Perinatal Exposure to Environmental Contaminants Detected in Canadian Arctic Human Populations Changes Bone Geometry and Biomechanical Properties in Rat Offspring

Abstract

Arctic inhabitants consume large proportions of fish and marine mammals, and are therefore continuously exposed to levels of environmental toxicants, which may produce adverse health effects. Fetuses and newborns are the most vulnerable groups. The aim of this study was to evaluate changes in bone geometry, mineral density, and biomechanical properties during development following perinatal exposure to a mixture of environmental contaminants corresponding to maternal blood levels in Canadian Arctic human populations. Sprague-Dawley rat dams were dosed with a Northern Contaminant Mixture (NCM) from gestational day 1 to postnatal day (PND) 23. NCM contains 27 contaminants comprising polychlorinated biphenyls, organochlorine pesticides, and methylmercury. Femurs were collected on PND 35, 77 and 350, and diaphysis was analyzed by peripheral quantitative computed tomography and three-point bending test, while femoral neck was assessed in an axial loading experiment. Dose-response modeling was performed to establish the benchmark dose (BMD) for the analyzed bone parameters. Exposure to the high dose of NMC resulted in short and thin femur with reduced mechanical strength in offspring at PND35. BMD of femur length, cortical area, and stiffness were 3.2, 1.6, and 0.8 mg/kg bw/d, respectively. At PND77 femur was still thin, but at PND350 no treatment-related bone differences were detected. This study provides new insights on environmental contaminants present in the maternal blood of Canadian Arctic populations, showing that perinatal exposure induces bone alterations in the young offspring. These findings could be significant from a health risk assessment point of view.

Alterations in geometry, biomechanics, and mineral composition of juvenile rat femur induced by nonplanar PCB‐155 and/or planar PCB‐169

“…Decreased femur length and cross‐sectional geometry parameters (CSA and perimeters) were observed in developing and adult rats that were exposed to TCDD (Finnilä et al, ; Miettinen et al, ); however, the bone growth impairment was reversible after elimination of TCDD from the body (Miettinen et al, ). Similarly, rat offspring exposed in utero and lactationally to either A1254 (Elabbas et al, ) or a contaminant mixture composed of 14 PCB congeners (Elabbas et al, ) had decreased femur and tibia lengths (Elabbas et al, ) and decreased total and cortical cross‐sectional areas and perimeters on PND 35; these effects disappeared by PND 77 and PND 350 (Elabbas et al, ). The smaller medullary area of the femur mid‐diaphysis in the PCB‐169 group is in accordance with data obtained in adult animals chronically exposed to TCDD (Herlin et al, ; Jämsä et al, ); a relatively small medullary area was also suggested be a sensitive and consistently affected endpoint of AhR‐mediated toxicity (Herlin et al, ; Jämsä et al, ).…”

“…Transfer of PCB congeners to mature and developing bone tissue has previously been documented (Jan et al, ; Jan et al, ), and accumulating evidence has demonstrated their ability to modulate bone morphology, development and bone mineral density (Andrews, ; Lind et al, ; Cocchi et al, ; Sonne et al, ). In laboratory rats, alterations in growth and bone tissue homeostasis have been well documented after short‐term or chronic exposure to mixtures of environmental contaminants (Elabbas et al, ), dioxins (Jämsä et al, ; Lind et al, ; Nishimura et al, ) and PCBs (Lind et al, ; Ramajayam et al, ). More specifically, in utero and lactational TCDD exposure affected the bone growth and mechanical strength of wild‐type AhR rats but not dioxin‐resistant rats (Miettinen et al, ; Nishimura et al, ).…”

Canadian Arctic Contaminants and Their Effects on the Maternal Brain and Behaviour: A Scoping Review of the Animal Literature

“…Many researchers have explored the impact of the abovementioned pollutants on the neurological health of offspring [52][53][54][55]. Considering the sensitive period of in utero development, studies have focused on developmental outcomes following toxicant exposure.…”

Lactational exposure to dioxin-like polychlorinated biphenyl 169 and nondioxin-like polychlorinated biphenyl 155: Effects on rat femur growth, biomechanics and mineral composition

“…Exposure to PCBs and environmental organochlorines has been shown to affect bone mineral density in humans (Hodgson et al, 2008) and wild animals including polar bears (Daugaard-Petersen; Sonne et al, 2015), Baltic grey seal (Lind et al, 2003) and freshwater turtle (Ming-Ch'eng Adams et al, 2016). Bone studies in experimental animals reported biochemical and toxicological responses after exposure to TCDD (Herlin et al, 2013;Jämsä et al, 2001;Lind et al, 2009;Nishimura et al, 2009), environmental and commercial mixtures of chemical pollutants (Daugaard-Petersen et al, 2018;Elabbas et al, 2011aElabbas et al, , 2011bRamajayam et al, 2007) or individual PCBs (Brankovič et al, 2017;Gutleb et al, 2010;Lind et al, 2000). In young animals, after in utero and lactational exposure to TCDD, bone growth and mechanical strength were affected in wild-type AhR rats on postnatal day (PND) 40 (Miettinen et al, 2005), and bone mineralization was impaired in mice on PND 21 (Nishimura et al, 2009).…”