Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure
Maternal exposure to environmental pollutants affects fetal development, which can result in hypertension in adulthood. Gut microbiota-derived metabolite trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and short chain fatty acids (SCFAs) have been associated with hypertension. We tested a hypot...
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MDPI AG
2021-08-01
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| Series: | Nutrients |
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| Online Access: | https://www.mdpi.com/2072-6643/13/9/3041 |
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| author | Chien-Ning Hsu Chih-Yao Hou Chien-Te Lee Guo-Ping Chang-Chien Sufan Lin You-Lin Tain |
| author_facet | Chien-Ning Hsu Chih-Yao Hou Chien-Te Lee Guo-Ping Chang-Chien Sufan Lin You-Lin Tain |
| author_sort | Chien-Ning Hsu |
| collection | DOAJ |
| description | Maternal exposure to environmental pollutants affects fetal development, which can result in hypertension in adulthood. Gut microbiota-derived metabolite trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and short chain fatty acids (SCFAs) have been associated with hypertension. We tested a hypothesis that maternal 3,3-Dimethyl-1-butanol (DMB, a TMA inhibitor) therapy prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure-induced hypertension in adult offspring relevant to alterations of gut microbiota-derived metabolites, the mediation of aryl hydrocarbon receptor (AHR) signaling, and the renin-angiotensin system (RAS). Pregnant Sprague-Dawley rats were given weekly oral dose of TCDD 200 ng/kg for four doses (T), 1% DMB in drinking water (D), TCDD + DMB (TD), or vehicle (C) in pregnancy and lactation periods. Male progeny (<i>n</i> = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced <i>α</i>-diversity, increased the <i>Firmicutes</i> to <i>Bacteroidetes</i> ratio, less abundant beneficial bacteria, impaired SCFA receptors’ expression, the activation of AHR signaling, and the aberrant activation of the RAS. Treatment with DMB during pregnancy and lactation rescued hypertension induced by perinatal TCDD exposure. This was accompanied by reshaping gut microbiota, mediating TMA-TMAO metabolic pathway, increasing acetic acid and its receptors, and restoring the AHR and RAS pathway. Our data provide new insights into the therapeutic potential of DMB, a microbiome-based metabolite treatment, for the prevention of hypertension of developmental origins. |
| first_indexed | 2024-03-10T07:21:45Z |
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| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T07:21:45Z |
| publishDate | 2021-08-01 |
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| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-f38633eaec694c848461370245c1dbcd2023-11-22T14:36:31ZengMDPI AGNutrients2072-66432021-08-01139304110.3390/nu13093041Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD ExposureChien-Ning Hsu0Chih-Yao Hou1Chien-Te Lee2Guo-Ping Chang-Chien3Sufan Lin4You-Lin Tain5Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanDepartment of Seafood Science, National Kaohsiung University of Science and Technology, Kaohsiung 811, TaiwanDivision of Nephrology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833, TaiwanCenter for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, TaiwanCenter for Environmental Toxin and Emerging-Contaminant Research, Cheng Shiu University, Kaohsiung 833, TaiwanDepartment of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Kaohsiung 833, TaiwanMaternal exposure to environmental pollutants affects fetal development, which can result in hypertension in adulthood. Gut microbiota-derived metabolite trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and short chain fatty acids (SCFAs) have been associated with hypertension. We tested a hypothesis that maternal 3,3-Dimethyl-1-butanol (DMB, a TMA inhibitor) therapy prevents 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure-induced hypertension in adult offspring relevant to alterations of gut microbiota-derived metabolites, the mediation of aryl hydrocarbon receptor (AHR) signaling, and the renin-angiotensin system (RAS). Pregnant Sprague-Dawley rats were given weekly oral dose of TCDD 200 ng/kg for four doses (T), 1% DMB in drinking water (D), TCDD + DMB (TD), or vehicle (C) in pregnancy and lactation periods. Male progeny (<i>n</i> = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced <i>α</i>-diversity, increased the <i>Firmicutes</i> to <i>Bacteroidetes</i> ratio, less abundant beneficial bacteria, impaired SCFA receptors’ expression, the activation of AHR signaling, and the aberrant activation of the RAS. Treatment with DMB during pregnancy and lactation rescued hypertension induced by perinatal TCDD exposure. This was accompanied by reshaping gut microbiota, mediating TMA-TMAO metabolic pathway, increasing acetic acid and its receptors, and restoring the AHR and RAS pathway. Our data provide new insights into the therapeutic potential of DMB, a microbiome-based metabolite treatment, for the prevention of hypertension of developmental origins.https://www.mdpi.com/2072-6643/13/9/3041gut microbiotaaryl hydrocarbon receptor3,3-dimethyl-1-butanoldevelopmental origins of health and disease (DOHaD)hypertensionshort chain fatty acid |
| spellingShingle | Chien-Ning Hsu Chih-Yao Hou Chien-Te Lee Guo-Ping Chang-Chien Sufan Lin You-Lin Tain Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure Nutrients gut microbiota aryl hydrocarbon receptor 3,3-dimethyl-1-butanol developmental origins of health and disease (DOHaD) hypertension short chain fatty acid |
| title | Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure |
| title_full | Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure |
| title_fullStr | Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure |
| title_full_unstemmed | Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure |
| title_short | Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure |
| title_sort | maternal 3 3 dimethyl 1 butanol therapy protects adult male rat offspring against hypertension programmed by perinatal tcdd exposure |
| topic | gut microbiota aryl hydrocarbon receptor 3,3-dimethyl-1-butanol developmental origins of health and disease (DOHaD) hypertension short chain fatty acid |
| url | https://www.mdpi.com/2072-6643/13/9/3041 |
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