TY - JOUR
T1 - PCB126 exposure during pregnancy alters maternal and fetal gene expression
AU - Rashid, Cetewayo S.
AU - Preston, Joshua D.
AU - Ngo Tenlep, Sara Y.
AU - Cook, Marissa K.
AU - Blalock, Eric M.
AU - Zhou, Changcheng
AU - Swanson, Hollie I.
AU - Pearson, Kevin J.
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/8
Y1 - 2023/8
N2 - Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)-regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 µmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of cytochrome P450 (Cyp)1a1 and Cyp1b1 were significantly increased in response to PCB exposure in the tested maternal and fetal tissues. Furthermore, PCB exposure altered the expression of several other genes related to energy balance, oxidative stress, and epigenetic regulation in a manner that was less consistent across tissue types. These results indicate that maternal PCB126 exposure significantly alters gene expression in both developing fetuses and pregnant dams, and such changes vary in intensity and expressivity depending on tissue type. The altered gene expression may provide insights into pathophysiological mechanisms by which in utero PCB exposures contribute to PCB-induced postnatal metabolic diseases.
AB - Polychlorinated biphenyls (PCBs) are organic pollutants that can have lasting impacts on offspring health. Here, we sought to examine maternal and fetal gene expression differences of aryl hydrocarbon receptor (AHR)-regulated genes in a mouse model of prenatal PCB126 exposure. Female mice were bred and gavaged with 1 µmole/kg bodyweight PCB126 or vehicle control on embryonic days 0 and 14, and maternal and fetal tissues were collected on embryonic day 18.5. Total RNAs were isolated, and gene expression levels were analyzed in both maternal and fetal tissues using the NanoString nCounter system. Interestingly, we found that the expression levels of cytochrome P450 (Cyp)1a1 and Cyp1b1 were significantly increased in response to PCB exposure in the tested maternal and fetal tissues. Furthermore, PCB exposure altered the expression of several other genes related to energy balance, oxidative stress, and epigenetic regulation in a manner that was less consistent across tissue types. These results indicate that maternal PCB126 exposure significantly alters gene expression in both developing fetuses and pregnant dams, and such changes vary in intensity and expressivity depending on tissue type. The altered gene expression may provide insights into pathophysiological mechanisms by which in utero PCB exposures contribute to PCB-induced postnatal metabolic diseases.
KW - Aryl Hydrocarbon Receptor
KW - Cytochrome P450
KW - Developmental Toxicity
KW - Endocrine-Disrupting Chemicals
KW - Polychlorinated Biphenyls, Persistent Organic Pollutants
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U2 - 10.1016/j.reprotox.2023.108385
DO - 10.1016/j.reprotox.2023.108385
M3 - Article
C2 - 37080397
AN - SCOPUS:85158065479
SN - 0890-6238
VL - 119
JO - Reproductive Toxicology
JF - Reproductive Toxicology
M1 - 108385
ER -