Aquaporin 3 promotes human extravillous trophoblast migration and invasion

Yingqi Nong,Qianyu Zhang,Xiqian Zhang,Ye Chen,Lin Fan,Fenghua Liu,Wenjuan Liu,Shifen Li,Qianwen Huang

doi:10.1186/s12958-021-00726-z

Abstract

ProblemDoes aquaporin 3 (AQP3) affect the migration and invasion of human extravillous trophoblast (HTR8/Svneo) cells?Method of studyA lentivirus infection system was used to construct stable cell lines with either AQP3 knockdown or overexpression. RT-PCR and western blotting were used to verify the efficiencies of AQP3 knockdown or overexpression in HTR8/Svneo cells at mRNA and protein levels, respectively. Cell Counting Kit-8 and flow cytometry assays were used to detect the influence of AQP3 knockdown or overexpression on proliferation and apoptosis of HTR8/Svneo cells. In addition, wound healing and Transwell invasion assays were used to detect the effects of AQP3 knockdown or overexpression on migration and invasion capabilities of HTR8/Svneo cells. An Agilent gene chip was used to screen for significant differentially expressed genes after AQP3 knockdown. Finally, mechanisms by which AQP3 influences the migration and invasion of HTR8/Svneo cells were explored using bioinformatic analysis.ResultsCompared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after AQP3 knockdown, and significantly increased after AQP3 overexpression. Subsequent bioinformatic analysis of gene chip expression profiles indicated downregulation of genes related to adhesion such as PDGF-B, as well as signaling pathways (such as PIK3/AKT, NF-κB, and TNF) after AQP3 knockdown.ConclusionsAQP3 could significantly promote migration and invasion capabilities of human extravillous trophoblasts, it may mediate embryo invasion and adhesion to endometrium by regulating PDGF-B, PIK3/AKT signaling pathways, although this requires further verification.

Highlights

Recurrent implantation failure (RIF) is one of the bottlenecks of in vitro fertilization-embryo transfer and its derivative techniques
Compared with controls, migration and invasion capabilities of HTR8/Svneo cells were significantly reduced after aquaporin 3 (AQP3) knockdown, and significantly increased after AQP3 overexpression
It has been shown that invasion of trophoblasts into the endometrium is similar to the metastasis of malignant tumors [6], as both involve cell invasion

Summary

Introduction

Recurrent implantation failure (RIF) is one of the bottlenecks of in vitro fertilization-embryo transfer and its derivative techniques. There is no uniform definition on RIF It is widely accepted as a diagnosis criteria which include an age less than 40 years and failure to achieve a clinical pregnancy after transfer. Nong et al Reproductive Biology and Endocrinology (2021) 19:49 implantation includes localization, adhesion, and invasion of the maternal endometrium until embedment into the matrix. This behavior of the embryo invading the endometrium at a specific time and space is the primitive motive for embryo implantation. Migration speed can be controlled by osmotic pressure in extracellular medium This means that high osmotic pressure accelerates migration, while low pressure slows down migration. AQPs play a critical role for compliance with the acceleration of intracellular and extracellular osmotic pressure changes, as well as rapid changes of cellular morphology [10, 11]

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