Related Experiment Video
Updated: May 2, 2026
Fertility Preservation in Patients with Severe Ovarian Dysfunction
Published on: March 25, 2021
Characterization of a mechanism to inhibit ovarian follicle activation
Sarah J Barilovits1, Kimberly J Newsom2, Justin S Bickford2
1Department of Neuroscience, College of Medicine, University of Florida, Gainesville, Florida; Department of Biochemistry and Molecular Biology, College of Medicine, University of Florida, Gainesville, Florida.
Objective:
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.
Insights
Nutrient deprivation, using 2-deoxyglucose (2-DG), induces Foxo3 expression in ovarian cells and inhibits primordial follicle activation in mice, suggesting potential for fertility preservation.
Area of Science:
- Reproductive biology and molecular endocrinology.
- Cellular and molecular mechanisms of follicle development.
Background:
- Ovarian follicle activation is a critical process in female reproduction.
- Understanding molecular regulators of follicle activation is key for fertility research.
- Nutrient deprivation can impact cellular processes, including gene expression.
Purpose of the Study:
- To investigate if a small molecule, 2-deoxyglucose (2-DG), can induce the transcription factor Foxo3 in ovarian cells.
- To determine if 2-DG-induced Foxo3 expression inhibits ovarian follicle activation.
- To explore the potential of this mechanism for fertility preservation strategies.
Main Methods:
- Utilized cell culture, organ culture, and animal studies with female C57BL/6 mice.
- Treated human ovarian cells and mouse ovaries with 2-DG to simulate glucose deprivation.
- Administered varying doses of 2-DG to mice and analyzed gene expression (Foxo3, ATF4, etc.) and follicle counts.
Main Results:
- 2-deoxyglucose (2-DG) significantly induced Foxo3 expression at both mRNA and protein levels in human ovarian cells.
- 2-DG treatment also upregulated Foxo3 in ovarian organ cultures.
- In mice, 2-DG administration led to a 2.6-fold increase in ovarian Foxo3 and a 58% reduction in primordial follicle activation.
Conclusions:
- Nutrient deprivation, mimicked by 2-DG, effectively induces Foxo3 expression across in vitro and in vivo models.
- 2-DG treatment in mice inhibits primordial follicle activation, mediated by Foxo3 induction.
- These findings highlight the potential therapeutic application of 2-DG for fertility preservation.
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