The role of placental kisspeptin in trophoblast invasion and migration: an assessment in Kiss1r knockout mice, BeWo cell lines and human term placenta

E. N. Panting; J. H. Weight; J. A. Sartori; D. A. Coall; J. T. Smith

doi:10.1071/RD23230

RESEARCH ARTICLE (Open Access)

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The role of placental kisspeptin in trophoblast invasion and migration: an assessment in Kiss1r knockout mice, BeWo cell lines and human term placenta

E. N. Panting ^A ^# , J. H. Weight ^A ^# , J. A. Sartori

^B , D. A. Coall

^B and J. T. Smith

^A ^*

+ Author Affiliations

- Author Affiliations

^A School of Human Sciences, The University of Western Australia, Perth, WA 6009, Australia.

^B School of Medical and Health Sciences, Edith Cowan University, Joondalup, WA 6027, Australia.

^* Correspondence to: jeremy.smith@uwa.edu.au

^# These authors contributed equally to this paper

Handling Editor: Ellen Menkhorst

Reproduction, Fertility and Development 36, RD23230 https://doi.org/10.1071/RD23230

Submitted: 18 January 2024 Accepted: 17 June 2024 Published online: 8 July 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing. This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND)

Abstract

Context

There is mounting evidence implicating kisspeptin signalling in placental development and function.

Aims

This study aimed to elucidate kisspeptin’s role in trophoblast invasion and migration using three experimental models.

Methods

First, we examined the mouse fetus and placenta in a kisspeptin receptor (Kiss1r) knockout (KO) model. Fetal/placental weights and gene expression (quantitative polymerase chain reaction) were assessed. Second, we determined kisspeptin effects on a human trophoblast (BeWo) cell line in vitro. Third, we examined KISS1 and KISS1R gene expression in human placenta from term and pre-term pregnancies.

Key results

No difference was found in fetal or placental weight between Kiss1r KO and wildtype mice. However, expression of the trophoblast invasion marker, Mmp2 mRNA, was greater in the placental labyrinth zone of Kiss1r KO mice. BeWo cell models of villus cytotrophoblast and syncytiotrophoblast cells exhibited kisspeptin protein expression, with greater expression in syncytiotrophoblast, consistent with KISS1 mRNA. Kisspeptin treatment inhibited the migratory potential of cytotrophoblast-like cells. Finally, while no difference was seen in KISS1 and KISS1R mRNA between term and pre-term placentas, we saw a difference in the relative expression of each gene pre-term. We also observed a positive correlation between KISS1 expression and maternal body mass index.

Conclusions

Our results indicate that kisspeptin may inhibit trophoblast invasion.

Implications

Further investigation is required to clarify specific regulatory mechanisms.

Keywords: GPR54, invasion, Kiss1, kisspeptin, migration, placenta, preeclampsia, pregnancy.

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