Bernard Robaire

Reproduction, Pharmacology & Toxicology

Research projects

Impact of the organophosphate ester flame retardants found in the Canadian environment on the reproductive system

Reproductive health is a major concern. Evidence that human fecundity is declining in many geographical regions is reflected by adverse effects on sperm counts and quality, decreased conception rates, and increased time-to-pregnancy. A number of studies have linked adverse reproductive health outcomes to exposure to toxic environmental agents. Exposure to even low, environmentally relevant concentrations of endocrine disrupting chemicals (EDCs) may profoundly affect reproductive health since the endocrine system is essential for normal reproductive function.

Click Here For More Information

Endocrine disrupting chemicals: Towards responsible replacements (website)

As part of our everyday lives we are exposed to a wide variety of chemicals derived from consumer products, such as foam, electronic equipment and plastics, that enter our food and drinking water. Most of these chemicals are present at very low concentrations. However, even low doses of substances that disrupt the body’s own hormones, known as endocrine disrupting compounds (EDCs), can exert important biological effects during critical windows of susceptibility.

Click Here For More Information

Impact of the organophosphate ester flame retardants found in the Canadian environment on the reproductive system - Continued

EDCs that may have an adverse impact on human health are found in many industrial products. The worldwide use of one group of these chemicals, the organophosphate esters (OPEs), has increased >3-fold in the last 15 years. These high production volume chemicals (>10,000 tons/year) are used as flame retardants, plasticizers, solvents, antifoam agents, adhesives and coating for electronic devices. OPEs are detected in air, water and biota globally. Canadian studies suggest that OPEs occur in dust in nearly all of our homes; OPEs and/or their metabolites are detected in the urine of all pregnant and pre-menopausal women. Exposure of cells to environmentally-relevant concentrations affects the production of steroids as well as their signaling mechanisms. There are very limited data from animal studies, but these data suggest that exposure to OPEs causes marked changes in ovarian structure and may influence fertility. The mechanism(s) by which the OPEs cause these effects is (are) unresolved. Essential in vitro and animal studies to identify and characterize the impacts of exposure to environmentally relevant OPE mixtures have not been undertaken. The few human studies that are available indicate that OPE exposure may be correlated with adverse effects on both male and female reproductive health. The need to address these important data gaps is clear.

We hypothesize that OPEs act as EDCs with long term effects on the male and female reproductive systems. We will pursue three specific aims:

Aim 1 is to investigate the molecular mechanism(s) underlying the effects of OPEs using an in vitro approach. Cells with key endocrine functions will be used to identify genes and pathways that are disrupted by OPEs and may serve as biomarkers of their effects on fertility.

Aim 2 is to elucidate the effects of exposure to the mixture of OPEs found in Canadian house dust on male and female fertility in an animal model.

Aim 3 is to assess the association of human OPE body burden with female and male infertility. Biological samples collected from individuals attending infertility clinics in Montreal will be analyzed for OPEs and their metabolite levels using validated methods and the association with fertility will be assessed.

Together, we have extensive expertise with determining how xenobiotics act on the male and female reproductive system, with hazard assessment and with knowledge transfer. We have a history of successful collaborations. These studies will enhance our understanding of the mechanisms underlying the adverse effects of OPEs and the consequences of exposure to these chemicals on the reproductive system, both in animal models and in humans.


Impact of Paternal Age on the Health of Gametes: Risk of Potential Adverse Outcomes - Continued

The objective of this study is to examine how the trajectory of aging presents health challenges faced not only for older men but also for their children. Men older than 40 years of age take a longer time to make their partner pregnant and have a higher rate of infertility; partners of these men have a higher incidence of miscarriage.

Paternal age is also linked to a higher risk for progeny to develop complex multi-gene diseases, such as autism, schizophrenia, and bipolar disease. Since sperm continue to be produced in men constantly throughout adult life at a rate of about 1000 sperm every heartbeat, decreased sperm cell function is likely to be associated with decreased sperm quality and not number.

The central hypothesis underlying this Team Grant is that the trajectory of aging alters the quality of the sperm being delivered to the oocyte and that there is a direct relationship between infertility, paternal age, chromatin quality, epigenetic marks, and progeny outcome.

Our studies represent a unique approach. There has been little attention to the quality of men's sperm as men move along their aging trajectory. The consequences of increased paternal age are only beginning to be demonstrated in studies from other countries. Our team has gathered the essential complementary expertise to make significant advances in this field.

Our results will not only have positive consequences for men as they appreciate the link between aging and sperm chromatin quality but will also serve to decrease the health burden on future generations.


EDCs - Continued

In the past decade governments across the world have regulated the production, uses and importation of specific flame retardants, plasticizers, and food packaging materials that have been shown to act as endocrine disruptors. The consequence is that alternative chemicals are needed to fill market “gaps”. However, there is often little information on the degree to which we are exposed to these replacements or on their health impacts.

Our research will focus first on determining the extent to which our food, drinking water and breast milk contain the chemicals that have emerged as replacements for polybrominated diphenyl ether flame retardants, phthalates and bisphenol A. We will then determine if these new alternatives are safer than the substances that they have replaced. We will investigate the effectiveness of various food preparation procedures and water purification strategies to decrease exposure and thus prevent possible adverse health effects associated with alternatives that are deemed to be hazardous. Finally, we will analyze international regulations and regulatory processes related to the assessment of alternatives, with a focus on Canada, US, Europe and South Africa.

Our goal is to transform the knowledge that is acquired during this team grant into international policy objectives and legal standards.