To demonstrate that a small molecule can induce the transcription factor Foxo3 in the ovary and lead to inhibition of follicle activation.
Design
Cell culture, organ culture, and animal studies.
Setting
University-based laboratory.
Animal(s)
23 female C57BL/6 mice.
Intervention(s)
Human ovary cells and mouse ovaries in culture treated with 2-deoxyglucose (2-DG) to mimic glucose deprivation, and mice intraperitoneally injected with 100 mg/kg, 300 mg/kg, or 600 mg/kg 2-DG daily for 2 weeks.
Main Outcome Measure(s)
In cell and organ culture, Foxo3 expression analyzed by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR); in treated animals, expression of genes regulated by nutrient deprivation (Foxo3, ATF4, GRP78, CHOP, ASNS, c-Myc) measured in brain, kidney, and ovary by qRT-PCR; and ovarian follicles histologically classified and counted.
Result(s)
Foxo3 expression is induced by 2-DG at both the mRNA and protein level in human ovarian cell culture, possibly through ATF4-dependent gene regulation. Foxo3 expression is also induced by 2-DG in ovarian organ culture. Treatment of mice with 100 mg/kg 2-DG resulted in a 2.6 fold induction of Foxo3 in the ovary and a 58% decrease in type 3a primary follicles.
Conclusion(s)
Expression of Foxo3 is induced by nutrient deprivation in cell culture, organ culture, and in vivo. In mice, 2-DG treatment results in an inhibition of primordial follicle activation. These data indicate that Foxo3 induction by 2-DG may be useful for fertility preservation.
Key Words
2-Deoxyglucose
follicle activation
Foxo3
nutrient deprivation
ovarian reserve
Cited by (0)
S.J.B. discloses patent 61/407,510 pending to University of Florida. K.J.N. discloses patent 61/407,510 pending to University of Florida. J.S.B. discloses patent 61/407,510 pending to University of Florida. D.E.B. discloses patent 61/407,510 pending to University of Florida. A.R.-V. has nothing to disclose. H.S.N. discloses patent 61/407,510 pending to University of Florida.
Supported by the National Institutes of Health, National Heart, Lung, and Blood Institute (Grant R01-HL-39593, to H.S.N.), and the National Institute of Diabetes and Digestive and Kidney Diseases (Grant T32-DK-007518, to S.J.B.).
