Pre-natal exposure of mice to bisphenol A elicits an endometriosis-like phenotype in female offspring.
Endometriosis is a chronic gynecological disease characterized by the growth of endometrial tissue outside the uterine cavity. Exposure to endocrine disruptors during critical period of development causes long-lasting effects, being the genital system one of the targets. This study describes the effects on female genital system caused by developmental exposure to the endocrine-disrupting chemical bisphenol A (BPA) during pre- and peri-natal development in mice. To this end, timed pregnant Balb-C mice were treated from day 1 of gestation to 7 days after delivery with BPA (100, or 1000 microg/kg/day). After delivery, pups were held for 3 months; then, pelvic organs were analyzed in their entirety and livers of both pups and moms were studied for the presence of BPA. We found in the adipose tissue surrounding the genital tracts of a consistent number of treated animals, endometriosis-like structure with the presence of both glands and stroma and expressing both estrogen receptor and HOXA-10. Moreover, cystic ovaries, adenomatous hyperplasia with cystic endometrial hyperplasia and atypical hyperplasia were significantly more frequent in treated animals respect to the controls. Finally, BPA was found in the livers of exposed moms and female offspring. In conclusion, we describe for the first time an endometriosis-like phenotype in mice, elicited by pre-natal exposition to BPA. This observation may induce to thoroughly reconsider the pathogenesis and treatment of endometriosis, considering the high incidence of endometriosis and the problems caused by associated infertility.
Signorile
Pietro G
PG
Fondazione Italiana Endometriosi, Rome, Italy.
Spugnini
Enrico P
EP
Mita
Luigi
L
Mellone
Pasquale
P
D'Avino
Alfredo
A
Bianco
Mariangela
M
Diano
Nadia
N
Caputo
Lucia
L
Rea
Francesca
F
Viceconte
Rosa
R
Portaccio
Marianna
M
Viggiano
Emanuela
E
Citro
Gennaro
G
Pierantoni
Riccardo
R
Sica
Vincenzo
V
Vincenzi
Bruno
B
Mita
Damiano G
DG
Baldi
Feliciano
F
Baldi
Alfonso
A
D000818:Animals; D001559:Benzhydryl Compounds; D004715:Endometriosis / Q000139:chemically induced* / Q000209:etiology* / Q000378:metabolism; D005260:Female; D005836:Genitalia, Female / Q000187:drug effects / Q000196:embryology; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D010636:Phenols / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D014599:Uterus / Q000187:drug effects / Q000196:embryology; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds