Effects of adiponectin on human trophoblast invasion

Abstract

Adiponectin is an adipokine with insulin-sensitizing, antiinflammatory, anti-atherogenic, and anti-proliferative effects. The expression of specific adiponectin receptors in the placenta and in the endometrium suggests a role for this cytokine in placental development, but this role has not yet been elucidated. The invasion of trophoblast cells during the first trimester of pregnancy being crucial to placentation process, we have studied adiponectin effects on human trophoblast invasive capacities. We found that adiponectin stimulated human trophoblast cell migration in HTR-8/SVneo cells in a dose-independent manner. In addition, adiponectin also significantly enhanced invasion of HTR-8/SVneo cells and of human extravillous trophoblast from first trimester placenta. These pro-invasive effects of adiponectin in human trophoblasts seem to be mediated in part via increased matrix metalloproteinases (MMP2 and MMP9) activities and via repression of TIMP2 mRNA expression. Our results suggest that adiponectin could be a positive regulator of the early invasion process by modulating the MMP/TIMP balance. Moreover, these results provide an insight into the role of adiponectin in pathological conditions characterized by insufficient or excessive trophoblast invasion.

Adiponectin limits differentiation and trophoblast invasion in human endometrial cells

“…In parallel, we performed Matrigel Transwell invasion assays with the HTR-8/SVneo cells in the presence of control medium supplemented or not with adiponectin (25 ng/mL and 250 ng/mL). As previously described by our laboratory, these experiments confirmed that adiponectin (250 ng/mL) enhanced trophoblast invasion (+23%) (Benaitreau et al 2010a). …”

“…A growing body of evidence has highlighted adiponectin role in the establishment of a functional placenta (Benaitreau et al 2010b). Our laboratory has shown that adiponectin promotes human trophoblast invasion by enhancing MMP-2,-9 activities and downregulating TIMP-2 mRNA expression (Benaitreau et al 2010a).…”

“…It is now established that adiponectin is not produced by human trophoblastic cells but seems to be expressed in human endometrium (Takemura et al 2006, Benaitreau et al 2010a, Dos Santos et al 2012. ADIPOR1 and ADIPOR2 are expressed in human placenta and endometrium (Takemura et al 2006, Benaitreau et al 2009.…”

CpG Oligodeoxynucleotides Downregulate Placental Adiponectin and Increase Embryo Loss in Non‐Obese Diabetic Mice

“…While the presence of syncytiotrophoblast adiponectin expression has been previously debated,39, 40 the present study demonstrated adiponectin expression in both syncytiotrophoblasts and decidual glands. In the in vitro model cell experiments, we also found that adiponectin was expressed in syncytial BeWo cells.…”

“…In the current study, ODN 2006 impaired the syncytialization of BeWo cells, but neither knockdown nor overexpression of adiponectin could neutralize this effect, indicating that while it can promote trophoblast syncytialization, adiponectin cannot rescue impairment of syncytialization caused by CpG ODNs or bacterial infection. Furthermore, in addition to supporting syncytialization, adiponectin can also promote the human trophoblast migration 40. However, little is known about the effect of adiponectin on trophoblast migration under infectious conditions.…”