Alterations in prostate morphogenesis in male rat offspring after maternal exposure to Di-n-butyl-phthalate (DBP).
Prostate morphogenesis is regulated by androgens hormones and modulated by morphogenetic proteins such as Bone Morphogenetic Proteins (BMPs). This study aims to investigate the effects on prostate development in male offspring and differentiation after gestational and lactational maternal exposure to Di-n-butyl-phthalate (DBP), an important environmental contamination. Pregnant Wistar rats received 100 or 500mg/kg of DBP (DBP100 and DBP500), by gavage, from gestation day 15 (GD15) until postnatal day 21 (PND21). The pups were euthanized on PND1 and PND21. Anogenital distance and testosterone levels decreased in animals from exposed mothers (DBP100 and 500) on PND1. A three-dimensional reconstruction model of the prostatic urethra showed reduction in the prostatic buds in the DBP500 group. AR expression and α-actin immunoreactivity decreased, and BMP-4 expression was lower on PND1 for DBP500. These results showed that DBP exposure, especially at a higher dose, delayed prostate morphogenesis by reducing the testosterone/AR axis and BMP-4 expression.
Department of Anatomy, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil. Electronic address: talitamello.tms@gmail.com.
Talita
T
de Mello Santos
Department of Morphology, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.
Lívia Teresa Ribeiro
LTR
da Silveira
Department of Morphology, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.
Jaqueline Carvalho
JC
Rinaldi
Department of Morphology, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.
Wellerson Rodrigo
WR
Scarano
Department of Anatomy, Institute of Biosciences, Univi Estadual Paulista/UNESP, Botucatu, SP, Brazil.
Raquel Fantin
RF
Domeniconi
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism; D003993:Dibutyl Phthalate / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D007774:Lactation; D008297:Male; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011467:Prostate / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D017208:Rats, Wistar; D011944:Receptors, Androgen / Q000378:metabolism; D013739:Testosterone / Q000097:blood
D000726:Androgen Antagonists; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D004785:Environmental Pollutants; D011944:Receptors, Androgen; D003993:Dibutyl Phthalate; D013739:Testosterone
Androgen receptor; Antiandrogenic; Di-n-butyl-phthalate (DBP) BMP-4; Prostate development; Testosterone; α-actin