Warren Foster

• Ph.D., FCAHS
• Professor (Full) at Michael G. DeGroote School of Medicine & McMaster University

Background Few high-quality studies have evaluated associations between urinary glyphosate or its environmental degradate (aminomethylphosphonic acid (AMPA)] and preterm birth (PTB). Objectives To quantify associations between urinary glyphosate and AMPA and preterm birth in the pan-Canadian Maternal-Infant Research on Environmental Chemicals (MIR...

Objective To study the association between maternal exposure to arsenic, cadmium, lead, manganese and mercury, time‐to‐pregnancy (TTP) and infertility. Design Pregnancy‐based retrospective TTP cohort study. Setting Hospitals and clinics from ten cities across Canada. Population A total of 1784 pregnant women. Methods Concentrations of arsenic,...

Phthalates are non-persistent chemicals measured as metabolites in urine. Over time, new metabolites have been identified. In the original Maternal-Infant Research on Environmental Chemicals (MIREC) study (2008-2011), we measured 11 phthalate metabolites in first trimester urine samples. The goal of the present study was to develop a method to meas...

Background: Toxic metals, such as lead (Pb), cadmium (Cd), arsenic (As), and mercury (Hg), may be associated with a higher risk of gestational hypertension and preeclampsia, whereas manganese (Mn) is an essential metal that may be protective. Objectives: We estimated the individual, independent, and joint associations of Pb, Cd, As, Hg, and Mn o...

Problem: Estrogen-dependent extrauterine implantation and growth of menstrual endometrial tissue affects roughly 10% of reproductive age women and depends on suppression of local innate immune defenses to prevent ectopic tissue rejection. Immunohistochemistry has shown the immune check-point inhibitor CD200 which can suppress rejection is expresse...

Background Glyphosate is the most widely applied herbicide in agriculture. Glufosinate is a broad spectrum herbicide used to manage glyphosate-resistant weeds. Despite the widespread use of these herbicides, biomonitoring data – which inform risk assessment and management – are sparse. Objectives To identify determinants of urinary concentrations...

Objectives To describe the use and perceived effectiveness of medical, surgical, and alternative therapies (e.g. diet, exercise, heat, cannabis, etc.) in managing endometriosis-associated pain in Canadians. Methods A cross-sectional online survey was distributed via The Endometriosis Network Canada (TENC) from February to March 2021. Canadians 18-...

Endometriosis and adenomyosis are estrogen dependent disorders and hence, one of the major pillars in their medical management has been to suppress circulating estrogen levels. Given that the primary source of premenopausal endogenous estrogen is estradiol production from the ovaries, the principal mechanism for estrogen suppression has been throug...

PurposeInduction of labour has become more common over the last decade, together with an increase in the number of systematic reviews of the subject. However, with multiple systematic reviews it is necessary to evaluate the methodological rigor to ensure the reliability of conclusions and recommendations for clinical practice. Therefore, the aim of...

Endometriosis is a chronic, estrogen-dependent gynecological condition affecting approximately 10% of reproductive age women. The most widely accepted theory of its etiology includes retrograde menstruation. Recent reports suggest the uterus is not sterile. Thus, the refluxed menstrual effluent may carry bacteria, and contribute to inflammation, th...

Background: Bisphenol A (BPA) is typically measured in urine using an indirect method that involves enzymatic deconjugation and extraction. In contrast, the direct method measures free and conjugated BPA concurrently and sums them to estimate urinary BPA concentrations. Statistical comparison of total BPA results using the direct and indirect meth...

Endometriosis is a common gynaecological condition characterized by estrogen dependence, chronic pelvic pain, infertility and diagnostic delay of between 5.4 and 12 years. Despite extensive study, no biomarker, either alone or in combination with other markers, has proven superior to laparoscopy for the diagnosis of endometriosis. Recent studies re...

lncRNA, miRNA, and proteins in exosomes isolated from the serum and peritoneal fluid of women with endometriosis are differentially expressed compared to controls. Experimental evidence demonstrates that exosome content modulates migration, invasion, angiogenesis and inflammation, central processes in endometriosis. We suggest that exosomes and the...

Childhood exposure to phthalates, a class of chemicals with known reproductive and developmental effects, has been hypothesized to increase the risk of obesity, but this association is not well understood in preschool children. We examined the association between urinary concentrations of phthalate metabolites and concurrently measured body mass in...

Abstract Background Women with endometriosis are commonly treated by their sole provider. In this single-provider model of care, women frequently report long diagnostic delays, unresolved pelvic pain, multiple laparoscopic surgeries, sequential consultations with numerous providers, and an overall dissatisfaction with care. The emergence of multidi...

Background Postpartum depression (PPD) is a highly prevalent mental health problem that affects parental health with implications for child health in infancy, childhood, adolescence and beyond. The primary aim of this study was to critically appraise available systematic reviews describing interventions for PPD. The secondary aim was to evaluate th...

Circulating concentrations of brain-derived neurotrophic factor (BDNF) have been linked to cancer, neuropsychiatric, diabetes, and gynecological disorders. However, factors influencing plasma storage and subsequent BDNF quantification are incompletely understood. Therefore, the anticoagulant used in plasma separator tubes, storage-time, storage-tem...

Objective To identify novel candidate diagnostic microRNA (miRNA) markers of endometriosis by means of an unbiased search with confirmation by means of targeted polymerase chain reaction (PCR). Design Retrospective cohort. Setting University teaching hospitals. Patient(s) Women with endometriosis and control women, confirmed with the use of lapa...

Background: Neurotrophins of the nerve growth factor family are soluble polypeptides that are best known for their role in nerve growth, survival and differentiation in the central nervous system. A growing body of literature shows that neurotrophins and their receptors are also expressed throughout the reproductive tract. Objective and rationale...

Background Synthetic musk compounds are widely used as fragrances in many consumer products; however, information on human exposure and health effects is limited. Also, analytical methods for their quantification in biological matrices are limited. Objective In this study, an integrated method was developed and validated for the analysis of select...

Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants...

Exposure to the man-made chemicals perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorohexanesulfonate (PFHxS) is widespread. These perfluoroalkyl substances (PFASs) have been associated with androgenic endocrine-disrupting properties; however, the evidence is equivocal and few human studies have examined the association be...

Endometriosis is a common estrogen dependent and inflammatory disease affecting approximately 176 million women worldwide. Currently, the time between onset of symptoms and a definitive diagnosis has been reported by several international studies to range from 6 to 12 years. Presently, laparoscopic surgery followed by histopathological confirmation...

The uterine environment in which a foetus develops is critical to infant, child, and adult health. Adverse intra-uterine environments have been linked to increased risk for neurobehavioral disorders and metabolic and cardiovascular disease. Rapid cell division, tissue growth, differentiation, and organization of major organs are all features render...

Fetal exposure to some toxic metals has been associated with reduced fetal growth, but the impact of contemporary, low-level metals on anthropometric measures in childhood is not well understood. Our primary objective was to quantify associations between childhood levels of toxic metals and concurrently measured body mass index (BMI) in a populatio...

Endometriosis is a chronic, painful disease without a cure. Due largely to chronic pain, endometriosis can lead to significant physical, mental, relationship, and financial burdens. Within the conventional single provider model of care—in which the patient is primarily taken care of by her physician and complementary strategies based on psychology,...

Anogenital distance (AGD) has been used as a marker of fetal androgen action to identify endocrine disrupting chemicals. A US study (TIDES) has reported that the association between some phthalates and reduced AGD in males was only apparent in sons of mothers reporting no stressful life events (SLEs) during pregnancy. The objective of the current s...

Study question: Are melatonin receptors (melatonin receptor 1A (MR1A) and melatonin receptor 1B (MR1B)) expressed in human endometrium and endometriotic tissue, and does melatonin affect endometrial cell proliferation? Summary answer: Melatonin receptors are expressed in human eutopic endometrium, endometriomas and peritoneal lesions, although t...

Objectives To investigate the expression of melatonin receptors (MR1A and MR1B) in human endometrium and endometriotic tissues. Methods Study participants included women (n=31) with a confirmed diagnosis of endometriosis (endometrioma n=20 and peritoneal lesions n=11). The control group were women with pelvic pain but no evidence of endometriosis...

While adult exposure to total bisphenol A (BPA) has been well documented, developmental exposure to BPA and fetal exposure to the bioactive form (free BPA) remains poorly defined. Therefore, pregnant women (n = 199) between 28 and 35 weeks of pregnancy were invited to participate in this study. Maternal serum free of hemolysis (n = 189) and urine (...

Background: Anogenital distance (AGD) and the second to fourth finger (2D:4D) digit ratio may be early markers of in utero androgen exposure for the infant. Phthalates and phenols have been identified as endocrine disrupting chemicals. Objectives: To study the association between prenatal exposure to phthalates, bisphenol A (BPA) and triclosan (...

MicroRNA (miRNA), non-coding segments of RNA involved in post-transcriptional regulation of protein expression, are differentially expressed in eutopic endometrium of women with and without endometriosis compared to endometriotic lesions. However, endometriotic lesion types are known to be biochemically distinct and therefore hypothesized that miRN...

Exposure to environmental toxicants has been associated with ovarian dysfunction yet sensitive biomarkers of adverse effect are lacking. We previously demonstrated that cigarette smoke exposure induced decreased relative ovarian weight, increased follicle loss and granulosa cell autophagy in mice. We postulate that cigarette smoke exposure will ind...

Herbals and supplements are frequently sold over the counter without the requirement of a prescription. While the beneficial effects are widely promoted in the lay press, the impact of these compounds on health may be positive, negative, or neutral. This chapter focuses on the effects of exogenous chemicals on the reproductive system across the lif...

Many people are repeatedly exposed to both bisphenol A (BPA) and diethylhexyl phthalate (DEHP), but there has been little research concerning their effects in combination. Both can disrupt blastocyst implantation in inseminated females, albeit at high doses. We exposed mice on gestation days (GD) 1–4 to combinations of BPA and DEHP in doses below t...

A rapid mass spectrometric method was applied to non-targeted screening of DNA adducts in follicular cells (granulosa cells and theca cells) from isolated ovarian follicles that were exposed in-vitro to benzo[a]pyrene (B[a]P) and cigarette smoke condensate (CSC) for 13 days of culture. The method employed a constant neutral loss (CNL) scan to ident...

Congenital anomalies are an important cause of infant mortality and disability. Developmental exposure to environmental contaminants is thought to increase the risk for congenital anomalies. Herein, we describe a critical review of the literature conducted between February and March 2014 yielding 3057 references from which 97 unique relevant articl...

Parabens are hormonally active chemicals widely used as preservatives in foods and are frequently detected in human fluids and tissues. Therefore, the objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on male sexual development. Pregnant Wistar rats received corn oil (control group), or BP at doses of 10,...

Purpose: The aim was to validate a food frequency questionnaire (FFQ) against a 3-day food record (3DFR) for pregnant women with a focus on nutrients important for bone health from food and supplements. Methods: The FFQ and 3DFR were administered to pregnant women (n = 42) aged 18-45 years in their third trimester of pregnancy in Hamilton, Ontar...

Background Pregnant women are an especially important population to monitor for environmental exposures given the vulnerability of the developing fetus. During pregnancy and lactation chemical body burdens may change due to the significant physiological changes that occur. Developmental exposures to some persistent organic pollutants (POPs) have be...

Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) (ranging from 10(-9) to 10(-7) m [1-100 nm; 0.39-39 ng ml(-1) ]) and butylparaben (BP) (ranging from 10(-8) to 10(-5...

Exposure to environmental contaminants is thought to be important in the development of adverse effects on reproductive health. While the adverse effects of environmental contaminants on semen quality and testicular function have been well studied, effects on ovarian function are less well defined. Epidemiological studies have linked exposure to en...

Parabens and phthalates are commercial chemicals widely used in the manufacture of industrial and consumer products frequently found as contaminants in biological fluids. We evaluated the effects of di-(2-ethylhexyl) phthalate (DEHP) (ranging from 10 –9 to 10 –7 M [1–100 nM; 0.39–39 ng ml –1 ]) and butylparaben (BP) (ranging from 10 –8 to 10 –5 M [...

We previously demonstrated that Cigarette Smoke (CS) induces autophagy in the ovary. Therefore we aimed to determine if chloroquine (CQ) could inhibit CS-induced autophagy in the ovary. Eight week old mice were implanted with CQ pellets; 0, 25, and 50mg CQ/Kg. Half of the animals in each group were exposed to room air and the other half were expose...

Over the last few years, the use of organophosphate flame retardants (OPFRs) has been on the rise; however, there are knowledge gaps in both the human health effects of OPFRs and levels of human exposure. Currently, human biomonitoring data on the levels of OPFR metabolites in the Canadian population are still non-existent. Herein we describe a nov...

The Health and Environmental Sciences Institute (HESI) Developmental and Reproductive Toxicology Technical Committee sponsored a pharmaceutical industry survey on current industry practices for contraception use during clinical trials. The objectives of the survey were to improve our understanding of the current industry practices for contraception...

Objective: To evaluate novel clinical markers of endometriosis including the neurotrophins brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and neurotrophin 4/5 (NT4/5) and compare them to others previously reported in the literature including cancer antigen 125 (CA-125) and C-reactive protein (CRP). Design: Prospective study...

We previously demonstrated that cigarette smoke (CS) exposure decreases primordial follicle counts and induces autophagy in ovarian granulosa cells in preference to apoptosis. Therefore, the objective of this study was to investigate molecular targets underlying smoke-induced activation of the reparative autophagy pathway in the ovary. Briefly, ova...

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The purpose of this study was to assess the impact of 3 months of aromatase inhibition together with progestin add-back on ovarian endometrioma size. This prospective cohort study was performed at University Medical Center (UC San Diego). Women trying to conceive were excluded. After informed consent, all women were treated with the aromatase inhib...

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In addition to estrogen dependence, endometriosis is characterized by chronic pelvic inflammation. The impact of the chronic pelvic inflammatory state on other organ systems and women’s health is unclear. Endometriosis associated chronic inflammation and potential adverse health effects across the lifespan render it imperative for renewed research...

Background The aim of this study was to systematically review the impact of surgical excision of deep infiltrating endometriosis involving the bowel, on health-related quality of life, based on the currently available literature. Methods A systematic review was completed of English-language publications in the last 10 years, which had assessed the...

Impact of surgical excision of deep infiltrating bowel endometriosis on health-related quality of life: review of current literature Kristina Arendas, Warren G. Foster, Nicholas A. Leyland Journal of Endometriosis and Pelvic Pain Disorders Jan-Mar 2015 Vol. 7 Issue 1 pp. 1-50

Are brain-derived neurotrophic factor (BDNF) and its receptors, NTRK2, NGFR and SORT1, regulated by ovarian steroids in the uterus? BDNF and its low affinity receptor, nerve growth factor receptor (NGFR), are regulated by estradiol in the uterus. Recent studies have revealed a central role for neurotrophins in placental development, endometrial ste...

. This randomized, multicenter, open-label clinical trial was intended to generate pilot data on the efficacy and safety of the gonadotropin-releasing hormone agonist (GnRHa) deslorelin (D) with low-dose estradiol ± testosterone (E 2 ± T) add-back for endometriosis-related pelvic pain. Methods . Women with pelvic pain and laparoscopically confirmed...

Under the North American Commission for Environmental Cooperation (CEC) and its Sound Management of Chemicals (SMOC) program, a tri-national human contaminant monitoring initiative was completed to provide baseline exposure information for several environmental contaminants in Canada, Mexico and the United States (U.S). Blood samples were collected...

Lipophilic persistent environmental chemicals (LPECs) have the potential to accumulate within a woman's body lipids over the course of many years prior to pregnancy, to partition into human milk, and to transfer to infants upon breastfeeding. As a result of this accumulation and partitioning, a breastfeeding infant's intake of these LPECs may be mu...

Bisphenol A (BPA) and phthalates are endocrine disruptors possibly linked to adverse reproductive and neurodevelopmental outcomes. These chemicals have commonly been measured in urine in population surveys; however, such data are limited for large populations of pregnant women, especially for the critical first trimester of pregnancy. The aim of th...

Phthalate diesters are a diverse group of chemicals used to make plastics flexible and are found in personal care products, medical equipment, and medication capsules. Ubiquitous in the environment, human exposure to phthalates is unavoidable; however, the clinical relevance of low concentrations in human tissues remains uncertain. The epidemiologi...

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been...

Early in 2013, the World Health Organization (WHO) released a 2012 update to the 2002 State of the Science of Endocrine Disrupting Chemicals. Several significant concerns have been identified that raise questions about conclusions reached in this report regarding endocrine disruption. First, the report is not a state-of-the-science review and does...

Bisphenol A (BPA) is a widely used industrial chemical in the manufacturing of polycarbonate plastic bottles, food and beverage can linings, thermal receipts, and dental sealants. Animal and human studies suggest that BPA may disrupt normal hormonal function and hence, potentially, have negative effects on the human health. While total BPA is frequ...

The exposure of Aboriginal peoples in the Canadian Arctic to persistent organic pollutants (POPs) and metals through the consumption of traditional food items is well recognized; however, less information is available for Canadian immigrants. The direct comparison of blood chemical concentrations for expectant primiparous women sampled in the Inuvi...

The neurotrophins are neuropeptides that are potent regulators of neurite growth and survival. Although mainly studied in the brain and nervous system, recent reports have shown that neurotrophins are expressed in multiple target tissues and cell types throughout the body. Additionally, dysregulation of neurotrophins has been linked to several dise...

Bisphenol A (BPA) and phthalates are endocrine disruptors possibly linked to adverse reproductive and neurodevelopmental outcomes. These chemicals have commonly been measured in urine in population surveys; however, such data are limited for large populations of pregnant women, especially for the critical first trimester of pregnancy. The aim of th...

Numerous biochemical differences have been documented in women with endometriosis compared to controls; however, identification of a clinically useful marker of endometriosis remains elusive. We postulate that the diversity of clinical presentations, patient objectives, and complexity of the pathophysiology of endometriosis mandates rigorous attent...

This study assessed the influence of cigarette smoke condensate (CSC) and benzo(a)pyrene [B(a)P] on the levels of two oxidative stress biomarkers [8-isoprostane (8-IsoP) and 8-hydroxy-2-deoxy Guanosine (8-OH-dG)], in in-vitro spent media of follicle cells. Follicles (100-130 µm) isolated from ovaries of F1 hybrid (C57Bl/6j × CBA/Ca) mice were cultu...

Fertility and Sterility Volume 100, Issue 3, Supplement , Pages S101-S102, September 2013 Can brain-derived neurotrophic factor be a clinical marker for endometriosis? J.M. Wessels , N.A. Leyland , S. Agarwal , A. Murji , W.G. Foster

The Maternal-Infant Research on Environmental Chemicals (MIREC) Study was established to obtain Canadian biomonitoring data for pregnant women and their infants, and to examine potential adverse health effects of prenatal exposure to priority environmental chemicals on pregnancy and infant health. Women were recruited during the first trimester fro...

Benzo[a]pyrene (B[a]P) is a prototypical polycyclic aromatic hydrocarbon (PAH) present in cigarette smoke. We previously showed that B[a]P adversely affects follicular development and survival. The objective of this study was to identify the key molecular pathways underlying B[a]P-induced abnormal follicular development. Isolated follicles (100-130...