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Hum. Reprod. Advance Access published online on March 11, 2004
Human Reproduction, doi:10.1093/humrep/deh204
© 2004 by European Society of Human Reproduction and Embryology
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Received December 19, 2003
Accepted February 10, 2004

Article

Adrenomedullin and vascular endothelial growth factor production by follicular fluid macrophages and granulosa cells

Juan Balasch 1*, Marta Guimerá 2, Olga Martinez-Pasarell 2, Josefa Ros 3, Juan A. Vanrell 2, and Wladimiro Jiménez 3

1 Institut Clinic of Gynecology, Obstetrics and Neonatology, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Institut Clinic of Gynecology, Obstetrics and Neonatology, Hospital Clinic, C/Casanova 143, 08036 Barcelona, Spain
2 Institut Clinic of Gynecology, Obstetrics and Neonatology, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3 Hormonal Laboratory, Faculty of Medicine-University of Barcelona, Hospital Clinic-Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain

* To whom correspondence should be addressed. E-mail: jbalasch{at}medicina.ub.es.


  Abstract

BACKGROUND: Human follicular fluid contains several substances, such as cytokines and growth factors, which may affect follicular growth and maturation. The present study examines the relative contribution of macrophages and granulosa cells in the production of vascular endothelial growth factor (VEGF) and adrenomedullin in the human ovulatory follicle. METHODS: Both follicular fluid samples and blood samples were obtained at the time of oocyte retrieval following ovarian stimulation from 20 women undergoing IVF treatment because of male infertility. Human follicular fluid macrophages and luteinized granulosa cells were obtained from pooled follicular fluid of individual patients. Accumulation of VEGF and adrenomedullin in the culture medium of the isolated macrophages and human granulosa cells was determined at variable time intervals ranging from 0 to 48 h. Plasma and follicular fluid concentrations of VEGF and adrenomedullin were also measured. RESULTS: The follicular fluid concentrations of VEGF and adrenomedullin were significantly higher than those found in plasma. After 48 h, accumulation of VEGF in the culture medium of follicular fluid macrophages was significantly higher than that released in the culture medium of luteinized granulosa cells. In contrast, the production rate of adrenomedullin by follicular fluid macrophages was similar to that found in granulosa cells. VEGF secreted by follicular fluid macrophages increased progressively within 48 h of cell culture. A similar response pattern was observed with the culture medium of luteinized granulosa cells, but with lower production rates. CONCLUSIONS: This study suggests for the first time that both luteinized granulosa cells and macrophages actively secrete VEGF and adrenomedullin into follicular fluid in the human ovary.

Key words: Key words: adrenomedullin/follicular fluid/luteinized granulosa cells/macrophages/VEGF


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