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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Developmental Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1386309
This article is part of the Research Topic Maternal-Fetal interface: new insight in placenta research Volume II View all 3 articles

The Effects of Leptin on Human Cytotrophoblast Invasion are Gestational Age and Dose-Dependent

Provisionally accepted
Kristen K. Rumer Kristen K. Rumer 1,2Shilpi Sehgal Shilpi Sehgal 2Kevin P. Bogart Kevin P. Bogart 1Anita Kramer Anita Kramer 1Virginia D. Winn Virginia D. Winn 1,3*
  • 1 Department of Obstetrics and Gynecology, School of Medicine, University of Colorado, Aurora,, Colorado, United States
  • 2 Department of Obstetrics and Gynecology, School of Medicine, Stanford University, Stanford, California, United States
  • 3 School of Medicine, Stanford University, Stanford, California, United States

The final, formatted version of the article will be published soon.

    Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized. Leptin is overexpressed in the placentas from preeclamptic (PE) pregnancies. PE can result from the impaired invasion of fetal placental cells, cytotrophoblasts (CTBs), into the maternal decidua. We hypothesized that elevated leptin levels would impair human CTB invasion. The effects of leptin on the invasion of human CTBs were evaluated using HTR-8/SVneo cells, primary CTBs, and placental villous explants. We found that, prior to 8 weeks gestation, leptin promoted CTB invasion in the explant model. After 11 weeks gestation in explants, primary CTBs and in HTR-8/SVneo cells, leptin promoted invasion at moderate but not at high concentrations. These data suggest that the excess placental leptin observed in PE may cause impaired CTB invasion as a second-trimester defect. Further, the expression of leptin receptors was characterized. Leptin receptor expression did not vary over gestation, however, STAT, PI3K and MAPK pathways showed different signaling in response to varied leptin doses.Leptin's differential effect on trophoblast invasion may explain the role of hyperleptinemia in preeclampsia pathogenesis.

    Keywords: invasion, Leptin, leptin receptor, Placenta, Preeclampsia, trophoblast

    Received: 15 Feb 2024; Accepted: 08 May 2024.

    Copyright: © 2024 Rumer, Sehgal, Bogart, Kramer and Winn. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Virginia D. Winn, School of Medicine, Stanford University, Stanford, 94305-5101, California, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.