Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury.
Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2024-01-01
|
| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301824&type=printable |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849240157796958208 |
|---|---|
| author | Kapish Gupta Jimmy P Xu Tamir Diamond Iris E M de Jong Andrew Glass Jessica Llewellyn Neil D Theise Orith Waisbourd-Zinman Jeffrey D Winkler Edward M Behrens Clementina Mesaros Rebecca G Wells |
| author_facet | Kapish Gupta Jimmy P Xu Tamir Diamond Iris E M de Jong Andrew Glass Jessica Llewellyn Neil D Theise Orith Waisbourd-Zinman Jeffrey D Winkler Edward M Behrens Clementina Mesaros Rebecca G Wells |
| author_sort | Kapish Gupta |
| collection | DOAJ |
| description | Biliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury. |
| format | Article |
| id | doaj-art-74507efcbeca4a1daf62e83fff6e33fb |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-74507efcbeca4a1daf62e83fff6e33fb2025-08-20T04:00:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01194e030182410.1371/journal.pone.0301824Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury.Kapish GuptaJimmy P XuTamir DiamondIris E M de JongAndrew GlassJessica LlewellynNeil D TheiseOrith Waisbourd-ZinmanJeffrey D WinklerEdward M BehrensClementina MesarosRebecca G WellsBiliary atresia is a neonatal disease characterized by damage, inflammation, and fibrosis of the liver and bile ducts and by abnormal bile metabolism. It likely results from a prenatal environmental exposure that spares the mother and affects the fetus. Our aim was to develop a model of fetal injury by exposing pregnant mice to low-dose biliatresone, a plant toxin implicated in biliary atresia in livestock, and then to determine whether there was a hepatobiliary phenotype in their pups. Pregnant mice were treated orally with 15 mg/kg/d biliatresone for 2 days. Histology of the liver and bile ducts, serum bile acids, and liver immune cells of pups from treated mothers were analyzed at P5 and P21. Pups had no evidence of histological liver or bile duct injury or fibrosis at either timepoint. In addition, growth was normal. However, serum levels of glycocholic acid were elevated at P5, suggesting altered bile metabolism, and the serum bile acid profile became increasingly abnormal through P21, with enhanced glycine conjugation of bile acids. There was also immune cell activation observed in the liver at P21. These results suggest that prenatal exposure to low doses of an environmental toxin can cause subclinical disease including liver inflammation and aberrant bile metabolism even in the absence of histological changes. This finding suggests a wide potential spectrum of disease after fetal biliary injury.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301824&type=printable |
| spellingShingle | Kapish Gupta Jimmy P Xu Tamir Diamond Iris E M de Jong Andrew Glass Jessica Llewellyn Neil D Theise Orith Waisbourd-Zinman Jeffrey D Winkler Edward M Behrens Clementina Mesaros Rebecca G Wells Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. PLoS ONE |
| title | Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. |
| title_full | Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. |
| title_fullStr | Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. |
| title_full_unstemmed | Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. |
| title_short | Low-dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring: Evidence for a spectrum of neonatal injury. |
| title_sort | low dose biliatresone treatment of pregnant mice causes subclinical biliary disease in their offspring evidence for a spectrum of neonatal injury |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0301824&type=printable |
| work_keys_str_mv | AT kapishgupta lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT jimmypxu lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT tamirdiamond lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT irisemdejong lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT andrewglass lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT jessicallewellyn lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT neildtheise lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT orithwaisbourdzinman lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT jeffreydwinkler lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT edwardmbehrens lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT clementinamesaros lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury AT rebeccagwells lowdosebiliatresonetreatmentofpregnantmicecausessubclinicalbiliarydiseaseintheiroffspringevidenceforaspectrumofneonatalinjury |