David M Olson

• Ph.D., FRCOG
• Professor at University of Alberta

Intrauterine inflammation is a significant cause of early preterm birth and fetal injury. There is a lack of effective interventions for intrauterine inflammation. This study aimed to determine whether direct fetal treatment with IL-1 receptor antagonists (IL-1RA), specifically anakinra (competitive IL-1RA) or rytvela (allosteric IL-1RA), could red...

Background Each mother–child dyad represents a unique combination of genetic and environmental factors. This constellation of variables impacts the expression of countless genes. Numerous studies have uncovered changes in DNA methylation (DNAm), a form of epigenetic regulation, in offspring related to maternal risk factors. How these changes work t...

Background Perinatal infection/inflammation is associated with a high risk for neurological injury and neurodevelopmental impairment after birth. Despite a growing preclinical evidence base, anti-inflammatory interventions have not been established in clinical practice, partly because of the range of potential targets. We therefore systematically r...

Background: Intraamniotic inflammation is associated with preterm birth, especially in cases occurring before 32 weeks' gestation, and is causally-linked with increased risk of neonatal mortality and morbidity. Targeted anti-inflammatory interventions may assist in improving outcomes for pregnancies impacted by intrauterine inflammation. Interleuk...

Background: Genome-wide DNA methylation (DNAme) profiling of the placenta with Illumina Infinium Methylation bead arrays is often used to explore the connections between in utero exposures, placental pathology, and fetal development. However, many technical and biological factors can lead to signals of DNAme variation between samples and between co...

Prenatal maternal stress and mental health problems are known to increase risk for developmental psychopathology in offspring, yet pathways leading to risk or resiliency are poorly understood. In a quasi-experimental design, we prospectively examined associations between disaster-related prenatal stress, maternal mental health symptoms, and infant...

Background Despite the existing knowledge about stress, trauma and pregnancy and maternal stress during natural disasters, little is known about what types of trauma pregnant or preconception women experience during these disasters. In May 2016, the worst natural disaster in modern Canadian history required the evacuation of nearly 90,000 residents...

Prenatal maternal stress is linked to adverse pregnancy and infant outcomes, including shortened gestation lengths, low birth weights, cardio-metabolic dysfunction, and cognitive and behavioural problems. Stress disrupts the homeostatic milieu of pregnancy by altering inflammatory and neuroendocrine mediators. These stress-induced phenotypic change...

Background: Preterm birth is the leading cause of neonatal morbidity and mortality. Studies have shown that interleukin-1 plays a major role in the pathophysiology of preterm birth participating by inducing the production of pro-inflammatory mediators and uterine activating proteins leading to labor. More importantly, uteroplacental inflammation,...

Important factors influencing the outcome of animal experiments in preclinical research are often overlooked. In the current study, the reaction of female and male rats toward the biological sex of a human experimenter was investigated in terms of anxiety-like behaviors and physiological stress responses, as measured by infrared (IR) thermography,...

Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long–Evans rats exposed to social isolation stress...

Neutrophils and other leukocytes invade the mouse uterus at term birth, which is normal for activating the uterus for labor. To better understand the regulation of this migration at term and interleukin (IL)-1β—induced preterm birth, we developed a mouse leukocyte migration assay (mLMA) and used it with rytvela, an IL-1 receptor allosteric antagoni...

Background On May 3, 2016, residents of Fort McMurray Wood Buffalo, Alberta were evacuated due to an uncontrolled wildfire. The short-notice evacuation had destabilizing consequences for residents, including changes in routines, loss of control, and increased uncertainty. These consequences were especially detrimental to women who were pregnant or...

Background Intraamniotic inflammation is associated with up to 40% of preterm births, most notably in deliveries occurring prior to 32 weeks’ gestation. Despite this, there are few treatment options allowing the prevention of preterm birth and associated fetal injury. Recent studies have shown that the small, non-competitive allosteric interleukin...

In preparation for delivery, the uterus transitions from actively maintaining quiescence during pregnancy to an active parturient state. This transition occurs as a result of the accumulation of pro-inflammatory signals which are amplified by positive feedback interactions involving paracrine and autocrine signaling at the level of each intrauterin...

Introduction The resilience of Canadian military families (CMFs) – the main support of the Canadian Armed Forces service members (SMs) – is imperative. The Canadian Armed Forces aims to ensure that SMs and their families are resilient and SMs ready to respond when called upon for combat, peacekeeping or pandemic/disaster-response. Family concerns,...

Preterm birth (PTB) remains the leading cause of infant morbidity and mortality. Despite 50 years of research, therapeutic options are limited and many lack clear efficacy. Tocolytic agents are drugs that briefly delay PTB, typically to allow antenatal corticosteroid administration for accelerating fetal lung maturity or to transfer patients to hig...

Introduction: Data show that maternal stress triggered by exposure to a natural disaster before, during or just after pregnancy is associated with adverse pregnancy and newborn outcomes. In this paper, the first aim is to describe our efforts to test a simple, low-cost intervention to large numbers of women following a major natural disaster. The s...

Introduction: A new vision of resilience and well-being for Canadian military service members (SMs), Veterans and their families has been championed by the Canadian Armed Forces (CAF) and Veterans Affairs Canada (VAC). Operationalizing this vision, which aims to support those who serve/have served and their families as they navigate life during and...

The Problem: Global environmental stressors of human health include, but are not limited to, conflict, migration, war, natural disasters, climate change, pollution, trauma, and pandemics. In combination with other factors, these stressors influence physical and mental as well as reproductive health. Maternal stress is a known factor for adverse pre...

Background Expressive writing requires journaling stressor-related thoughts and feelings over four daily sessions of 15 min. Thirty years of research have popularized expressive writing as a brief intervention for fostering trauma-related resilience; however, its ability to surpass placebo remains unclear. This study aimed to determine the efficacy...

Preterm birth (PTB) and its consequences are a major public health concern as preterm delivery is the main cause of mortality and morbidity at birth. There are many causes of PTB, but inflammation is undeniably associated with the process of premature childbirth and fetal injury. At present, treatments clinically available mostly involve attempt to...

Background Inflammation and particularly interleukin-1β (IL-1β), a pro-inflammatory cytokine highly secreted by activated immune cells during early AMD pathological events, contribute significantly to retinal neurodegeneration. Here, we identify specific cell types that generate IL-1β and harbor the IL-1 receptor (IL-1R) and pharmacologically valid...

Objective: Following disasters, perinatal women are vulnerable to developing posttraumatic stress disorder (PTSD)-like symptoms. Little is known about protective factors. We hypothesized that peritraumatic stress would predict PTSD-like symptoms in pregnant and postpartum women and would be moderated by social support and resilience. Method: Women...

The climate crisis is the existential threat of our times and for generations to come. This is no longer a threat but a reality affecting us, our children, and the generations that follow. Pregnant mothers, their fetuses, and their children are among those at greatest risk in every population and every jurisdiction. A timely consideration is the he...

The worst disaster of natural origin in recent Canadian history occurred in May 2016 in the northern Alberta community of Fort McMurray Wood Buffalo (FMWB). Among the 88,000 people abruptly evacuated amidst a raging wildfire were approximately 1850 pregnant or pre-conception women. Based on the Allostatic Load and Preterm Birth Conceptual Framework...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Every year, 15 million pregnancies end prematurely, resulting in more than 1 million infant deaths and long‐term health consequences for many children. The physiological processes of labour and birth involve essential roles for immune cells and pro‐inflammatory cytokines in gestational tissues. There is compelling evidence that the mechanisms under...

Maternal stress is a well-established risk factor for preterm birth and has been associated with adverse neonatal outcomes in the first and subsequent generations, including increased susceptibility to disease and lasting immunological changes. However, a causal link between prenatal maternal stress and preterm birth, as well as compromised neonata...

Preterm birth (PTB) has a complex etiology that includes genetic heritability, lifestyle and health, socioeconomic status, and psychosocial stress. Racial disparities in pregnancy outcomes are reported in many countries, but an especially marked contrast is evident in the United States. Because of the size of the problem, considerable research has...

Introduction Maternal gestational stress and immune activation have independently been associated with affective and neurodevelopmental disorders across the lifespan. We investigated whether rats exposed to prenatal maternal stressors (PNMS) consisting of psychological stress, interleukin (IL)-1β or both (two-hit stress) during critical development...

Determinants of lifetime health are complex and emphasize the need for robust predictors of disease risk. Allostatic load (AL) has become a clinical framework to estimate the cumulative biological burden associated with chronic stress. To assist knowledge translation in the developmental origins of health and disease field, clinically valid methods...

Complex cellular and physiological interactions are required to prepare the uterus for birth. The change from the state of pregnancy to the state of parturition, which we call uterine transitioning, requires the actions of inflammatory mediators and results in an activated uterus capable of performing the physiology of labour. Interleukin (IL)-1β a...

Maternal stress and inflammation excesses can lead to adverse pregnancy outcomes and offspring development. We evaluated whether distinct prenatal stressors affect pregnancy, maternal and offspring outcomes and uterine gene expression differently when combined than either alone. Long-Evans dams were exposed to psychological or/and (two-hit) immune...

Birth is a complex biological event requiring genetic, cellular and physiological changes to the uterus, resulting in a uterus activated for completing the physiological processes of labor. We define the change from the state of pregnancy to the state of parturition as uterine transitioning, which requires the actions of inflammatory mediators and...

Antenatal inflammation as seen with chorioamnionitis is harmful to foetal/neonatal organ development including to eyes. Although the major pro-inflammatory cytokine IL-1β participates in retinopathy induced by hyperoxia (a predisposing factor to retinopathy of prematurity), the specific role of antenatal IL-1β associated with preterm birth (PTB) in...

Introduction: Maternal stress and inflammation are increasingly recognized as important factors contributing to pregnancy and offspring developmental outcomes. Our prior work showed that when pregnant rats are exposed to psychological and immune stress, combination of both increases variation in gestational length, reduces maternal F0 and offspring...

Background: Maternal stress not only affects pregnancy and parturition, it also impacts postpartum maternal behavior and offspring neurodevelopment. Rodents as altricial species are especially sensitive to alterations in their mother’s behavior, which may function as an additional stressor. Both gestational and early life stress are known to induce...

Background: Maternal stress and inflammation affect pregnancy, parturition and long-term outcomes, including for offspring. Inflammation, particularly Interleukin (IL)-1, was shown to play a key role in progeny neonatal and developmental outcomes. Objective: We hypothesized that distinct stress hits influence pregnant rats and their offspring diffe...

Introduction: Maternal stress and inflammation are recognized as important contributors to pregnancy and offspring outcomes. Previously we showed that exposing pregnant rats to two-hit stress leads to increased gestational length variation and reduces maternal F0/offspring F1 weight gain. We proposed that stressors exert differential effects on F0...

This interdisciplinary study details spiritual approaches including meditation and yoga shown to be helpful in improving physical and psychological well-being. Whether a person suffers from a psychological or physical malady, such as depression, addictions, chronic pain, cancer, or complications from pregnancy, the best practice treatments likely i...

Stress is a primary risk factor for psychiatric disorders. However, it is not fully understood why some stressed individuals are more vulnerable to psychiatric disorders than others. Here, we investigated whether multigenerational ancestral stress produces phenotypes that are sensitive to depression-like symptoms in rats. We also examined whether s...

Inflammation at the maternal-fetal interface has been shown to be involved in the pathogenesis of preterm birth. Interleukin 27 (IL-27), a heterodimeric cytokine, is known to mediate an inflammatory response in some pregnancy complications. In this study, we aimed to determine whether IL-27 could induce an inflammatory reaction at the maternal-feta...

Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and surviving infants are at increased risks of lifelong complications. PTB has been firmly linked to inflammation regardless of infection, specific aetiology or timing of birth. Deleterious inflammation is observed in maternal and fetal tissue, and correlates wit...

Preeclampsia (PE) is currently thought to be characterized by oxidative stress which may lead to endothelial dysfunction. The normal function of vascular endothelium is essential to vascular homeostasis. Previous studies have shown that steroid receptor coactivator 3 (SRC-3) interacts with estrogen receptors (ERs) which are involved in the vasoprot...

Abstract presented as short oral presentation and poster at the 2nd European Spontaneous Preterm Birth Congress in Gothenburg, Sweden. May 26-28, 2016 Award for Best Short Oral Presentation

Background: Maternal stress and inflammatory mediators are major influencers of the birth process. Prenatal stress increases the number of adverse pregnancy outcomes (APOs), including preterm birth, the leading cause of neonatal and infant morbidity and mortality. We demonstrated that stress can be transmitted across generations influencing both pr...

Abstract as submitted in October 2016 with preliminary analyses. Results presented after more rigourous statistical testing. Potential role for cytokines in adverse pregnancy outcomes (APOs) in a rat 2-hit stress model. Introduction: Maternal stress and inflammatory mediators interact to affect the birth process. In our 2-hit stress model parental...

Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target fetal inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central and is sufficient to trigger fetal loss. Therefore, we elucidated the effects of antenatal IL-1 exposure on postnatal development and inves...

Background Parturition at term and preterm is characterized by sterile inflammatory processes occurring in the absence of infection whereby peripheral leukocytes infiltrate gestational tissues in response to chemotactic signals. In response to a homing signal, recruited leukocytes undergo diapedesis and extravasate through capillaries, migrating in...

Toll-like receptor 4 (TLR4) activation by bacterial infection, or by sterile inflammatory insult is a primary trigger of spontaneous preterm birth. Here we utilize mouse models to investigate the efficacy of a novel small molecule TLR4 antagonist, (+)-naloxone, the non-opioid isomer of the opioid receptor antagonist (−)-naloxone, in infection-assoc...

Uterine labor requires the conversion of a quiescent (pro-pregnancy) uterus into an activated (pro-labor) uterus, with increased sensitivity to endogenous uterotonic molecules. This activation is induced by stressors, particularly inflammation in term and preterm labor. Neuromedin U (NmU) is a neuropeptide known for its utero-contractile effects in...

The role of interleukin-1 (IL-1), a pro-inflammatory cytokine, in parturition is typically noted by changes in its concentrations. Studying the expression of its receptor family, IL-1 receptor (IL-1R) 1, IL-1R2, IL-1R accessory protein (IL-1RAcP), and its predominantly brain isoform, IL-1RAcPb, during late gestation in the uterus in the Long-Evans...

The heterogeneity of spontaneous preterm birth (SPTB) requires an interdisciplinary approach to determine potential predictive risk factors of early delivery. The aim of this study was to investigate maternal whole blood gene expression profiles associated with spontaneous preterm birth (SPTB, <37 weeks) in asymptomatic pregnant women. The study po...

limma outputs for analyses between SPTB and term delivery at (1) T1 or (2) T2; genes displaying temporal changes between T1 and T2 in (3) SPTB or (4) term delivery; and (5) genes whose fold change from 17–23 to 27–33 weeks thatwere different between SPTB and term delivery. (XLSX)

Microarray and quantitative real time-PCR of 13 unique genes (ranked by fold change). (DOC)

Document outlining detailed methodologies. (DOCX)

Significantly enriched gene sets (Gene Ontology Biological Processes, Reactome, KEGG and BioCarta, versions 5.1) using GSEA (FDR<0.05). (XLSX)

Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioural and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively...

A major cause of preterm labor in pregnant women is intra-amniotic infection, which is mediated by an inflammatory process. Hydrogen sulfide (H2S), a gaseous transmitter, has been implicated to be involved in inflammatory responses. We sought to investigate whether H2S affects infectious preterm birth using the mouse model of lipopolysaccharides (L...

Primer sequences used for Realtime PCR. (DOCX)

Injection of NaHS alone didn’t affect the onset of labor. (DOCX)

Introduction: Preterm birth (PTB) is the world's leading cause of perinatal morbidity and mortality. It has been suggested that perinatal programming by stress may increase PTB risk. We have shown that ancestral stress augments PTB risk and is linked with changes in the miR-200 family and targets (Stat5b, Zeb1 and 2) in rat uterus. We propose a two...

Introduction: Preterm birth (PTB) is the world’s leading cause of perinatal morbidity and mortality. It has been suggested that perinatal programming by stress may increase PTB risk. We have shown that ancestral stress augments PTB risk and is linked with changes in the miR-200 family and targets (Stat5b, Zeb1 and 2) in rat uterus. We propose a two...

Introduction: Preterm birth (PTB) is the leading cause of neonatal mortality and morbidity. One of the possible contributors to PTB is chronic maternal stress. We previously conducted a case-control study in Edmonton, AB, Canada, using the Wellbeing and Pregnancy Questionnaire. We showed that adverse childhood experiences (ACEs) in a mother’s life...

INTRODUCTION: Preterm birth (PTB) is the world’s leading cause of neonatal mortality and morbidity. One factor that has been recognized as a contributor to PTB is chronic maternal stress. We previously conducted a retrospective case-¬control study in Edmonton, Canada, in a mainly Caucasian population to evaluate the association between chronic stre...

Preterm birth is a universal health problem that is one of the largest unmet medical needs contributing to the global burden of disease. Adding to its complexity is that there are no means to predict who is at risk when pregnancy begins or when women will actually deliver. Until these problems are addressed, there will be no interventions to reduce...

More than 1 in 10 infants are born prematurely worldwide, making preterm birth the leading cause of neonatal mortality and morbidity. Chronic maternal stress is increasingly recognized as one of the contributing risk factors for preterm birth, yet its specific role remains largely unknown. Examining the exposure to stressors over a mother's life co...

Preterm birth (PTB) is a leading cause of neonatal mortality and morbidity worldwide, and represents a heavy economic and social burden. Despite its broad etiology, PTB has been firmly linked to inflammatory processes. Pro-inflammatory cytokines are produced in gestational tissues in response to stressors and can prematurely induce uterine activati...

Preterm birth (PTB) is firmly linked to inflammation regardless of the presence of infection. Proinflammatory cytokines, including IL-1β, are produced in gestational tissues and can locally upregulate uterine activation proteins. Premature activation of the uterus by inflammation may lead to PTB, and IL-1 has been identified as a key inducer of thi...

An inflammatory response is instrumental in the physiological process of parturition but the upstream signals initiating inflammation are undefined. Since endogenous ligands for Toll-like receptor 4 (TLR4) are released in late gestation, we hypothesised that on-time labor requires TLR4 signaling, to trigger a cytokine and leukocyte response and acc...

IL6 is a determinant of the timing of parturition and birth in mice. We previously demonstrated that genetic IL6 deficiency delays parturition by approximately 24 h, and this is restored by administration of exogenous IL6. In this study, we have investigated whether IL6 influences the number or phenotypes of T cells or other leukocytes in uterine d...

Prostaglandin F2α (PGF2α) plays a critical role in the initiation and process of parturition. Since human labor has been described as an inflammatory event, we investigated the role of PGF2α in the inflammatory process using cultured human uterine smooth muscle cells (HUSMCs) isolated from term pregnant women as a model. Using a multiplex assay, HU...

INTRODUCTION: Every delivery involves inflammatory changes within the uterus. IL-1β and PGF2α are known mediators of this inflammatory response and the uterine transformation into labor. We recently found an increase in mRNA expression of IL-1R1, IL-1R2, IL- 1RAcP and IL-1RAcPb in rat uterus in late gestation. Previously AcPb was found only in brai...

Stress is one of the most powerful experiences to influence health and disease. Through epigenetic mechanisms, stress may generate a footprint that propagates to subsequent generations. Programming by prenatal stress or adverse experience in parents, grandparents, or earlier generations may thus be a critical determinant of lifetime health trajecto...

Canada's perinatal, infant and maternal mortality rates were examined and compared with other Organization for Economic Cooperation and Development (OECD) countries. The type and the quality of the available data and best practices in several OECD countries were evaluated. A literature search was performed in PubMed and the Cochrane Library. Vital...

Problem: Is increased leukocyte chemotactic activity (CA) from gestational tissues necessary for term or preterm labor in guinea pigs? Method of study: Tissue extracts were prepared from pregnant guinea pig decidua-myometrium, cervix, fetal membranes (amniochorion), and placenta during early third trimester (n = 8), term not in labor (TNL, n = 5...

Background Chronic stress is considered to be one of many causes of human preterm birth (PTB), but no direct evidence has yet been provided. Here we show in rats that stress across generations has downstream effects on endocrine, metabolic and behavioural manifestations of PTB possibly via microRNA (miRNA) regulation. Methods Pregnant dams of the...

Each year 15 million babies are born preterm and the global rate of preterm birth (PTB) of >10% is steadily rising. PTB programs life-long complications, including long term motor, cognitive, growth and health problems. A major obstacle in determining the causes of this global problem is that PTB is multifactorial with several different etiologies....

Context: The lower and upper segments of the uterus may play different roles in the process of parturition. The switch from pregnancy to delivery involves changes in expression of uterine activation proteins (UAPs). Prostaglandin (PG) F2α has multiple and complex roles in the birth process in addition to its vital contractile role. Objective: Th...

Preterm birth is the leading cause of mortality and morbidity in newborn infants. Its etiology is multifactorial with genes and environmental factors, including chronic maternal stress, contributing to its risk. Our objective was to investigate whether single nucleotide polymorphisms (SNPs) in genes involved in the stress response are associated wi...

The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal str...

Peripartum events hold the potential to have dramatic effects in the programming of physiology and behaviour of offspring and possibly subsequent generations. Here we have characterized transgenerational changes in rat maternal behaviour as a function of gestational and prenatal stress. Pregnant dams of the parental generation were exposed to stres...

Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine ac...

The development of the in vitro cell culture model has greatly facilitated the ability to study gene expression and regulation within human tissues. Within the human uterus, the upper (fundal) segment and the lower segment may provide distinct functions throughout pregnancy and during labour. We have established primary cultured human myometrial ce...