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Placental compromise is probably the cause of fetal growth retardation in gestational testosterone-treated sheep. This study tested whether testosterone excess compromises placental differentiation by its androgenic action and\/or via altered insulin sensitivity. A comparative approach of studying gestational testosterone (aromatizable androgen) against dihydrotestosterone (non-aromatizable androgen) or testosterone plus androgen antagonist, flutamide, was used to determine whether the effects of testosterone on placental differentiation were programed by its androgenic actions. Co-treatment of testosterone with the insulin sensitizer, rosiglitazone, was used to establish whether the effects of gestational testosterone on placentome differentiation involved compromised insulin sensitivity. Parallel cohorts of pregnant females were maintained for lambing and the birth weight of their offspring was recorded. Placental studies were conducted on days 65, 90, or 140 of gestation. Results indicated that i) gestational testosterone treatment advances placental differentiation, evident as early as day 65 of gestation, and culminates in low birth weight, ii) placental advancement is facilitated at least in part by androgenic actions of testosterone and is not a function of disrupted insulin homeostasis, and iii) placental advancement, while helping to increase placental efficiency, was insufficient to prevent IUGR and low-birth-weight female offspring. Findings from this study may be of relevance to women with polycystic ovary syndrome, whose reproductive and metabolic phenotype is captured by the gestational testosterone-treated offspring.<\/jats:p>","DOI":"10.1530\/rep-14-0055","type":"journal-article","created":{"date-parts":[[2014,5,20]],"date-time":"2014-05-20T00:41:20Z","timestamp":1400546480000},"page":"199-209","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":56,"title":["Developmental programing: impact of testosterone on placental differentiation"],"prefix":"10.1093","volume":"148","author":[{"given":"E M","family":"Beckett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O","family":"Astapova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T L","family":"Steckler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Veiga-Lopez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V","family":"Padmanabhan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,8,1]]},"reference":[{"key":"2026010712293724800_bib1"},{"key":"2026010712293724800_bib2","doi-asserted-by":"crossref","first-page":"E741","DOI":"10.1152\/ajpendo.00058.2010","article-title":"Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring","volume":"299","author":"Abbott","year":"2010","journal-title":"American Journal of Physiology. 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