An international network (PlaNet) to evaluate a human placental testing platform for chemicals safety testing in pregnancy

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• 作者：Paul Brownbill^a ; ^b ; ^{paul.brownbill@manchester.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Igor Chernyavsky^c ; ^{igor.chernyavsky@manchester.ac.uk" class="auth_mail" title="E-mail the corresponding author} ; Barbara Bottalico^d ; ^{barbarabottalico28@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Gernot Desoye^e ; ^{gernot.desoye@medunigraz.at" class="auth_mail" title="E-mail the corresponding author} ; Stefan Hansson^d ; ^{stefan.hansson@med.lu.se" class="auth_mail" title="E-mail the corresponding author} ; Gerry Kenna^f ; ^{gerry@safermedicines.org" class="auth_mail" title="E-mail the corresponding author} ; Lisbeth E. Knudsen^g ; ^{liek@sund.ku.dk" class="auth_mail" title="E-mail the corresponding author} ; Udo R. Markert^h ; ^{udo.markert@med.uni-jena.de" class="auth_mail" title="E-mail the corresponding author} ; Nicola Powles-Gloverⁱ ; ^{Nicola.PowlesGlover@astrazeneca.com" class="auth_mail" title="E-mail the corresponding author} ; Henning Schneider^j ; ^{henning.schneider@hispeed.ch" class="auth_mail" title="E-mail the corresponding author} ; Lopa Leach^k ; ^{Lopa.Leach@nottingham.ac.uk" class="auth_mail" title="E-mail the corresponding author}
• 关键词：PlaNet ; placentology network ; HPTSs ; human placental test systems ; FDA ; Food and Drug Administration ; EMA ; European Medicines Agency ; PLLR ; pregnancy and lactation labelling rule ; IVS ; intervillous space ; HUVEC ; human umbilical vein endothelial cell ; NET ; norepinephrine transporter ; EMT ; extra-neural monoamine transporter ; VMAT2 ; vesicular monoamine transporter 2 ; NOAEL ; no observed adverse effect level ; LOAEL ; lowest observable adverse effect level ; DART ; development and reproductive toxicology
• 刊名：Reproductive Toxicology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：64
• 期：Complete
• 页码：191-202
• 全文大小：597 K

文摘

The human placenta is a critical life-support system that nourishes and protects a rapidly growing fetus; a unique organ, species specific in structure and function. We consider the pressing challenge of providing additional advice on the safety of prescription medicines and environmental exposures in pregnancy and how m>ex vivom> and m>in vitrom> human placental models might be advanced to reproducible human placental test systems (HPTSs), refining a weight of evidence to the guidance given around compound risk assessment during pregnancy. The placental pharmacokinetics of xenobiotic transfer, dysregulated placental function in pregnancy-related pathologies and influx/efflux transporter polymorphisms are a few caveats that could be addressed by HPTSs, not the specific focus of current mammalian reproductive toxicology systems. An international consortium, “PlaNet”, will bridge academia, industry and regulators to consider screen ability and standardisation issues surrounding these models, with proven reproducibility for introduction into industrial and clinical practice.