Document Detail


Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep.
MedLine Citation:
PMID:  20739662     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Prenatal testosterone excess in sheep leads to reproductive and metabolic disruptions that mimic those seen in women with polycystic ovary syndrome. Comparison of prenatal testosterone-treated sheep with prenatal dihydrotestosterone-treated sheep suggests facilitation of defects by androgenic as well as androgen-independent effects of testosterone. We hypothesized that the disruptive impact of prenatal testosterone on adult pathology may partially depend on its conversion to estrogen and consequent changes in maternal and fetal endocrine environments. Pregnant Suffolk sheep were administered either cottonseed oil (control) or testosterone propionate in cottonseed oil (100 mg, i.m. twice weekly), from Day 30 to Day 90 of gestation (term is ~147 d). Maternal (uterine) and fetal (umbilical) arterial samples were collected at Days 64-66, 87-90, and 139-140 (range; referred to as D65, D90, and D140, respectively) of gestation. Concentrations of gonadal and metabolic hormones, as well as differentiation factors, were measured using liquid chromatography/mass spectrometer, radioimmunoassay, or ELISA. Findings indicate that testosterone treatment produced maternal and fetal testosterone levels comparable to adult males and D65 control male fetuses, respectively. Testosterone treatment increased fetal estradiol and estrone levels during the treatment period in both sexes, supportive of placental aromatization of testosterone. These steroidal changes were followed by a reduction in maternal estradiol levels at term, a reduction in activin A availability, and induction of intrauterine growth restriction in D140 female fetuses. Overall, our findings provide the first direct evidence in support of the potential for both androgenic as well as estrogenic contribution in the development of adult reproductive and metabolic pathology in prenatal testosterone-treated sheep.
Authors:
Almudena Veiga-Lopez; Teresa L Steckler; David H Abbott; Kathleen B Welch; Puliyur S MohanKumar; David J Phillips; Kent Refsal; Vasantha Padmanabhan
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-08-25
Journal Detail:
Title:  Biology of reproduction     Volume:  84     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-03     Completed Date:  2011-05-16     Revised Date:  2014-11-09    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  87-96     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Glucose
Estrogens / blood,  metabolism
Female
Gene Expression Regulation / physiology
Insulin / blood
Insulin-Like Growth Factor I / metabolism
Leptin / blood
Male
Pregnancy
Prenatal Exposure Delayed Effects
Sheep / embryology*
Testosterone Propionate / blood,  metabolism,  toxicity*
Thyroxine / blood
Triiodothyronine / blood
Grant Support
ID/Acronym/Agency:
P01-HD44232/HD/NICHD NIH HHS; P30 DK089503/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Blood Glucose; 0/Estrogens; 0/Insulin; 0/Leptin; 06LU7C9H1V/Triiodothyronine; 67763-96-6/Insulin-Like Growth Factor I; Q51BO43MG4/Thyroxine; WI93Z9138A/Testosterone Propionate
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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