IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
artículos
Título:
Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF),
Autor/es:
LUCHETTI C.; MIKO E.; SZEKERES J; PAZ D.A.; MOTTA A.
Revista:
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Editorial:
Elsevier
Referencias:
Lugar: Paris Francia; Año: 2008 vol. 111 p. 200 - 207
ISSN:
0960-0760
Resumen:
Abstract: The present study examined the mechanism by which metformin (N, N´, dimethybiguanide)
prevents embryonic resorption induced in mice by dehydroepiandrosterone (DHEA). Treatment with DHEA
(60 mg/Kg, sc 24 and 48 h post implantation) induces embryo resorption of early pregnant BALB/c mice
while simultaneous treatment with metformin (240 mg/Kg, oral 24 and 48 h post implantation) prevents it.
During pregnancy progesterone-induced blocking factor (PIBF) modulates prostaglandins (PGs) and
cytokine production. These findings prompted us to investigate the effect of DHEA and metformin on both
PIBF and cyclooxygenase 2 (COX2) expressions at the implantation sites, as well as cytokine production.
PIBF and COX2 expression were detected by immunohistochemistry from DHEA and DHEA+ metformin
treated 8 days-pregnant mice and serum cytokine levels of these animals were determined by ELISA. DHEA
treatment both abolished PIBF expression and increased COX2 expression. Embryo resorption correlates
with the lack of PIBF expression, diminished IL-6 levels and increased IL-2 concentration while metformin
was able to reverse the effect of DHEA on both PIBF and COX2 expression and IL-6 levels. We concluded
that hyperandrogenization induces embryo resorption in early pregnancy diminishing PIBF in implantation
sites, having a pro-inflammatory effect. Metformin is able to prevent such effects.