Characterization of a mechanism to inhibit ovarian follicle activation

Foxo3 is induced in cell and organ culture, and a mouse model, by 2-deoxyglucose (2-DG). In mice, 2-DG treatment results in reduced activation of primordial follicles.

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Authors

Sarah J. Barilovits, Ph.D., Kimberly J. Newsom, Ph.D., Justin S. Bickford, Ph.D., Dawn E. Beachy, B.F.A., Alice Rhoton-Vlasak, M.D., Harry S. Nick, Ph.D.

Volume 101, Issue 5, Pages 1450–1457.e4

Abstract

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.

Read the full text at: http://www.fertstert.org/article/S0015-0282(14)00070-3/fulltext


Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.

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