Manipulation of pre and postnatal androgen environments and anogenital distance in rats

Abstract We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20 mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750 mg/kg/day), or testostero...

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Bibliographic Details
Published in:	Toxicology (Amsterdam) Vol. 368-369; pp. 152 - 161
Main Authors:	Kita, Diogo H, Meyer, Katlyn B, Venturelli, Amanda C, Adams, Rafaella, Machado, Daria L.B, Morais, Rosana N, Swan, Shanna H, Gennings, Chris, Martino-Andrade, Anderson J
Format:	Journal Article
Language:	English
Published:	Ireland Elsevier B.V 10-08-2016
Subjects:	Androgen Antagonists - toxicity Androgens Androgens - physiology Animals Anogenital Distance Anogenital distance (AGD) Anti-androgens Dams DEHP Diethylhexyl Phthalate - toxicity Disease Models, Animal Dose-Response Relationship, Drug Emergency Endocrine Disruptors Exposure Female Flutamide Flutamide - toxicity Gestation Male Males Organ Size - drug effects Penis - abnormalities Penis - drug effects Plasticity Pregnancy Pregnancy Outcome Prenatal Exposure Delayed Effects Rats Spermatids - drug effects Spermatids - metabolism Testis - abnormalities Testis - drug effects Testosterone Testosterone - biosynthesis Vehicles flutamide Anogenital Distance Androgens testosterone DEHP Anogenital distance (AGD) Anti-androgens rats Endocrine Disruptors Testosterone Flutamide Rats
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Summary:	Abstract We examined the anogenital distance (AGD) plasticity in rats through the manipulation of the androgen environment in utero and during puberty. Dams were treated from gestation days 13-20 with vehicle, flutamide (20 mg/kg/day), di-(2-ethylhexyl) phthalate (DEHP, 750 mg/kg/day), or testosterone (1.0 mg/kg/day). After weaning, male pups were randomly assigned to one of four postnatal groups, which received the same treatments given prenatally. Sixteen treatment groups were established based on the combination of pre- and postnatal exposures. The postnatal treatments were conducted from postnatal days 23-53. In utero flutamide and DEHP exposure significantly shortened male AGD, although this effect was more pronounced in flutamide-exposed rats. Postnatal flutamide, DEHP, and testosterone induced slight but significant reductions in male AGD. Our study indicates that AGD is a stable anatomical landmark that reflects the androgen action in utero, although it can also be slightly responsive to changes in the androgen environment following pubertal exposure.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0300-483X 1879-3185
DOI:	10.1016/j.tox.2016.08.021