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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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 & 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</subject><ispartof>Placenta (Eastbourne), 2017-05, Vol.53, p.57-65</ispartof><rights>2017 Elsevier Ltd</rights><rights>Copyright © 2017 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-55541dc760137386ec04fd8d46fc1d2574d27262f0fdb979f042b884c4d390263</citedby><cites>FETCH-LOGICAL-c526t-55541dc760137386ec04fd8d46fc1d2574d27262f0fdb979f042b884c4d390263</cites><orcidid>0000-0002-7192-5743</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0143400417302096$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28487022$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner</title><title>Placenta (Eastbourne)</title><addtitle>Placenta</addtitle><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.</description><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis - drug effects</subject><subject>Biomarkers - metabolism</subject><subject>Choline</subject><subject>Choline - administration & dosage</subject><subject>Choline - pharmacokinetics</subject><subject>Cytokines - metabolism</subject><subject>Dietary Supplements</subject><subject>Drug Evaluation, Preclinical</subject><subject>Endoglin - metabolism</subject><subject>Female</subject><subject>Fetal sex</subject><subject>Inflammation</subject><subject>Internal Medicine</subject><subject>Lipotropic Agents - administration & dosage</subject><subject>Lipotropic Agents - pharmacokinetics</subject><subject>Liver - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Neovascularization, Physiologic - drug effects</subject><subject>Obstetrics and Gynecology</subject><subject>Placenta</subject><subject>Placenta - blood supply</subject><subject>Placenta - drug effects</subject><subject>Placenta - immunology</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Random Allocation</subject><subject>Vascular Endothelial Growth Factor Receptor-1 - metabolism</subject><issn>0143-4004</issn><issn>1532-3102</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk1uFDEQhVsIRIbAFSIfgG7KP_23iUARBKQgFsDa8tjVE0_cdsvuGWW4DheNm2EiYMOqFq73lV-9KooLChUF2rzZVpNTGv2sKga0rYBXQPsnxYrWnJWcAntarIAKXgoAcVa8SGkLAL2g7HlxxjrRtcDYqvj5Wc0YvXJE3wZnPZK0myaH44KebfDE7KL1GzIuBckUceOV1wcyBrNzWZzI6SeOjCreYUwkDMT6walx_MV4TdQUpjkkm4jyhuxV0lkb7Y_jCOuJIgMuhIT3pcEJvcnEzPMe48vi2aBcwle_63nx_cP7b1cfy5sv15-u3t2UumbNXNZ1LajRbQOUt7xrUIMYTGdEM2hqWN0Kw1rWsAEGs-7bfgDB1l0ntDC8B9bw8-LyyJ126xHN4ikqJ6dos6-DDMrKv1-8vZWbsJcdFdAxyIDmCNAxpBRxeNRSkEtscitPy5JLbBK4zLFl4cWfkx9lp5xyw9tjA2b_e4tRJm3RazQ2op6lCfb_My7_Qeict9XK3eEB0zbsljNIksrEJMivy_Est0NbDgz6hj8A2aPHoQ</recordid><startdate>20170501</startdate><enddate>20170501</enddate><creator>Kwan, Sze Ting (Cecilia)</creator><creator>King, Julia H</creator><creator>Yan, Jian</creator><creator>Jiang, Xinyin</creator><creator>Wei, Emily</creator><creator>Fomin, Vladislav G</creator><creator>Roberson, Mark S</creator><creator>Caudill, Marie A</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7192-5743</orcidid></search><sort><creationdate>20170501</creationdate><title>Maternal choline supplementation during murine pregnancy modulates placental markers of inflammation, apoptosis and vascularization in a fetal sex-dependent manner</title><author>Kwan, Sze Ting (Cecilia) ; 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 & 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 & 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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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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