In utero and lactational PCB exposure drives anatomic changes in the juvenile mouse bladder

Abstract

Graphical abstract

Genome-Wide DNA Methylation Profiles of Neurodevelopmental Disorder Genes in Mouse Placenta and Fetal Brain Following Prenatal Exposure to Polychlorinated Biphenyls

“…The PCB mixture consisted of the following non-dioxin like congeners in differing proportions: PCB 28 (48.2%), PCB 11 (24.3%), PCB 118 (4.9%), PCB 101 (4.5%), PCB 52 (4.5%), PCB 153 (3.1%), PCB 180 (2.8%), PCB 149 (2.1%), PCB 138 (1.7%), PCB 84 (1.5%), PCB 135 (1.3%) and PCB 95 (1.2%). C57BL/6J dams (The Jackson Laboratory, 000664) aged 6 to 8 weeks were orally exposed to 1.0 mg/kg/d of the PCB mixture through diet (peanut butter) or vehicle (peanut oil in peanut butter) for at least 2 weeks before conception and during pregnancy, as previously described (Keil Stietz et al 2021). Pregnant dams were euthanized on gestational day 18 and whole brain and placenta were dissected from 44 fetuses and flash frozen.…”

The Bladder Is a Novel Target of Developmental Polychlorinated Biphenyl Exposure Linked to Increased Inflammatory Cells in the Bladder of Young Mice

“…We have previously described the MARBLES PCB mixture and doses selected, 0.1, 1 and 6 mg/kg body weight/day, which result in PCB levels in offspring tissues within ranges observed in humans and do not interfere with reproductive outcomes of the dam [ 32 , 45 , 46 ]. The proportion of individual PCB congeners in the MARBLES PCB mixture mimics the proportion of the top 12 PCB congeners identified in pregnant women at risk of having a child with a neurodevelopmental disorder [ 18 , 28 , 31 ].…”

“…All procedures involving animals were conducted in accordance with the NIH Guide for the Care and Use of Laboratory Animals and were approved by the University of California-Davis Animal Care and Use Committee (#18853 and 20584; date of approval: 8-5-15 and 8-3-18 respectively). Wild-type mice of 75% C57BL/6J/25% SVJ129 genetic background (Jackson Labs, Sacramento, CA, USA), were used in this study and were collected as part of a larger study as described previously [32,45]. All mice were housed in clear plastic cages containing corn cob bedding and maintained on a 12 h light and dark cycle at 22 ± 2 • C. Feed (Diet 5058, LabDiet, St. Louis, MO, USA) and water were available ad libitum.…”

“…Here, we use the Markers of Autism Risk in Babies Learning Early Signs (MARBLES) PCB mixture which mimics the proportion of the top PCB congeners detected in the serum of women at risk of having a child with a neurodevelopmental disorder [ 28 , 31 ]. This mixture not only replicates an environmentally relevant mixture found in the human population, but also consists of legacy higher-chlorinated PCBs in addition to contemporary lower chlorinated PCBs such as PCB 11 [ 28 , 32 ].…”

“…To expand upon the evidence that PCBs can increase serum cytokine in juvenile mice following developmental exposure, we sought to determine whether PCBs alter inflammation in other organs of interest such as the bladder. We focus on the bladder as we have previously shown that PCBs are not only detected in mouse bladder following developmental exposure, but that PCBs lead to changes in neuromorphology which are correlated with increased mast cell numbers [ 32 ]. Here, we test the hypothesis that developmental exposure to the environmentally relevant MARBLES PCB mixture results in increased immune cells within the bladder of juvenile male and female mice and test whether these cells are associated with changes to the extracellular matrix collagen density.…”