Estrogen and progesterone signaling modulate extravillous trophoblast function

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B180
Abstract ID: 4891

Presenting Author:
Adrian D Kocinski , Research Assistant 2 at Case Western Reserve Univ. Sch. of Med.

Abstract:

Healthy pregnancies depend on a complex interplay of reproductive hormones including 17β-estradiol (estrogen, “E2”) and progesterone (“P4”). E2 and P4 are synthesized by extravillous trophoblast (EVT) cells at the maternal-fetal interface and coordinate tissue-level changes including decidualization and maintenance of a tolerogenic immune state. Reductions in E2 or P4 bioavailability or in signaling downstream of E2 and P4 receptors contributes to pregnancy complications such as preterm birth.

Although EVTs are established sources of E2 and P4 in vivo, whether they can respond to hormones represents a significant knowledge gap. Here, we tested the hypothesis that locally-synthesized E2 and P4 directly regulate the immunomodulatory functions of EVTs. We observed that primary EVTs (isolated from human term placentas) and EVT-like cell lines (derived from primary EVTs) express nuclear and membrane receptors for E2 and P4, suggesting that they can respond to hormones. Using our EVT-like cell lines, we found that inhibition of nuclear E2 and P4 receptors alters expression of trophoblast functional genes (i.e. CD276) and proinflammatory cytokines (i.e. TNF-α and IL-6). Collectively, these data suggest that EVTs are targets of autocrine E2 and P4 signaling in vivo. Future studies will continue to investigate the mechanisms by which steroid hormones regulate EVT function, contributing to the balance between inflammation and tolerance at the maternal-fetal interface.