Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Hsu, Chien-Ning, Hou, Chih-Yao, Lee, Chien-Te, Chang-Chien, Guo-Ping, Lin, Sufan, Tain, You-Lin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467313/
https://www.ncbi.nlm.nih.gov/pubmed/34578924
http://dx.doi.org/10.3390/nu13093041
_version_ 1784573365496840192
author Hsu, Chien-Ning
Hou, Chih-Yao
Lee, Chien-Te
Chang-Chien, Guo-Ping
Lin, Sufan
Tain, You-Lin
author_facet Hsu, Chien-Ning
Hou, Chih-Yao
Lee, Chien-Te
Chang-Chien, Guo-Ping
Lin, Sufan
Tain, You-Lin
author_sort Hsu, Chien-Ning
collection PubMed
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 (n = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced α-diversity, increased the Firmicutes to Bacteroidetes 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.
format Online
Article
Text
id pubmed-8467313
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-84673132021-09-27 Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure Hsu, Chien-Ning Hou, Chih-Yao Lee, Chien-Te Chang-Chien, Guo-Ping Lin, Sufan Tain, You-Lin Nutrients Article 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 (n = 8/group) were sacrificed at the age of 12 weeks. Perinatal TCDD exposure caused hypertension in adult male offspring coinciding with reduced α-diversity, increased the Firmicutes to Bacteroidetes 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. MDPI 2021-08-30 /pmc/articles/PMC8467313/ /pubmed/34578924 http://dx.doi.org/10.3390/nu13093041 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hsu, Chien-Ning
Hou, Chih-Yao
Lee, Chien-Te
Chang-Chien, Guo-Ping
Lin, Sufan
Tain, You-Lin
Maternal 3,3-Dimethyl-1-Butanol Therapy Protects Adult Male Rat Offspring against Hypertension Programmed by Perinatal TCDD Exposure
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467313/
https://www.ncbi.nlm.nih.gov/pubmed/34578924
http://dx.doi.org/10.3390/nu13093041
work_keys_str_mv AT hsuchienning maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure
AT houchihyao maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure
AT leechiente maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure
AT changchienguoping maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure
AT linsufan maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure
AT tainyoulin maternal33dimethyl1butanoltherapyprotectsadultmaleratoffspringagainsthypertensionprogrammedbyperinataltcddexposure