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Hum. Reprod. Advance Access originally published online on June 15, 2005
Human Reproduction 2005 20(10):2749-2756; doi:10.1093/humrep/dei123
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© The Author 2005. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

Reproductive biology

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

Hongbo Wang1,3, Yan Wen2, Mary Lake Polan2, Robert Boostanfar1, Michael Feinman1 and Barry Behr2

1 Huntington Reproductive Center, 1220 La Venta Drive, Westlake Village, CA 91361 and 2 Department of OB/GYN, Stanford University, Stanford, CA 94305, USA

3 To whom correspondence should be addressed. E-mail: whbdf{at}yahoo.com

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.

Key words: CD45/CYP17/follicular development/GM-CSF/in vivo


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