{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T20:17:36Z","timestamp":1785529056739,"version":"3.56.0"},"reference-count":192,"publisher":"Bioscientifica","issue":"2","license":[{"start":{"date-parts":[[2017,8,1]],"date-time":"2017-08-01T00:00:00Z","timestamp":1501545600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2017,8]]},"abstract":"<jats:p>\n                    Placental dysfunction underlies major obstetric diseases such as pre-eclampsia and fetal growth restriction (FGR). Whilst there has been a little progress in prophylaxis, there are still no treatments for placental dysfunction in normal obstetric practice. However, a combination of increasingly well-described\n                    <jats:italic>in vitro<\/jats:italic>\n                    systems for studying the human placenta, together with the availability of more appropriate animal models of pre-eclampsia and FGR, has facilitated a recent surge in work aimed at repurposing drugs and therapies, developed for other conditions, as treatments for placental dysfunction. This review: (1) highlights potential candidate drug targets in the placenta \u2013 effectors of improved uteroplacental blood flow, anti-oxidants, heme oxygenase induction, inhibition of HIF, induction of cholesterol synthesis pathways, increasing insulin-like growth factor II availability; (2) proposes an experimental pathway for taking a potential drug or treatment for placental dysfunction from concept through to early phase clinical trials, utilizing techniques for studying the human placenta\n                    <jats:italic>in vitro<\/jats:italic>\n                    and small animal models, particularly the mouse, for\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies; (3) describes the data underpinning sildenafil citrate and adenovirus expressing vascular endothelial growth as potential treatments for placental dysfunction and summarizes recent research on other potential treatments. The importance of sharing information from such studies even when no effect is found, or there is an adverse outcome, is highlighted. Finally, the use of adenoviral vectors or nanoparticle carriers coated with homing peptides to selectively target drugs to the placenta is highlighted: such delivery systems could improve efficacy and reduce the side effects of treating the dysfunctional placenta.\n                  <\/jats:p>","DOI":"10.1530\/joe-17-0185","type":"journal-article","created":{"date-parts":[[2017,5,8]],"date-time":"2017-05-08T20:50:18Z","timestamp":1494276618000},"page":"R81-R97","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":57,"title":["Treating the dysfunctional placenta"],"prefix":"10.1530","volume":"234","author":[{"given":"Colin P","family":"Sibley","sequence":"first","affiliation":[{"name":"1Maternal and Fetal Health Research Centre, Division of Developmental Biology and Medicine, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK"},{"name":"2St Mary\u2019s Hospital, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref241","first-page":"720.e701","article-title":"Safety and pharmacokinetics of pravastatin used for the prevention of preeclampsia in high-risk pregnant women: a pilot randomized controlled trial","volume":"214","year":"2016","journal-title":"American Journal of Obstetrics and Gynecology"},{"key":"ref1751","first-page":"33","article-title":"The programming power of the placenta","volume":"7","year":"2016","journal-title":"Frontiers in Physiology"},{"key":"ref111","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s12884-016-0902-3","article-title":"Effects of simvastatin, rosuvastatin and pravastatin on soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sENG) secretion from human umbilical vein endothelial cells, primary trophoblast cells and 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