Abstract
Research question
Is the blastocyst's idiosyncratic metabolic production of lactate, and creation of
a specialized microenvironment at the implatation site, an important mediator of maternal–fetal
signalling to promote endometrial receptivity and implantation?
Design
Hormonally primed ECC-1 and Ishikawa cells were used to assess functional changes
to the endometrial epithelium after exposure to lactic acid (LA), LA with neutralized
pH (nLA) or acidic pH (pHL). Tight junction integrity (transepithelial resistance [TER]), cellular proliferation
or changes to gene expression by RT-PCR were analysed. The effect of LA on Endometrial
stromal cells decidualization and migratory capacity, and HUVEC endothelial tube formation
and angiogenesis, were also assessed.
Results
Treatment of ECC-1 cells with 2.5 mM (P = 0.0037), 5 mM (P = 0.0044), 7.5 mM and 10 mM (P = 0.003) (P = 0.0021) LA significantly decreased the rate of cellular proliferation while TER
was decreased with exposure to 2.5 mM LA (P = 0.024), 5 mM LA (P = 0.021) and 7.5 mM LA (P = 0.033). Exposure to nLA or pHL had no effect on proliferation or TER. Upregulation of GLUT4 (P = 0.002), GPR81 (P = 0.048), VEGF, SNAI1 (both P < 0.001) and RELA (P = 0.023) mRNA expression was observed after exposure of Ishikawa cells to combined
LA plus pHL. Lactic acid increased the migratory capacity of decidualized stromal cells (P = 0.047) without changing the extent of decidualization. HUVEC tube formation was
significantly increased by 5 mM LA exposure (P = 0.009).
Conclusions
The identification of LA as an important mediator in the maternal–fetal dialogue underpinning
implantation is supported. Further examination of the role of LA within the infertile
or compromised endometrium could improve natural and assisted pregnancy success and
needs further investigation.
KEYWORDS
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Biography
Kathryn Gurner completed her PhD under the supervision of Professor David Gardner and Dr Alexandra Harvey at the University of Melbourne. Her research focuses on understanding both sides of the maternal–fetal dialogue underpinning embryonic development and implantation. She now works as a clinical research embryologist at Melbourne IVF.
Key message
The specialized microenvironment created by the blastocyst, characterized by high lactate and low pH, enhances endometrial remodelling for receptivity and implantation through functional changes to endometrial epithelial, stromal and endothelial cells. Therefore, lactic acid is to be an important signalling molecule underpinning the maternal–fetal dialogue at implantation.
Article info
Publication history
Published online: September 20, 2021
Accepted:
September 10,
2021
Received in revised form:
September 6,
2021
Received:
June 12,
2021
Declaration: The authors report no financial or commercial conflicts of interest.Identification
Copyright
© 2021 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
