title: Selective estrogen receptor alpha activation disrupts sex organ differentiation and induces expression of vitellogenin II and very low-density apolipoprotein II in Japanese quail embryos.
abstract: The Japanese quail (Coturnix japonica) is a widely used model species for studying the roles of steroid hormones in avian sex differentiation. The aim of the present study was to elucidate the significance of estrogen receptors alpha and beta (ERalpha and ERbeta) in normal sex differentiation of the reproductive organs in the Japanese quail and in xenoestrogen-induced disruption of reproductive organ differentiation. Real-time PCR indicated that ERalpha (ESR1) mRNA is expressed in both right and left gonads and Müllerian ducts (MDs) in both sexes during early morphological differentiation. ERbeta (ESR2) transcripts were also detected in gonads and MDs, but at very low levels. Both receptor subtypes were expressed in the liver and may therefore mediate the expression of estrogen-regulated egg-yolk proteins. Aromatase mRNA was expressed at much higher levels in female than male gonads as early as embryonic day 5, indicating early sex differences in estrogen synthesis. Treatment with the ERalpha-selective agonist propyl pyrazole triol showed that frequently reported xenoestrogen effects, such as ovotestis formation, abnormal MD development, and hepatic expression of egg-yolk proteins, were induced by selective activation of ERalpha. Taken together, our results suggest that activation of ERalpha is crucial for estrogen-dependent sex differentiation of the reproductive organs and that ERalpha mediates xenoestrogen-induced toxicity during reproductive development in birds.
authors.affiliation: Department of Environmental Toxicology, Centre for Reproductive Biology in Uppsala, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Mattsson
authors.forename: Jan A
authors.initials: JA
authors.lastname: Olsson
authors.forename: Björn
authors.initials: B
authors.lastname: Brunström
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000032:analysis / Q000378:metabolism*; D001141:Aromatase / Q000235:genetics; D003370:Coturnix; D004789:Enzyme Activation; D047628:Estrogen Receptor alpha / Q000032:analysis / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000032:analysis / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D009095:Mullerian Ducts / Q000033:anatomy & histology / Q000737:chemistry / Q000378:metabolism*; D010053:Ovary / Q000196:embryology; D010636:Phenols; D011498:Protein Precursors / Q000032:analysis / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012733:Sex Differentiation; D013737:Testis / Q000196:embryology; D014819:Vitellogenins / Q000032:analysis / Q000378:metabolism*
chemical_list: D001053:Apolipoproteins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011498:Protein Precursors; D011720:Pyrazoles; D012333:RNA, Messenger; D014819:Vitellogenins; C054949:apolipoprotein II; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D001141:Aromatase