Characterization of FOXO1,3 and 4 transcription factors in ovaries of fetal, prepubertal and adult rhesus macaques

Research output: Contribution to journalArticle

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Abstract

The phosphoinositide 3-kinase/AKT (protein kinase B) signaling pathway negatively regulates follicle activation via the forkhead box O (FOXO) transcription factor in rodents. FOXO3 knockout mice exhibit global activation of primordial follicles leading to early depletion of ovarian follicles and subsequent infertility. Whether a similar mechanism for follicle activation exists in the primate ovary is unclear. In the current study, protein localization of FOXO1, 3, and 4 as well as their upstream regulator, AKT/p-AKT, was examined in rhesus macaque ovaries of three developmental stages: fetal, prepubertal, and adult. FOXO1 protein is expressed in granulosa cells of fetal, prepubertal, and adult ovaries. FOXO3 is distributed sparsely in the mitotically active germ cells, but its expression decreases following follicle formation in the macaque fetal ovary. In addition, FOXO3 is seldom with interanimal variation in the prepubertal ovary and is absent in the adult ovary. FOXO4 is nondetectable in fetal ovaries, although it is expressed in some theca cells of antral follicles and some stromal cells in prepubertal and adult ovaries. Our results suggest that the regulation and/or function of FOXO3 in the primate primordial follicle may differ than that of the rodent. Nevertheless, AKT/p-AKT is expressed in macaque primordial oocytes, suggesting that similar upstream events but different downstream effects may regulate primordial follicle activation in nonhuman primates compared to rodents. Elucidation of the mechanism responsible for follicle activation in primates will be crucial for understanding primary ovarian insufficiency, improving female fertility, and applying techniques for in vitro maturation of follicles for fertility preservation in cancer survivors.

Original languageEnglish (US)
Article numberiox034
Pages (from-to)1052-1059
Number of pages8
JournalBiology of Reproduction
Volume96
Issue number5
DOIs
StatePublished - May 1 2017

Fingerprint

Transcription Factor 3
Macaca mulatta
Ovary
Primates
Rodentia
Macaca
Fertility Preservation
Theca Cells
Primary Ovarian Insufficiency
Forkhead Transcription Factors
Proto-Oncogene Proteins c-akt
1-Phosphatidylinositol 4-Kinase
Ovarian Follicle
Granulosa Cells
Stromal Cells
Knockout Mice
Germ Cells
Infertility
Oocytes
Fertility

Keywords

  • AKT
  • FOXO1
  • FOXO3
  • FOXO4
  • Nonhuman primate
  • Ovary
  • Primordial follicle

ASJC Scopus subject areas

  • Cell Biology

Cite this

Characterization of FOXO1,3 and 4 transcription factors in ovaries of fetal, prepubertal and adult rhesus macaques. / Ting, Alison; Zelinski, Mary.

In: Biology of Reproduction, Vol. 96, No. 5, iox034, 01.05.2017, p. 1052-1059.

Research output: Contribution to journalArticle

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