Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner

Abstract Introduction Normal placental vascular development is influenced by inflammatory, angiogenic and apoptotic processes, which may be modulated by choline through its role in membrane biosynthesis, cellular signaling and gene expression regulation. The current study examined the effect of mate...

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Veröffentlicht in:Placenta (Eastbourne) 2017-05, Vol.53, p.57-65
Hauptverfasser: Kwan, Sze Ting (Cecilia), King, Julia H, Yan, Jian, Jiang, Xinyin, Wei, Emily, Fomin, Vladislav G, Roberson, Mark S, Caudill, Marie A
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container_issue
container_start_page 57
container_title Placenta (Eastbourne)
container_volume 53
creator Kwan, Sze Ting (Cecilia)
King, Julia H
Yan, Jian
Jiang, Xinyin
Wei, Emily
Fomin, Vladislav G
Roberson, Mark S
Caudill, Marie A
description Abstract Introduction Normal placental vascular development is influenced by inflammatory, angiogenic and apoptotic processes, which may be modulated by choline through its role in membrane biosynthesis, cellular signaling and gene expression regulation. The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy. Method Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses. Results The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript ( P  ≤ 0.05) and protein ( P  ≤ 0.06) expression of TNF-a and IL-1β in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 ( P  = 0.045) and E18.5 ( P  = 0.067) but increased Il1b at E15.5 ( P  = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 ( P  = 0.034; 4X versus 2X) and E18.5 ( P  = 0.026; 4X versus 1X). MCS decreased ( P  = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger ( P  ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation. Discussion MCS during murine pregnancy has fetal sex-specific effects on placental inflammation and angiogenesis, with possible consequences on placental vascular development.
doi_str_mv 10.1016/j.placenta.2017.03.019
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The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy. Method Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses. Results The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript ( P  ≤ 0.05) and protein ( P  ≤ 0.06) expression of TNF-a and IL-1β in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 ( P  = 0.045) and E18.5 ( P  = 0.067) but increased Il1b at E15.5 ( P  = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 ( P  = 0.034; 4X versus 2X) and E18.5 ( P  = 0.026; 4X versus 1X). MCS decreased ( P  = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger ( P  ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation. Discussion MCS during murine pregnancy has fetal sex-specific effects on placental inflammation and angiogenesis, with possible consequences on placental vascular development.</description><identifier>ISSN: 0143-4004</identifier><identifier>EISSN: 1532-3102</identifier><identifier>DOI: 10.1016/j.placenta.2017.03.019</identifier><identifier>PMID: 28487022</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Angiogenesis ; Animals ; Apoptosis - drug effects ; Biomarkers - metabolism ; Choline ; Choline - administration &amp; dosage ; Choline - pharmacokinetics ; Cytokines - metabolism ; Dietary Supplements ; Drug Evaluation, Preclinical ; Endoglin - metabolism ; Female ; Fetal sex ; Inflammation ; Internal Medicine ; Lipotropic Agents - administration &amp; dosage ; Lipotropic Agents - pharmacokinetics ; Liver - metabolism ; Male ; Mice ; Neovascularization, Physiologic - drug effects ; Obstetrics and Gynecology ; Placenta ; Placenta - blood supply ; Placenta - drug effects ; Placenta - immunology ; Placenta - metabolism ; Pregnancy ; Random Allocation ; Vascular Endothelial Growth Factor Receptor-1 - metabolism</subject><ispartof>Placenta (Eastbourne), 2017-05, Vol.53, p.57-65</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. 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The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy. Method Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses. Results The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript ( P  ≤ 0.05) and protein ( P  ≤ 0.06) expression of TNF-a and IL-1β in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 ( P  = 0.045) and E18.5 ( P  = 0.067) but increased Il1b at E15.5 ( P  = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 ( P  = 0.034; 4X versus 2X) and E18.5 ( P  = 0.026; 4X versus 1X). MCS decreased ( P  = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger ( P  ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation. 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King, Julia H ; Yan, Jian ; Jiang, Xinyin ; Wei, Emily ; Fomin, Vladislav G ; Roberson, Mark S ; Caudill, Marie A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c526t-55541dc760137386ec04fd8d46fc1d2574d27262f0fdb979f042b884c4d390263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Angiogenesis</topic><topic>Animals</topic><topic>Apoptosis - drug effects</topic><topic>Biomarkers - metabolism</topic><topic>Choline</topic><topic>Choline - administration &amp; dosage</topic><topic>Choline - pharmacokinetics</topic><topic>Cytokines - metabolism</topic><topic>Dietary Supplements</topic><topic>Drug Evaluation, Preclinical</topic><topic>Endoglin - metabolism</topic><topic>Female</topic><topic>Fetal sex</topic><topic>Inflammation</topic><topic>Internal Medicine</topic><topic>Lipotropic Agents - administration &amp; dosage</topic><topic>Lipotropic Agents - pharmacokinetics</topic><topic>Liver - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Neovascularization, Physiologic - drug effects</topic><topic>Obstetrics and Gynecology</topic><topic>Placenta</topic><topic>Placenta - blood supply</topic><topic>Placenta - drug effects</topic><topic>Placenta - immunology</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Random Allocation</topic><topic>Vascular Endothelial Growth Factor Receptor-1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwan, Sze Ting (Cecilia)</creatorcontrib><creatorcontrib>King, Julia H</creatorcontrib><creatorcontrib>Yan, Jian</creatorcontrib><creatorcontrib>Jiang, Xinyin</creatorcontrib><creatorcontrib>Wei, Emily</creatorcontrib><creatorcontrib>Fomin, Vladislav G</creatorcontrib><creatorcontrib>Roberson, Mark S</creatorcontrib><creatorcontrib>Caudill, Marie A</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Placenta (Eastbourne)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwan, Sze Ting (Cecilia)</au><au>King, Julia H</au><au>Yan, Jian</au><au>Jiang, Xinyin</au><au>Wei, Emily</au><au>Fomin, Vladislav G</au><au>Roberson, Mark S</au><au>Caudill, Marie A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner</atitle><jtitle>Placenta (Eastbourne)</jtitle><addtitle>Placenta</addtitle><date>2017-05-01</date><risdate>2017</risdate><volume>53</volume><spage>57</spage><epage>65</epage><pages>57-65</pages><issn>0143-4004</issn><eissn>1532-3102</eissn><abstract>Abstract Introduction Normal placental vascular development is influenced by inflammatory, angiogenic and apoptotic processes, which may be modulated by choline through its role in membrane biosynthesis, cellular signaling and gene expression regulation. The current study examined the effect of maternal choline supplementation (MCS) on placental inflammatory, angiogenic and apoptotic processes during murine pregnancy. Method Pregnant dams were randomized to receive 1, 2 or 4 times (X) the normal choline content of rodent diets, and tissues were harvested on embryonic day (E) 10.5, 12.5, 15.5 or 18.5 for gene expression, protein abundance and immunohistochemical analyses. Results The choline-induced changes in the inflammatory and angiogenic markers were a function of fetal sex. Specifically, 4X (versus 1X) choline reduced the transcript ( P  ≤ 0.05) and protein ( P  ≤ 0.06) expression of TNF-a and IL-1β in the male placentas at E10.5 and E18.5, respectively. In the female placentas, 4X (versus 1X) choline modulated the transcript expression of Il1b in a biphasic pattern with reduced Il1b at E12.5 ( P  = 0.045) and E18.5 ( P  = 0.067) but increased Il1b at E15.5 ( P  = 0.031). MCS also induced an upregulation of Vegfa expression in the female placentas at E15.5 ( P  = 0.034; 4X versus 2X) and E18.5 ( P  = 0.026; 4X versus 1X). MCS decreased ( P  = 0.011; 4X versus 1X) placental apoptosis at E10.5. Additionally, the luminal area of the maternal spiral arteries was larger ( P  ≤ 0.05; 4X versus 1X) in response to extra choline throughout gestation. Discussion MCS during murine pregnancy has fetal sex-specific effects on placental inflammation and angiogenesis, with possible consequences on placental vascular development.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>28487022</pmid><doi>10.1016/j.placenta.2017.03.019</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7192-5743</orcidid><oa>free_for_read</oa></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
subjects Angiogenesis
Animals
Apoptosis - drug effects
Biomarkers - metabolism
Choline
Choline - administration & dosage
Choline - pharmacokinetics
Cytokines - metabolism
Dietary Supplements
Drug Evaluation, Preclinical
Endoglin - metabolism
Female
Fetal sex
Inflammation
Internal Medicine
Lipotropic Agents - administration & dosage
Lipotropic Agents - pharmacokinetics
Liver - metabolism
Male
Mice
Neovascularization, Physiologic - drug effects
Obstetrics and Gynecology
Placenta
Placenta - blood supply
Placenta - drug effects
Placenta - immunology
Placenta - metabolism
Pregnancy
Random Allocation
Vascular Endothelial Growth Factor Receptor-1 - metabolism
title Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner
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