Women have a lifetime rate of major depression 1.7 to 2.7 times greater than that for men, with increased risk for the first onset of major depression during childbearing years. Recently, there has been increased use of serotonin norepinephrine reuptake inhibitors (SNRIs) as an alternative to selective serotonin reuptake inhibitors (SSRIs) higher relative success rates in the treatment of depression. This project aims to investigate the molecular mechanisms underlying an observation of reduced growth in offspring exposed to venlafaxine, an SNRI antidepressant. The HTR-8/SVneo cell line is a transformed extravillous trophoblast cell line used to study trophoblast functions including cell proliferation, migration, invasion, and angiogenesis. Angiogenesis is a key factor in the placentation process, involving several growth factors such as vascular endothelial growth factor (VEGF) and angiopoietin-like protein 4 (ANGPTL4). A tube formation assay was performed on matrigel in order to evaluate the angiogenic response of HTR-8/SVneo cells in the presence of venlafaxine (0.05, 0.25, or 1.0 mM). The results demonstrate that venlafaxine has an inhibitory effect on tube length, segment length, and number of junctions formed by HTR-8/SVneo cells. In addition, the study investigated the effects of venlafaxine on the levels of gene involved in angiogenesis in these cells. Gene expression was determined after incubating these cells with different concentrations of venlafaxine for 24 h using real-time qRT-PCR. A VEGF receptor, VEGFR2, was induced and may be associated with decreased levels of bioavailable VEGF. Altogether these data indicate that venlafaxine may potently influence the placentation process by decreasing tube formation.