Matrix metalloproteinase 15 plays a pivotal role in human first trimester cytotrophoblast invasion and is not altered by maternal obesity

摘要

Adequate anchoring of the placenta in the uterus through invasion of first trimester cytotrophoblasts (CTB) is required for a successful pregnancy. This process is mediated by matrix metalloproteinases (MMPs) and regulated by the maternal environment. Obesity is known to alter the intrauterine milieu and has been related to impaired invasion. We hypothesized that placental MMP15, a novel membrane‐type MMP, is involved in CTB invasion and regulated by maternal obesity in early pregnancy. Thus, in this study MMP15 was immunolocalized to invasive extravillous and interstitial CTB. MMP15 silencing in chorionic villous explants using two different siRNAs reduced trophoblast outgrowth length (?35%, P ?≤?.001 and ?26%, P ?&?.05) and area (?43%, P ?≤?.001 and ?36%, P ?≤?.01) without altering trophoblast proliferation or apoptosis. Short‐term treatment of primary first trimester trophoblasts with IL‐6 (10?ng/mL), interleukin 10 (IL‐10) (50?ng/mL), and tumor necrosis factor α (TNF‐α) (10?ng/mL) did not affect MMP15 protein levels. Likewise, MMP15 mRNA and protein levels were unaltered between human first trimester placentas from control pregnancies vs those complicated with maternal obesity. Overall, our results suggest that the role of MMP15 in placental development and function in early pregnancy is limited to CTB invasion without being affected by short‐ and long‐term inflammation.