to alleviate postnatal growth retardation underlying low IGF1 bioavailability in a female-specific manner. Understanding the physiological role of pregnancy-associated plasma protein-A2 (PAPP-A2), a proteinase involved in the insulin-like growth factor-1 (IGF1) availability to regulate growth, could provide insight into new treatments for patients with short stature and skeletal abnormalities. Although progressive postnatal growth retardation in patients with PAPP-A2 mutations can differ between males and females, we do not know the underlying differences in IGF1 system and signaling, and their response to treatment that contribute to growth improvement. The present study examines whether Pappa2 deficiency and pharmacological administration of rhGH, rhIGF1 and rhPAPP-A2 are associated with sex-specific differences in IGF1 ternary complexes and IGF1 signaling pathways. Reduced body and femur length of Pappa2-deficient mice was associated with sex- and tissue-specific alteration of IGF ternary/binary complexes and IGF1 signaling pathways. rhPAPP-A2 treatment induced female-specific increase in body and femur length and reduction in IGF ternary/binary complexes through STAT5-AKT-ERK2-AMPK signaling pathways in liver. The involvement of PAPP-A2 in sex-based growth physiology sup","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"6 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences and sex-specific regulation of motivated behavior by Melanin-concentrating hormone: a short review","authors":"Isabel R. K. Kuebler, Mauricio Suárez, Ken T. Wakabayashi","doi":"10.1186/s13293-024-00608-0","DOIUrl":"https://doi.org/10.1186/s13293-024-00608-0","url":null,"abstract":"Recent preclinical research exploring how neuropeptide transmitter systems regulate motivated behavior reveal the increasing importance of sex as a critical biological variable. Neuropeptide systems and their central circuits both contribute to sex differences in a range of motivated behaviors and regulate sex-specific behaviors. In this short review, we explore the current research of how sex as a biological variable influences several distinct motivated behaviors that are modulated by the melanin-concentrating hormone (MCH) neuropeptide system. First, we review how MCH regulates feeding behavior within the context of energy homeostasis differently between male and female rodents. Then, we focus on MCH’s role in lactation as a sex-specific process within the context of energy homeostasis. Next, we discuss the sex-specific effects of MCH on maternal behavior. Finally, we summarize the role of MCH in drug-motivated behaviors. While these topics are traditionally investigated from different scientific perspectives, in this short review we discuss how these behaviors share commonalities within the larger context of motivated behaviors, and that sex differences discovered in one area of research may impact our understanding in another. Overall, our review highlights the need for further research into how sex differences in energy regulation associated with reproduction and parental care contribute to regulating motivated behaviors.","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"32 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats","authors":"Ryan T. McCallum, Rachel-Karson Thériault, Joshua D. Manduca, Isaac S. B. Russell, Angel M. Culmer, Janan Shoja Doost, Tami A. Martino, Melissa L. Perreault","doi":"10.1186/s13293-024-00605-3","DOIUrl":"https://doi.org/10.1186/s13293-024-00605-3","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Biol Sex Differ 15, 16 (2024)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;https://doi.org/10.1186/s13293-024-00589-0&lt;/p&gt;&lt;p&gt; Following publication of the original article [1], the authors reported an error in the methodology for calculating the discrimination ratio in the novel object recognition and object location tests.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Incorrect&lt;/b&gt;: The discrimination ratio was calculated as the time of exploration of relocated object/total object exploration time*100.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Correct&lt;/b&gt;: For the novel object recognition test the discrimination ratio was calculated as the time exploring the novel object – the time exploring the familiar object/total exploration time.&lt;/p&gt;&lt;p&gt;For the object location test the discrimination ratio was calculated as the time exploring the novel location – the time exploring the familiar location/total exploration time.&lt;/p&gt;&lt;p&gt; The authors also report an error in sampling for original Figs. 4 and 5. Therefore, all of the original microglia data in the results and figures have been removed and Fig. 6 renumbered as Fig. 4. The associated immunohistochemistry methodologies were removed, and any associated discussion of the microglia findings deleted. References were renumbered and the Abstract and Highlights also revised to remove the microglia findings.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;McCallum RT, Thériault RK, Manduca JD, et al. Nrf2 activation rescues stress-induced depression-like behaviour and inflammatory responses in male but not female rats. Biol Sex Differ. 2024;15:16. https://doi.org/10.1186/s13293-024-00589-0.&lt;/p&gt;&lt;p&gt;Article CAS PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Department of Biomedical Sciences, University of Guelph, 50 Stone Rd. E, Guelph, ON, N1G 2W1, Canada&lt;/p&gt;&lt;p&gt;Ryan T. McCallum, Rachel-Karson Thériault, Joshua D. Manduca, Isaac S. B. Russell, Angel M. Culmer, Janan Shoja Doost, Tami A. Martino &amp; Melissa L. Perreault&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Ryan T. McCallum&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Rachel-Karson Thériault&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Joshua D. Manduca&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Isaac S. B. Russell&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Angel M. Culmer&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"207 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140593821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Training in the implementation of sex and gender research policies: an evaluation of publicly available online courses","authors":"Annika Gompers, Madeline T. Olivier, Donna L. Maney","doi":"10.1186/s13293-024-00610-6","DOIUrl":"https://doi.org/10.1186/s13293-024-00610-6","url":null,"abstract":"Recently implemented research policies requiring the inclusion of females and males have created an urgent need for effective training in how to account for sex, and in some cases gender, in biomedical studies. Here, we evaluated three sets of publicly available online training materials on this topic: (1) Integrating Sex & Gender in Health Research from the Canadian Institutes of Health Research (CIHR); (2) Sex as a Biological Variable: A Primer from the United States National Institutes of Health (NIH); and (3) The Sex and Gender Dimension in Biomedical Research, developed as part of “Leading Innovative measures to reach gender Balance in Research Activities” (LIBRA) from the European Commission. We reviewed each course with respect to their coverage of (1) What is required by the policy; (2) Rationale for the policy; (3) Handling of the concepts “sex” and “gender;” (4) Research design and analysis; and (5) Interpreting and reporting data. All three courses discussed the importance of including males and females to better generalize results, discover potential sex differences, and tailor treatments to men and women. The entangled nature of sex and gender, operationalization of sex, and potential downsides of focusing on sex more than other sources of variation were minimally discussed. Notably, all three courses explicitly endorsed invalid analytical approaches that produce bias toward false positive discoveries of difference. Our analysis suggests a need for revised or new training materials that incorporate four major topics: precise operationalization of sex, potential risks of over-emphasis on sex as a category, recognition of gender and sex as complex and entangled, and rigorous study design and data analysis. Recently implemented research policies requiring the inclusion of females and males have created an urgent need for effective training in how to account for sex, and in some cases gender, in biomedical studies. We evaluated three publicly available online trainings on this topic: (1) Integrating Sex & Gender in Health Research from the Canadian Institutes of Health Research; (2) Sex as a Biological Variable: A Primer from the United States National Institutes of Health; and (3) The Sex and Gender Dimension in Biomedical Research, developed as part of “Leading Innovative Measures to Reach Gender Balance in Research Activities (LIBRA)” from the European Commission. We reviewed each course with respect to their coverage of (1) What is required by the policy; (2) Rationale for the policy; (3) Handling of the concepts “sex” and “gender;” (4) Research design and analysis; and (5) Interpreting and reporting data. All three discussed the importance of including males and females to better generalize results, discover potential sex differences, and tailor treatments to men and women. The interconnectedness of sex and gender, how to operationalize sex, and potential downsides of focusing on sex more than other sources of variation were minimal","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"102 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TrkB-mediated neuroprotection in female hippocampal neurons is autonomous, estrogen receptor alpha-dependent, and eliminated by testosterone: a proposed model for sex differences in neonatal hippocampal neuronal injury","authors":"Vishal Chanana, Dila Zafer, Douglas B Kintner, Jayadevi H Chandrashekhar, Jens Eickhoff, Peter A Ferrazzano, Jon E Levine, Pelin Cengiz","doi":"10.1186/s13293-024-00596-1","DOIUrl":"https://doi.org/10.1186/s13293-024-00596-1","url":null,"abstract":" Following in vitro ischemia, the nerve growth factor receptor TrkB is activated in the presence of the TrkB agonist 7,8-DHF only in female and not in male cultured hippocampal neurons, leading to increased neuronal survival. Expression of ERα is increased following in vitro ischemia in female but not male hippocampal neurons. The female hippocampal neuronal specific responses to in vitro ischemia are blocked by pre-treatment with testosterone. The data support a model for a female-specific a neuroprotective pathway in hippocampal neurons. The pathway is activated by a TrkB agonist, dependent on ERα and blocked by testosterone. Neonatal hypoxia ischemia (HI) related brain injury is one of the major causes of learning disabilities and memory deficits in children. In both human and animal studies, female neonate brains are less susceptible to HI than male brains. Phosphorylation of the nerve growth factor receptor TrkB has been shown to provide sex-specific neuroprotection following in vivo HI in female mice in an estrogen receptor alpha (ERα)-dependent manner. However, the molecular and cellular mechanisms conferring sex-specific neonatal neuroprotection remain incompletely understood. Here, we test whether female neonatal hippocampal neurons express autonomous neuroprotective properties and assess the ability of testosterone (T) to alter this phenotype. We cultured sexed hippocampal neurons from ERα+/+ and ERα−/− mice and subjected them to 4 h oxygen glucose deprivation and 24 h reoxygenation (4-OGD/24-REOX). Sexed hippocampal neurons were treated either with vehicle control (VC) or the TrkB agonist 7,8-dihydroxyflavone (7,8-DHF) following in vitro ischemia. End points at 24 h REOX were TrkB phosphorylation (p-TrkB) and neuronal survival assessed by immunohistochemistry. In addition, in vitro ischemia-mediated ERα gene expression in hippocampal neurons were investigated following testosterone (T) pre-treatment and TrkB antagonist therapy via q-RTPCR. Multifactorial analysis of variance was conducted to test for significant differences between experimental conditions. Under normoxic conditions, administration of 3 µM 7,8-DHF resulted an ERα-dependent increase in p-TrkB immunoexpression that was higher in female, as compared to male neurons. Following 4-OGD/24-REOX, p-TrkB expression increased 20% in both male and female ERα+/+ neurons. However, with 3 µM 7,8-DHF treatment p-TrkB expression increased further in female neurons by 2.81 ± 0.79-fold and was ERα dependent. 4-OGD/24-REOX resulted in a 56% increase in cell death, but only female cells were rescued with 3 µM 7,8-DHF, again in an ERα dependent manner. Following 4-OGD/3-REOX, ERα mRNA increased ~ 3 fold in female neurons. This increase was blocked with either the TrkB antagonist ANA-12 or pre-treatment with T. Pre-treatment with T also blocked the 7,8-DHF- dependent sex-specific neuronal survival in female neurons following 4-OGD/24-REOX. OGD/REOX results in sex-dependent TrkB phosphorylatio","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"2 1","pages":""},"PeriodicalIF":7.9,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140594038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sexual differences in neuronal and synaptic properties across subregions of the mouse insular cortex.","authors":"Daniela Iezzi, Alba Cáceres-Rodríguez, Benjamin Strauss, Pascale Chavis, Olivier J Manzoni","doi":"10.1186/s13293-024-00593-4","DOIUrl":"10.1186/s13293-024-00593-4","url":null,"abstract":"<p><strong>Background: </strong>The insular cortex (IC) plays a pivotal role in processing interoceptive and emotional information, offering insights into sex differences in behavior and cognition. The IC comprises two distinct subregions: the anterior insular cortex (aIC), that processes emotional and social signals, and the posterior insular cortex (pIC), specialized in interoception and perception of pain. Pyramidal projection neurons within the IC integrate multimodal sensory inputs, influencing behavior and cognition. Despite previous research focusing on neuronal connectivity and transcriptomics, there has been a gap in understanding pyramidal neurons characteristics across subregions and between sexes.</p><p><strong>Methods: </strong>Adult male and female C57Bl/6J mice were sacrificed and tissue containing the IC was collected for ex vivo slice electrophysiology recordings that examined baseline sex differences in synaptic plasticity and transmission within aIC and pIC subregions.</p><p><strong>Results: </strong>Clear differences emerged between aIC and pIC neurons in both males and females: aIC neurons exhibited distinctive features such as larger size, increased hyperpolarization, and a higher rheobase compared to their pIC counterparts. Furthermore, we observed variations in neuronal excitability linked to sex, with male pIC neurons displaying a greater level of excitability than their female counterparts. We also identified region-specific differences in excitatory and inhibitory synaptic activity and the balance between excitation and inhibition in both male and female mice. Adult females demonstrated greater synaptic strength and maximum response in the aIC compared to the pIC. Lastly, synaptic long-term potentiation occurred in both subregions in males but was specific to the aIC in females.</p><p><strong>Conclusions: </strong>We conclude that there are sex differences in synaptic plasticity and excitatory transmission in IC subregions, and that distinct properties of IC pyramidal neurons between sexes could contribute to differences in behavior and cognition between males and females.</p>","PeriodicalId":8890,"journal":{"name":"Biology of Sex Differences","volume":"15 1","pages":"29"},"PeriodicalIF":7.9,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10983634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140334613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}