Estrogen receptor alpha overexpressing mouse antral follicles are sensitive to atresia induced by methoxychlor and its metabolites.
Methoxychlor (MXC) and its metabolites bind to estrogen receptors (ESRs) and increase ovarian atresia. To test whether ESR alpha (ESR1) overexpressing (ESR1 OE) antral follicles are more sensitive to atresia compared to controls, we cultured antral follicles with vehicle, MXC (1-100 μg/ml) or metabolites (0.1-10 μg/ml). Results indicate that MXC and its metabolites significantly increase atresia in ESR1 OE antral follicles at lower doses compared to controls. Activity of pro-apoptotic factor caspase-3/7 was significantly higher in ESR1 OE treated antral follicles compared to controls. ESR1 OE mice dosed with MXC 64 mg/kg/day had an increased percentage of atretic antral follicles compared to controls. Furthermore, pro-caspase-3 levels were found to be significantly lower in ESR1 OE ovaries than controls dosed with MXC 64 mg/kg/day. These data suggest that ESR1 OE ovaries are more sensitive to atresia induced by MXC and its metabolites in vitro and in vivo compared to controls.
Department of Comparative Biosciences, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA. tessiepaulose@gmail.com
Tessie
T
Paulose
Patrick R
PR
Hannon
Jackye
J
Peretz
Zelieann R
ZR
Craig
Jodi A
JA
Flaws
D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008731:Methoxychlor / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics
D051023:BH3 Interacting Domain Death Agonist Protein; C494827:Bax protein, mouse; C494815:Bid protein, mouse; D047628:Estrogen Receptor alpha; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053179:Caspase 7; D008731:Methoxychlor