Periconceptional Ethanol Consumption Alters Collagens and Metalloproteinase-9 Expression in CF-1 Murine Implantation Sites at Midgestation

COLL TA; FONTANA V; FAVARO R; IGLESIAS A; PEREZ TITO, L; CALVO JC; ZORN T; CEBRAL E

Santiago de Chile

Congreso; IFPA Meeting 2010 Placenta - Fetus and Placenta: a perfect harmony; 2010

International Federation of Placenta Associations

Periconceptional alcohol ingestion causes organogenic embryo anomalies, growth restriction and increased early miscarriages. The matrix metalloproteinase 9 (MMP-9) cleaves type IV and V collagens, playing a role in decidualization, angiogenesis, trophoblastic migration and its invasion into the decidua. Objective: To evaluate if periconceptional ethanol ingestion alters the distribution and deposition of collagen types I, III, IV and V, and MMP-9 expression and activity in vascular mesometrial decidua (VMD) and trophoblastic (T) tissues when organogenesis is occuring . Methods: Adult CF-1 female mice were treated (TG) with 10% ethanol in drinking water for 17 days previously and up to day 10 of gestation, and they were compared to control group (CG). Implantation sites were processed for picrosirius staining for fibrillar collagens, and immunohistochemistry for I, III, IV, V collagens and MMP-9. Decidual tissues (D) were dissected to perform western blotting for MMP-9 and conditioned media from D 24 h-culture was used to zymograms. Results: In VMD-CG picrosirius staining was observed as a defined and continuous line underlying the region of basal membrane of the endothelium of blood vessel, whereas in the VMD-TG it was discontinuous and faintly stained. Collagens I and III had similar immunostaining in the VMD-CG and VMD-TG, whereas the immunoreaction for type  IV and V collagens was increased in VMD-TG. A slight immunoreaction for MMP-9 was detected in both VMD-CG and T-CG. However, the immunoreactivity was significantly reduced in VMD-TG and T-TG. In D-TG, the MMP-9 expression (immunoblotting) and zymographic analysis for the active form in conditioned medium was significantly decreased vs D-CG. Discussion: Periconceptional alcohol ingestion, alters collagens deposition and collagen fibrils arrangement in the mouse pregnant endometrium, which was correlated with reduced MMP-9 expression and activity. These effects may be related to early anomalies in decidual-placental development and increased miscarriage due to maternal alcohol consumption.