Exogenous granulocyte-macrophage colony-stimulating factor promotes follicular development in the newborn rat in vivo

Hum Reprod. 2005 Oct;20(10):2749-56. doi: 10.1093/humrep/dei123. Epub 2005 Jun 15.


Background: Expression and selective cellular localization of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in ovarian tissue imply an autocrine/paracrine role in ovarian function. Evidence indicating a functional role for GM-CSF in ovarian follicular cell function has been provided by studies with GM-CSF knockout (GM-/-) mice, which suggest that GM-CSF influences events associated with murine follicular maturation.

Methods: Immature female rats were treated with GM-CSF, FSH or saline for 5 or 10 days. Ovaries were collected for histologic examination and immunostaining determination of CYP17, a theca cell marker. In addition, ovarian section slides were evaluated by immunofluorescence for CD45, an ovarian leukocyte marker. To investigate the possible mechanism of GM-CSF action on follicular development, theca-interstitial cells (T-I) were separated and cultured. Cells were treated with increasing concentrations of GM-CSF, then evaluated for CYP17 mRNA and protein expression assays.

Results: After 10 days of treatment with GM-CSF, the number of small preantral and large preantral follicles was significantly increased compared with the control group (P < 0.05). Similarly, treatment with FSH increased the number of small preantral and large preantral follicles (P < 0.05). CD45 expression measured by immunofluorescence was not different in the three groups, indicating that the distribution of leukocytes was unchanged. In addition, CYP17 was increased in the T-I cells both in vivo and in vitro after GM-CSF treatment.

Conclusion: The present results suggest that GM-CSF may play a significant role in follicular development.

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Female
  • Follicle Stimulating Hormone / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology
  • Leukocyte Common Antigens / biosynthesis
  • Microscopy, Fluorescence
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / growth & development*
  • Ovary / drug effects
  • Ovary / metabolism*
  • RNA / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Steroid 17-alpha-Hydroxylase / metabolism
  • Theca Cells / metabolism
  • Time Factors


  • RNA, Messenger
  • RNA
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Follicle Stimulating Hormone
  • Steroid 17-alpha-Hydroxylase
  • Leukocyte Common Antigens