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Abstract:

The present study examined the mechanism by which metformin (N,N′-dimethylbiguanide) prevents embryonic resorption induced in mice by dehydroepiandrosterone (DHEA). Treatment with DHEA (60 mg/kg, s.c. 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. © 2008 Elsevier Ltd. All rights reserved.

Registro:

Documento: Artículo
Título:Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice
Autor:Luchetti, C.G.; Mikó, E.; Szekeres-Bartho, J.; Paz, D.A.; Motta, A.B.
Filiación:Laboratorio de Fisiopatología Ovárica, Centro de Estudios Farmacológicos y Botánicos (CEFYBO), Consejo de Investigaciones Científicas y Tecnológicas, Paraguay 2155 Buenos Aires, Argentina
Facultad de Medicina, Departamento de Farmacología, Buenos Aires, Argentina
Department of Medical Microbiology and Immunology, Pecs University, Medical School, 12 Szigeti Street, H-7624 Pecs, Hungary
Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina
Palabras clave:Cytokines; Dehydroepiandrosterone; Metformin; PIBF; Pregnancy; Progesterone; cyclooxygenase 2; cytokine; gamma interferon; interleukin 2; interleukin 4; interleukin 6; metformin; placenta protein; prasterone; progesterone; progesterone induced blocking factor protein; prostaglandin; animal experiment; animal model; animal tissue; article; blocking factor; controlled study; cytokine production; drug mechanism; embryo resorption; enzyme linked immunosorbent assay; female; immunohistochemistry; mouse; nonhuman; protein blood level; protein expression; Animals; Cyclooxygenase 2; Cytokines; Dehydroepiandrosterone; Embryo Implantation; Embryo Loss; Embryo, Mammalian; Female; Hypoglycemic Agents; Male; Metformin; Mice; Mice, Inbred BALB C; Pregnancy; Pregnancy Proteins; Pregnancy, Animal; Suppressor Factors, Immunologic; Animalia; Mus
Año:2008
Volumen:111
Número:3-5
Página de inicio:200
Página de fin:207
DOI: http://dx.doi.org/10.1016/j.jsbmb.2008.06.007
Título revista:Journal of Steroid Biochemistry and Molecular Biology
Título revista abreviado:J. Steroid Biochem. Mol. Biol.
ISSN:09600760
CODEN:JSBBE
CAS:gamma interferon, 82115-62-6; interleukin 2, 85898-30-2; metformin, 1115-70-4, 657-24-9; prasterone, 53-43-0; progesterone, 57-83-0; Cyclooxygenase 2, EC 1.14.99.1; Cytokines; Dehydroepiandrosterone, 53-43-0; Hypoglycemic Agents; Metformin, 657-24-9; Pibf1 protein, mouse; Pregnancy Proteins; Suppressor Factors, Immunologic
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_09600760_v111_n3-5_p200_Luchetti

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Citas:

---------- APA ----------
Luchetti, C.G., Mikó, E., Szekeres-Bartho, J., Paz, D.A. & Motta, A.B. (2008) . Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice. Journal of Steroid Biochemistry and Molecular Biology, 111(3-5), 200-207.
http://dx.doi.org/10.1016/j.jsbmb.2008.06.007
---------- CHICAGO ----------
Luchetti, C.G., Mikó, E., Szekeres-Bartho, J., Paz, D.A., Motta, A.B. "Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice" . Journal of Steroid Biochemistry and Molecular Biology 111, no. 3-5 (2008) : 200-207.
http://dx.doi.org/10.1016/j.jsbmb.2008.06.007
---------- MLA ----------
Luchetti, C.G., Mikó, E., Szekeres-Bartho, J., Paz, D.A., Motta, A.B. "Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice" . Journal of Steroid Biochemistry and Molecular Biology, vol. 111, no. 3-5, 2008, pp. 200-207.
http://dx.doi.org/10.1016/j.jsbmb.2008.06.007
---------- VANCOUVER ----------
Luchetti, C.G., Mikó, E., Szekeres-Bartho, J., Paz, D.A., Motta, A.B. Dehydroepiandrosterone and metformin modulate progesterone-induced blocking factor (PIBF), cyclooxygenase 2 (COX2) and cytokines in early pregnant mice. J. Steroid Biochem. Mol. Biol. 2008;111(3-5):200-207.
http://dx.doi.org/10.1016/j.jsbmb.2008.06.007