- 作者：Sarah J. Barilovits ; Ph.D.a ; b ; Kimberly J. Newsom ; Ph.D.a ; Justin S. Bickford ; Ph.D.a ; Dawn E. Beachy ; B.F.A.a ; Alice Rhoton-Vlasak ; M.D.c ; Harry S. Nick ; Ph.D.a ; b ; hnick@ufl.edu" class="auth_mail
- 关键词：2-Deoxyglucose ; follicle activation ; Foxo3 ; nutrient deprivation ; ovarian reserve
- 刊名：Fertility and Sterility
- 出版年：May 2014
- 年：2014
- 卷：101
- 期：5
- 页码：1450-1457.e4
- 全文大小：1886 K
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.