PMID- 33126512 OWN - NLM STAT- MEDLINE DCOM- 20210122 LR - 20220910 IS - 1660-4601 (Electronic) IS - 1661-7827 (Print) IS - 1660-4601 (Linking) VI - 17 IP - 21 DP - 2020 Oct 28 TI - Prenatal Exposure to Gutkha, a Globally Relevant Smokeless Tobacco Product, Induces Hepatic Changes in Adult Mice. LID - 10.3390/ijerph17217895 [doi] LID - 7895 AB - Maternal exposures during pregnancy affect the onset and progression of adult diseases in the offspring. A prior mouse study indicated that maternal tobacco smoke exposure affects hepatic fibrosis in adult offspring. Gutkha, a broadly used smokeless tobacco (ST) product, is widely used by pregnant woman in many countries. The objective of this murine study was to evaluate whether oral maternal exposure to gutkha during pregnancy alters non-alcoholic fatty liver disease (NAFLD) in adult offspring: risk factors for the progression of NAFLD to cirrhosis in adults remain elusive. Buccal cavity 'painting' of pregnant mice with gutkha began on gestational days (GD) 2-4 and continued until parturition. Beginning at 12 weeks of age, a subset of offspring were transitioned to a high-fat diet (HFD). Results demonstrated that prenatal exposure to gutkha followed by an HFD in adulthood significantly increased the histologic evidence of fatty liver disease only in adult male offspring. Changes in hepatic fibrosis-related cytokines (interleukin (IL)-1b and IL-6) and in hepatic collagen mRNA expression were observed when comparing adult male offspring exposed to gutkha in utero to those not exposed. These findings indicate that maternal use of gutkha during pregnancy affects NAFLD in adult offspring in a sex-dependent manner. FAU - Doherty Lyons, Shannon AU - Doherty Lyons S AUID- ORCID: 0000-0002-0819-5282 AD - Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Blum, Jason L AU - Blum JL AD - Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA. AD - Product Safety Labs, Dayton, NJ 08810, USA. FAU - Hoffman-Budde, Carol AU - Hoffman-Budde C AD - Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Tijerina, Pamela B AU - Tijerina PB AUID- ORCID: 0000-0002-4280-3042 AD - Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA. FAU - Fiel, M Isabel AU - Fiel MI AD - Department of Pathology, Molecular and Cell-Based Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - J Conklin, Daniel AU - J Conklin D AD - American Heart Association-Tobacco Regulation and Addiction Center, University of Louisville, Kentucky, KY 40202, USA. FAU - Gany, Francesca AU - Gany F AD - Department of Psychiatry and Behavioral Sciences, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. FAU - Odin, Joseph A AU - Odin JA AD - Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. FAU - Zelikoff, Judith T AU - Zelikoff JT AD - Department of Environmental Medicine, New York University School of Medicine, New York, NY 10010, USA. LA - eng GR - U54HL120163/NH/NIH HHS/United States GR - P30 CA008748/CA/NCI NIH HHS/United States GR - P30 GM127607/GM/NIGMS NIH HHS/United States GR - ES000260/ES/NIEHS NIH HHS/United States GR - R01 HL122676/HL/NHLBI NIH HHS/United States GR - P20 GM103492/GM/NIGMS NIH HHS/United States GR - GM103492/NH/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20201028 PL - Switzerland TA - Int J Environ Res Public Health JT - International journal of environmental research and public health JID - 101238455 RN - 0 (Cytokines) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Collagen MH - Cytokines MH - Diet, High-Fat MH - Female MH - Liver/physiopathology MH - Male MH - Mice MH - *Non-alcoholic Fatty Liver Disease/chemically induced MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - *Tobacco, Smokeless/toxicity PMC - PMC7662769 OTO - NOTNLM OT - developmental origins of health and disease OT - gutkha OT - hepatic OT - liver disease OT - smokeless tobacco COIS- The authors declare no conflict of interest. EDAT- 2020/11/01 06:00 MHDA- 2021/01/23 06:00 PMCR- 2020/11/01 CRDT- 2020/10/31 01:01 PHST- 2020/08/25 00:00 [received] PHST- 2020/10/07 00:00 [revised] PHST- 2020/10/15 00:00 [accepted] PHST- 2020/10/31 01:01 [entrez] PHST- 2020/11/01 06:00 [pubmed] PHST- 2021/01/23 06:00 [medline] PHST- 2020/11/01 00:00 [pmc-release] AID - ijerph17217895 [pii] AID - ijerph-17-07895 [pii] AID - 10.3390/ijerph17217895 [doi] PST - epublish SO - Int J Environ Res Public Health. 2020 Oct 28;17(21):7895. doi: 10.3390/ijerph17217895.