SRHR Aspiration Research Cluster Publications

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Prevalence and course of unwanted, intrusive thoughts of infant-related harm
(Journal of Clinical Psychiatry, 2024) Collardeau, Fanie; Anglin, Olivia L. U.; Albert, Arianne; Mayhue, Jazlyn G.; Fairbrother, Nichole
Objective: Unwanted, intrusive thoughts (UITs) of infant related harm are a common postpartum phenomenon and can be classified into thoughts of accidental harm (TAH) and thoughts of intentional harm (TIH). Our study’s objective was to complete a comprehensive, comparative analysis of TAH and TIH by commenting on their prevalence, course, characteristics (time, distress, impairment) and most intense period. Methods: 763 English-speaking pregnant women across British Columbia were recruited to participate in a prospective cohort study. Study data was collected between February 2014 and February 2017. UITs were assessed by semi-structured interviews twice during the postpartum period. Results: The prevalence of TAH and TIH in the postpartum period was 95.8% and 53.9%, respectively. The most common TAH included thoughts of the baby becoming apneic or dying from SIDS; the most common TIH included thoughts of neglect. On average, TAH are more prevalent, time consuming, and result in greater interference compared to TIH. The most intense period for TAH (5.74 weeks postpartum) and TIH (within first 8 weeks postpartum) was identified. During this period, over 40% of participants reported moderate or extreme distress related to UITs. For most, UITs decreased in frequency or completely resolved by 6 months postpartum and most participants did not report clinically significant symptoms. Conclusion: UITs are a normative and typically self-resolving occurrence in the postpartum period. UITs’ most intense period signifies a time of heightened vulnerability. Increased education is necessary to normalize and reduce distress associated with UITs.
Perinatal timing of obsessive-compulsive disorder onset
(Journal of Clinical Psychiatry, 2025) Fairbrother, Nichole; Beck, Quincy M.; Keeney, Cora L.
Objectives: The purpose of this research was to assess timing and characteristics of the onset of perinatally occurring obsessive compulsive disorder (OCD). OCD is a potentially disabling anxiety-related mental health condition for which the perinatal period represents a time of increased risk for onset, recurrence, and exacerbation. Methods: This was a prospective cohort study conducted in British Columbia, Canada. Recruitment took place from January 23, 2014 to September 09, 2016. Participants provided information on reproductive and demographic questionnaires and diagnostic interviews (using the Structured Clinical Interview for DSM-5) in late pregnancy and at two postpartum time points. Only participants who reported symptoms meeting full criteria for OCD during their current perinatal period were included in this report of findings (N = 97). Analyses were primarily descriptive in nature, with Chi-square tests employed to test differences in onset (pregnancy vs. postpartum) and perinatal OCD development based on age first symptom onset (childhood/adolescence vs. adulthood). Results: Over two thirds (71%) of participants whose symptoms met full criteria for OCD at some point in their most recent perinatal period reported perinatal disorder onset. The majority of these (74%) reported onset during their first perinatal period. Perinatal disorder onset was much more likely to occur in the postpartum (83%), compared with in pregnancy (17%), χ2 (1, N = 69) = 29.3, p < .001. Symptom exacerbations were more likely to occur postpartum (77%) compared with prenatally (35%). Further, the lag time from symptom onset to disorder onset was shorter among participants who experienced a perinatal compared with a non-perinatal onset of their OCD. Conclusion: Findings contribute to our understanding of perinatal OCD onset, emphasize the vulnerability to OCD during the perinatal period, and provide one of the first assessments in which symptom onset is distinguished from disorder onset. This work underscores the importance of recognizing the distinct nature of perinatal OCD.
Intersecting gender, ethnicity, and sexual orientation identities and HIV stigma: Results from the People Living with HIV Stigma Index Study in Three Provinces in Canada
(Culture, Health & Sexuality, 2025) Lo Hog Tian, Jason M.; McFarland, Abbey; Penny, Lucas; Bennett, Teresa; Musumbulwa, Kaminda; Watson, James R.; Odhiambo, Apondi J.; Baral, Stefan; Worthington, Catherine; Monteith, Ken; Oliver, Brent; Payne, Michael; Rourke, Sean B.
Stigma remains a significant burden for people living with HIV and while studies have examined the impacts of gender, ethnicity, and sexual orientation on stigma separately, little is known about how these factors may intersect and potentially exacerbate levels of stigma. This study examines how these intersecting social positions may relate to levels of internalised, enacted and anticipated HIV stigma. Participants were recruited in Ontario, Alberta, and Québec (n=1040) as part of the People Living with HIV Stigma Index study in Canada. Three-way interaction models were constructed by creating interaction terms from the product of gender, ethnicity, and sexual orientation variables that predicted each type of stigma. Levels of internalised, enacted and anticipated stigma were consistent across most intersecting groups; however, people occupying certain intersections experienced significantly higher levels of stigma. Three-way interaction analyses showed that for internalised stigma, people at the intersection of African/Caribbean/Black, lesbian, cis-women identities had significantly higher scores (b = 0.90, p=0.06), while people at the intersection of Indigenous, lesbian, and cis-women identities had higher scores for enacted stigma (b = 1.21, p=0.01) compared to the White, heterosexual, cis-men reference group. Interventions designed for populations that take intersectionality into account may be effective in reducing HIV stigma, although more quantitative intersectionality work must be done to understand these implications fully.
Post-abortion aftercare kits
(The Fireweed Project, 2025) Pinan, Astrid Vanessa
The Fireweed Project is providing aftercare kits for Indigenous peoples receiving an abortion in Canada! We created post-abortion support kits based on conversations with Indigenous community members who had an abortion, and expressed how much a thoughtfully crafted aftercare kit would have meant to them during their abortion journey. We are offering these kits (which include things like pads, cramping supplies, self-care and Indigenous-specific items) to those who meet the following criteria: You self-identify as an Indigenous person in Canada (First Nations, Métis, and/or Inuit); You reside in Canada; You are 12 years of age or older; and you have received an abortion within the last year.
In-depth proteome coverage of in vitro-cultured Treponema pallidum and quantitative comparison analyses with in vivo-grown treponemes
(Journal of Proteome Research, 2024) Houston, Simon; Gomez, Alloysius; Geppert, Andrew; Goodyear, Mara C.; Cameron, Caroline E.
Previous mass spectrometry (MS)-based global proteomics studies have detected a combined total of 86% of all Treponema pallidum proteins under infection conditions (in vivo-grown T. pallidum). Recently, a method was developed for the long-term culture of T. pallidum under in vitro conditions (in vitro-cultured T. pallidum). Herein, we used our previously reported optimized MS-based proteomics approach to characterize the T. pallidum global protein expression profile under in vitro culture conditions. These analyses provided a proteome coverage of 94%, which extends the combined T. pallidum proteome coverage from the previously reported 86% to a new combined total of 95%. This study provides a more complete understanding of the protein repertoire of T. pallidum. Further, comparison of the in vitro-expressed proteome with the previously determined in vivo-expressed proteome identifies only a few proteomic changes between the two growth conditions, reinforcing the suitability of in vitro-cultured T. pallidum as an alternative to rabbit-based treponemal growth. The MS proteomics data have been deposited in the MassIVE repository with the data set identifier MSV000093603 (ProteomeXchange identifier PXD047625).
Canadian network for mood and anxiety treatments 2024 clinical practice guideline for the management of perinatal mood, anxiety and related disorders
(Canadian Journal of Psychiatry, 2025) Vigod, Simone N.; Frey, Benicio; Clark, Crystal T.; Grigoriadis, Sophie; Barker, Lucy C.; Brown, Hilary K.; Charlebois, Jaime; Dennis, Cindy Lee; Fairbrother, Nichole; Green, Sheryl; Letourneau, Nicole L.; Oberlander, Tim F.; Sharma, Verinder; Singla, Daisy R.; Stewart, Donna E; Tomasi, Patricia; Ellington, Brittany D.; Fleury, Cathleen; Tarasoff, Lesley A.; Tomfohr-Madsen, Lianne; Da Costa, Deborah; Beaulieu, Serge; Brietzke, Elisa; Kennedy, Sidney H.; Lam, Raymond W.; Milev, Roumen V.; Parikh, Sagar V.; Ravindran, Arun V.; Samaan, Zainab; Schaffer, Ayal; Taylor, Valerie H.; Tourjman, Smadar V.; Van Ameringen, Michael; Yatham, Lakshmi N.; Van Lieshout, Ryan J.
Background The Canadian Network for Mood and Anxiety Treatments (CANMAT) publishes clinical practice guidelines for mood and anxiety disorders. This CANMAT guideline aims to provide comprehensive clinical guidance for the pregnancy and postpartum (perinatal) management of mood, anxiety and related disorders. Methods CANMAT convened a core editorial group of interdisciplinary academic clinicians and persons with lived experience (PWLE), and 3 advisory panels of PWLE and perinatal health and perinatal mental health clinicians. We searched for systematic reviews of prevention and treatment interventions for perinatal depressive, bipolar, anxiety, obsessive–compulsive and post-traumatic stress disorders (January 2013–October 2023). We prioritized evidence from reviews of randomized controlled trials (RCTs), except for the perinatal safety of medications where reviews of large high-quality observational studies were prioritized due to the absence of RCT data. Targeted searches for individual studies were conducted when systematic reviews were limited or absent. Recommendations were organized by lines of treatment based on CANMAT-defined levels of evidence quality, supplemented by editorial group consensus to balance efficacy, safety, tolerability and feasibility considerations. Results The guideline covers 10 clinical sections in a question-and-answer format that maps onto the patient care journey: case identification; organization and delivery of care; non-pharmacological (lifestyle, psychosocial, psychological), pharmacological, neuromodulation and complementary and alternative medicine interventions; high-risk clinical situations; and mental health of the father or co-parent. Equity, diversity and inclusion considerations are provided. Conclusions This guideline's detailed evidence-based recommendations provide clinicians with key information to promote the delivery of effective and safe perinatal mental healthcare. It is hoped that the guideline will serve as a valuable tool for clinicians in Canada and around the world to help optimize clinical outcomes in the area of perinatal mental health.
Proteomic analysis of the Treponema pallidum subsp. pallidum ss14 strain: Coverage and comparison with the Nichols strain proteome
(Frontiers in Microbiology, 2024) Houston, Simon; Marshall, Steven; Gomez, Alloysius; Cameron, Caroline E.
Introduction: Strains of the syphilis spirochete, Treponema pallidum ssp. pallidum, group into one of two deep-branching clades: the Nichols clade or the globally dominant Street Strain 14 (SS14) clade. To date, in-depth proteome-wide analyses have focused on Nichols clade strains. Methods: The T. pallidum SS14 clade reference strain (SS14) proteome was characterized via protein detection and quantification analyses using mass spectrometry, and comparison was made to the Nichols clade reference strain (Nichols) proteome. Results: Approximately two thirds of all proteins from T. pallidum SS14 were detected and quantitated, allowing confirmation of expression of 259 proteins for the first time in this strain, including 11 known/putative outer membrane proteins (OMPs). SS14 and Nichols proteome comparative analyses demonstrated similar protein expression/quantification profiles between the two strains, and showed that inter-strain amino acid sequence differences are located primarily within predicted surface-exposed regions in 16 known/putative OMPs. Discussion: This study provides the first comparative analyses of the proteomes from the T. pallidum SS14 and Nichols strains. The findings inform syphilis vaccine design by confirming the expression of known/predicted OMP vaccine candidates in SS14 treponemes, and via the finding that most inter-strain variable residues found in OMPs are predicted to be located in surface-exposed, host-facing regions of these proteins.
Syphilis vaccine development: Aligning vaccine design with manufacturing requirements
(Human Vaccines & Immunotherapeutics, 2024) Waugh, Sean; Cameron, Caroline E.
Syphilis, caused by Treponema pallidum subsp. pallidum, is a global health concern with increasing rates worldwide. Current prevention strategies, including screen-and-treat approaches, are not sufficient to resolve rising infection rates, emphasizing the need for a vaccine. Developing a syphilis vaccine necessitates a range of cross-disciplinary considerations, including essential disease-specific protection, technical requirements, economic feasibility, manufacturing constraints, public acceptance, equitable vaccine access, alignment with global public vaccination programs, and identification of essential populations to be vaccinated to achieve herd immunity. Central to syphilis vaccine development is prioritization of global vaccine availability, including access in low- to middle-income settings. Various vaccine platforms, including subunit, virus-like particle (VLP), mRNA, and outer membrane vesicle (OMV) vaccines, present both advantages and challenges. The proactive consideration of both manufacturing feasibility and efficacy throughout the pre-clinical research and development stages is essential for producing an efficacious, inexpensive, and scalable syphilis vaccine to address the growing global health burden caused by this disease.
Identification of antibodies induced by immunization with the syphilis vaccine candidate Tp0751
(Vaccine, 2025) Urselli, Francesca; Gomez, Alloysius; Gray, Matthew D.; Cameron, Caroline E.; Taylor, Justin J.
The continued and increasing prevalence of syphilis worldwide highlights the need for an effective syphilis vaccine to complement public health measures. Previous work demonstrated that immunization of the rabbit animal model with vaccine candidates derived from the T. pallidum endothelial cell adhesin Tp0751 could reduce dissemination of T. pallidum to lymph nodes. In those studies, a proportion of animals exhibited complete inhibition of treponemal dissemination and others exhibited partial or no inhibition of treponemal dissemination, consistent with results expected from an outbred animal model. In the current study we further characterized the Tp0751-specific antibody response in immunized animals that showed inhibition of T. pallidum dissemination. To do this, we generated Tp0751 tetramers to identify Tp0751-specific B cells before and after immunization. Using this approach, we found a robust expansion of Tp0751-specific B cells in the blood and spleens of immunized animals compared to unimmunized control animals. Ten antibodies from Tp0751-immunized rabbits were cloned and binding to specific structural regions of the Tp0751 protein was assessed using epitope mapping assays and structural modeling. Importantly, nine out of the ten antibodies cloned from Tp0751 tetramer-binding B cells were able to significantly inhibit T. pallidum attachment to human endothelial cells in vitro, including antibodies exhibiting weaker binding to Tp0751. Combined, our results provide a proof-of-principle that Tp0751-based subunit vaccines can stimulate strong B cell responses resulting in the production of antibodies able to inhibit T. pallidum attachment to endothelial cells.
Treponema pallidum induces pro-inflammatory cytokine secretion in macrophages and macrophage-endothelial co-cultures
(Frontiers in Cellular and Infection Microbiology, 2025) Waugh, Sean; Ranasinghe, Akash; Reynolds, Lisa A.; Cameron, Caroline E.
Syphilis, caused by the extracellular bacterium Treponema pallidum ssp. pallidum, is a multi-stage and systemic infection that is lifelong in the absence of treatment. Two host cell types that frequently encounter T. pallidum during infection are endothelial cells and macrophages; treponemes disseminate through the vasculature and cross the blood–brain and placental barriers by traversing endothelial cell barriers, and macrophages are known to be critical for clearance of T. pallidum. Despite the importance of macrophages in treponemal clearance and endothelial cells in treponemal dissemination, a comprehensive understanding of the cytokines secreted by T. pallidum-exposed macrophages in the presence and absence of endothelial cells has not yet been achieved. To address this knowledge gap, we conducted time-course cytokine secretion profiling of macrophage-differentiated THP-1 cells alone and in co-culture with human brain microvascular endothelial cells. These experiments revealed reduced IL-8 secretion and increased secretion of RANTES, soluble ICAM-1, IL-1?, MCP-1, GM-CSF, TNF, and IL-6 in T. pallidum-exposed macrophage monocultures and macrophage-endothelial cell co-cultures compared to the same culture conditions in the absence of T. pallidum. These investigations enhance our understanding of macrophage-mediated, T. pallidum-focused innate immune responses occurring at endothelial sites. Further, this study provides insight into pro-inflammatory mechanisms elicited after exposure to this pathogen that may contribute to endothelial junction disruption, T. pallidum dissemination, and syphilis symptoms.
New pathways in syphilis vaccine development
(Sexually Transmitted Diseases, 2024) Liu, Andy; Giacani, Lorenzo; Hawley, Kelly L.; Cameron, Caroline E.; Seña, Arlene C.; Konda, Kelika A.; Radolf, Justin D.; Klausner, Jeffrey D.
The New Pathways in Syphilis Vaccine Development meeting was held before the start of the STI & HIV 2023 World Congress as a pre-meeting symposium to highlight recent advances in the development of an effective syphilis vaccine and discuss the challenges still faced by investigators. Internationally renowned public health officials, clinical investigators, and basic researchers from academia, government, and community-based organizations met on July 24, 2023, in Chicago, Illinois. Four speakers discussed key research findings in syphilis vaccine development, which included antigen selection, identification of epitopes associated with protective immunity, and delivery platforms, with great emphasis on development of chimeric antigens. Significant progress was also shown on the elucidation of Treponema pallidum genomes from virtually all continents to assess the diversity in vaccine candidates of the syphilis spirochete.
The relationship of childhood maltreatment, adult sexual victimization, depressed mood and symptoms of trauma with fear of childbirth
(Journal of Affective Disorders, 2025) Fairbrother, Nichole; Keeney, Cora; Mao, Yue; Beck, Quincy M.
Background: Fear of childbirth (FoB) is experienced to some degree by most pregnant people and can be intense enough to merit treatment. Despite significant research on the topic of FoB, studies investigating various forms of maltreatment and mental health symptoms in relation to FoB are very limited. In particular, studies including multiple forms of maltreatment along with mental health symptoms as predictors of FoB are extremely limited. We sought to fill this gap and clarify the relative contributions of these variables to the prediction of FoB. Methods: This was a secondary analysis of data from pregnant people in Canada. Participants (N = 881) provided demographic and reproductive history information, completed self-report measures of FoB, childhood maltreatment (multiple forms), adult sexual victimization, depressed mood and symptoms of posttraumatic stress disorder (PTSD). They were also administered a diagnostic interview to assess for specific phobia, FoB. Analyses included descriptive information, Wilcoxon rank sum tests, linear and logistic regression, and path analysis. Results: Most forms of maltreatment showed some association with increased FoB. However, when assessed together, only emotional maltreatment remained a significant predictor of FoB. Both depressed mood and symptoms of PTSD contributed more to FoB than maltreatment, and mediated the relationship of emotional maltreatment with FoB. The only direct effects of childhood emotional maltreatment on FoB were for fears of medical interventions and feelings of embarrassment during labour and delivery. Limitations: Study findings fill significant gaps in our understanding of the relationship between maltreatment, mental health symptoms and FoB. However, the study sample was limited to Canadian participants, most of whom were socio-economically advantaged, cis-gender women of European descent, thus limiting the generalizability of the findings. Further, as childhood maltreatment and sexual assault experiences in adulthood were reported retrospectively, study findings are also vulnerable to recall bias. Conclusions: Findings contribute to our understanding of the relationship between childhood maltreatment, adult sexual victimization, mental health and FoB. These findings can facilitate future research and improved care via a focus on depressed mood, symptoms of PTSD, emotional maltreatment and specific fears of medical interventions and social discomfort as significant contributors to one's experience of FoB.
Time-course transcriptomics reveals the impact of Treponema pallidum on microvascular endothelial cell function and phenotype
(Frontiers in Microbiology, 2025) Waugh, Sean; Goodyear, Mara C.; Gomez, Alloysius; Ranasinghe, Akash; Lithgow, Karen V.; Falsafi, Reza; Hancock, Robert E. W.; Lee, Amy H.; Cameron, Caroline E.
Syphilis, caused by Treponema pallidum subsp. pallidum, is an urgent global public health threat. Syphilis vaccine development has been impeded by limited understanding of the molecular mechanisms that enable T. pallidum to establish and maintain infection. The vascular endothelium is critical for T. pallidum attachment, dissemination, and host immune response initiation; however, the molecular details of T. pallidum-endothelial interactions are incompletely understood. To enhance understanding, we performed time-course transcriptomic profiling on T. pallidum-exposed brain microvascular endothelial cells. These analyses showed T. pallidum exposure altered pathways related to extracellular matrix, growth factors, integrins, and Rho GTPases. The induced transcriptional response was consistent with endothelial to mesenchymal transition, a process involved in fetal development and vascular dysfunction. In cells exposed to T. pallidum, the primary transcription factor associated with this process (Snail) was increased at both the transcript and protein levels, and microscopy analyses demonstrate F-actin cellular contraction. This study provides a comprehensive understanding of the molecular responses of endothelial cells to T. pallidum and identified the host pathways that might cause syphilis disease symptoms, information that could aid in syphilis vaccine design.
Anxiety and related disorders during the perinatal and postpartum periods
(Annual Review of Clinical Psychology, 2025) Fairbrother, Nichole; Challacombe, Fiona L.; Green, Sheryl M.; O'Mahen, Heather A.
Anxiety and anxiety-related disorders are, as a group, the most common mental health conditions and are more common among women compared with among men. It is now evident that these disorders affect one in five pregnant and postpartum people and are more common than depression. For some disorders (e.g., obsessive–compulsive disorder), there is also evidence of an elevated risk for their development and exacerbation during perinatal periods. In this article, we review the literature pertaining to anxiety and anxiety-related disorders during the perinatal period. We also provide information related to pregnancy-specific anxiety and fear of childbirth constructs that exist outside of diagnostic classification but are particularly important in the perinatal context. We review the scope, prevalence, and etiology of these disorders as well as comorbidity, screening, assessment, and treatment. We conclude with an overview of some of the key gaps in knowledge and recommendations for future research.
DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies using in vitro tools
(bioRxiv, 2025) Garcia, Leandro E.; Lin, Zitong; Culos, Sophie; Muenker, M Catherine; Johnson, Emily E.; Wang, Zheng; Lopez-Giraldez, Francesc; Giraud-Gatineau, Alexandre; Jackson, Angela; Picardeau, Mathieu; Goodlett, David R.; Townsend, Jeffrey P.; Pětrošová, Helena; Wunder, Elsio A., Jr.
Pathogenic Leptospira species can survive and thrive in a wide range of environments. Distinct environments expose the bacteria to different temperatures, osmolarities, and amounts and sources of nutrition. However, leptospires are mostly cultured, in a laboratory setting under in vitro conditions that do not reflect natural environments. This constraint on laboratory cultures limits the applicability of in vitro studies to the understanding of even simple pathogenic processes. Here we report, investigate, and identify a medium and conditions that mimic the host environment during leptospirosis infection, expanding the available in vitro tools to evaluate leptospiral pathogenesis. We quantified genome-wide gene expression of pathogenic Leptospira interrogans cultured in different in vitro media compositions (EMJH, DMEM, EMEM, and HAN). Using EMJH as standard, we compared gene expression in these compositions to genome-wide gene expression gathered in a host environment: whole blood (WB) of hamsters after infection with pathogenic leptospires. Leptospires cultured in DMEM and EMEM media shared 40% and 47% of all differentially expressed genes (DEGs) of leptospires present within WB (FDR<0.01), while leptospires cultured in HAN media only shared 20% of DEGs with those from WB. Furthermore, gene and pathway expression of leptospires cultured on DMEM and EMEM media exhibited a better correlation with leptospires grown in WB, including promoting expression of a similar leptospiral lipid A profile to the one identified directly in host tissues. Taken together, these results indicate that commercial cell-culture media EMEM or DMEM are better surrogates for in vivo pathogenic studies than EMJH or HAN media in Leptospira. These alternative culture conditions, using media that are a standard supply worldwide, provide a reproducible and cost-effective approach that can accelerate research investigation and reduce the number of animal infections necessary for basic research of leptospirosis.
Novel insights into the distribution and effects of perfluorooctanesulfonic acid (PFOS) in the nervous system of a frog tadpole model by mass spectrometry imaging
(Environmental Science & Technology, 2026) Poulsen, Rikke; Field, Emma M.; Jackson, Angela M.; Kuecks-Winger, Haley; Thambirajah, Anita A.; Goodlett, David R.; Helbing, Caren C.; Pětrošová, Helena
Determining how environmental contaminants localize within tissues is essential for understanding the consequences of sublethal exposures. Therefore, we optimized a mass spectrometry imaging (MSI) workflow to study the distribution and biological effects of contaminants in an environmentally relevant frog tadpole model. We applied the method to the entire tadpole head postexperimental exposure to the legacy contaminant, perfluorooctanesulfonic acid (PFOS; 0.1–100 ?g/L, 48 h). At 10 ?g/L, PFOS unexpectedly localized mainly to the olfactory epithelium. At 100 ?g/L, PFOS was distributed throughout all tissues except for the brain, where only the pineal gland showed significant accumulation. The pineal gland, a neuroendocrine organ regulating the circadian rhythm, is not protected by the blood–brain barrier. Together, these findings indicate that PFOS did not readily cross the blood–brain barrier. In both the olfactory epithelium and pineal gland, effects of PFOS were reflected in changes in the abundances of endogenous lipids. The results open questions for the most adverse outcomes of PFOS exposure, including effects on the olfactory-mediated behavior and circadian rhythm. The present study exemplifies how MSI advances our analytical toolbox. The ability to localize contaminants within biological compartments is critical for the characterization of their toxic effects and risks to wildlife and humans.
Reappraising the relationship between hyperinsulinemia and insulin resistance in PCOS
(Journal of Endocrinology, 2025) Houston, Emma J.; Templeman, Nicole M.
Polycystic ovary syndrome (PCOS), a reproductive endocrine disorder with quintessential features of metabolic dysfunction, affects millions of women worldwide. Hyperinsulinemia (i.e., elevated insulin without hypoglycemia) is a common metabolic feature of PCOS that worsens its reproductive symptoms by exacerbating pituitary hormone imbalances and increasing levels of bioactive androgens. Hyperinsulinemia in PCOS is often attributed to insulin resistance, based on the concept that impaired insulin-mediated glucose disposal would induce compensatory insulin hypersecretion. However, it is challenging to define the sequential relationship between insulin sensitivity and insulin secretion, as they are tightly interlinked, and evidence suggests that hyperinsulinemia can alternatively precede insulin resistance. Notably, other drivers of hyperinsulinemia (outside of insulin resistance) may be highly relevant in the context of PCOS. For instance, high androgen levels can augment both hyperinsulinemia and insulin resistance, generating a self-perpetuating cycle of reproductive and metabolic dysfunction. In this review, we evaluate the cause-and-effect relationships between insulin resistance and hyperinsulinemia in PCOS. We examine evidence for the prevailing theory of insulin resistance as the primary defect that causes secondary compensatory hyperinsulinemia, and an alternative framework of hyperinsulinemia as the earlier defect that perpetuates reproductive and metabolic features of PCOS. Considering the heterogeneous nature of PCOS, it is improbable that its metabolic characteristics always follow the same progression. Comprehensively examining all mechanistic regulators of hyperinsulinemia and insulin resistance in PCOS might thereby lead to improved prevention and management strategies, and address critical knowledge gaps in the progression of PCOS pathogenesis.
Proteomic changes in cancer cell lines as a result of bacterial infection
(Proteomics, 2025) Ren, Bo; Weke, Kenneth; Hardie, Darryl; Goncheva, Mariya I.; Hupp, Ted; Alfaro, Javier Antonio; Pětrošová, Helena; Goodlett, David R.
Bacterial infections have been implicated in shaping the tumor microenvironment (TME), but their effects on cancer cell proteomes remain unexplored. In this study, we analyzed proteomic changes in melanoma (A375) and ovarian cancer (OVCAR3) cell line models following infection with Staphylococcus aureus strain USA300 or Salmonella enterica strain SL1344 using mass spectrometry-based label-free quantitative proteomics. Bacterial infection leads to widespread changes in host protein expression in the cancer cells, with levels of proteins involved in mitochondrial metabolism, RNA processing, and cellular stress response all increasing in relative abundance. In contrast, proteins involved in DNA repair, cytoskeletal structure, vesicle trafficking, and cell cycle regulation were consistently downregulated. The magnitude of the observed changes varied by the cancer cell type. Understanding these interactions may provide new directions for the role of bacteria in tumor progression and therapeutic resistance.
The aesthetic labour of polycystic ovarian syndrome: The strife of heteronormative standards and the possibilities of queering sexualities
(Sexualities, 2025) Cacchioni, Thea
This article contributes to the burgeoning qualitative literature on experiences of Polycystic Ovarian Syndrome (PCOS) by considering PCOS in relation to post-structural theory on gender, sexuality, embodiment, and aesthetic labour. Although to some degree culturally contingent, interview accounts with 30 people diagnosed with PCOS suggest that infertility, hairiness, acne, and/or fatness are a difficult combination with heterosexuality and a source of stigma regardless of identity. This article outlines the aesthetic labour women engaged in to meet heterosexual standards, highlighting structure, and where possible, agency in this work. It also highlights the potential of queer relationships, communities, and perspectives to disrupt heteronormative pressures, considering the promise and limits of bodily acceptance
Glucose enrichment accelerates C. elegans reproductive aging via non-autonomous DAF-2/insulin-like receptor signaling in somatic tissues
(bioRxiv, 2025) Athar, Faria; Houston, Emma J.; Jewett, Emily; Templeman, Nicole M.
Detrimental effects of chronic high-sugar overconsumption can extend from molecular and cellular responses to systemic changes. Reproductive systems are particularly sensitive to diet and energetic state, yet the long-term reproductive consequences of overnutrition are poorly defined. Here, we used Caenorhabditis elegans to study the impacts of glucose excess on reproductive aging. Glucose supplementation shortens C. elegans lifespan, and we found that it also hastens age-related reproductive decline, evidenced by a greater deterioration in oocyte quality and lower fertility with age. We next evaluated insulin-like signaling contributions, as this glucose-responsive pathway is well known to regulate both somatic aging and reproductive aging. Intriguingly, while 20 mM glucose enrichment still shortens the lifespan of daf-2(e1370) mutants, we found that it had no detrimental impact on their reproductive aging phenotypes. Using auxin-induced tissue-selective degradation, we discovered that DAF-2/insulin-like receptor signaling in C. elegans intestine and body wall musculature is required for glucose enrichment to exert damaging impacts on the reproductive system. However, suppressing insulin-like signaling in either of these tissues is sufficient to protect C. elegans against glucose-induced reproductive aging. These findings suggest that insulin-like signalling in metabolically active somatic tissues may represent a key link between overnutrition and reproductive aging.

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