MicroRNA-185-5p: a marker of brain-sparing in foetuses with late-onset growth restriction

ABSTRACT

To compare the expression of microRNA-185-5p (miR-185-5p) in normal foetuses and in foetuses with late-onset growth restriction (FGR) and to determine the factors influencing this expression. In a prospective study, 40 foetuses (22 of them with late-onset FGR and 18 with normal growth) were scanned with Doppler ultrasound after week 35 and followed until birth. Subsequently, blood samples from umbilical cords were collected after delivery to evaluate the expression of miR-185-5p using real-time qPCR. Finally, multivariable regression analysis was applied to determine the clinical and ultrasonographic factors influencing miR-185-5p expression in both normal and late-onset FGR foetuses. In comparison with normal foetuses, late-onset FGR foetuses expressed upregulation of miR-185-5p (2.26 ± 1.30 versus 1.27 ± 1.03 2^-ddCt, P = 0.011). Multivariable regression analysis confirmed that cerebroplacental ratio (P < 0.05) was the only determinant of this overexpression. FGR foetuses overexpress miR-185-5p in relation to brain-sparing. Future studies will be needed to investigate the role of miR-185 in the management of late-onset FGR.

KEYWORDS:

• MicroRNA-185-5p
• foetal growth
• late-onset foetal growth restriction
• foetal Doppler

Acknowledgments

We would like to thank Patricia Roman Perez (midwife), Dr. Julia Desco (obstetrician) and Dr. Alicia Martinez Varea (obstetrician), for their valuable collaboration in recruiting the patients with FGR. In addition, we would like to thank the midwifery team and the personnel of the maternity operating rooms for their contribution in collecting blood samples.

Authors’ contributions

José Morales-Roselló designed the study, performed the ultrasound examinations, performed part of the statistical analysis and wrote the manuscript.

Eva María García Lopez, José Santiago Ibañez Cabellos and José Luis García Gimenez made the qPCR analysis, supervised the final manuscript and suggested valuable inputs to the text.

Gabriela Loscalzo performed data search and made notable contributions to the final text.

Antonio José Cañada Martínez performed part of the statistical analysis.

Alfredo Perales Marín supervised the manuscript and suggested valuable inputs to the text.

Disclosure statement

José Luis García-Giménez owns stocks in EpiDisease SL (Spin-Off from the Consortium Center for Biomedical Network Research-Spanish Institute of Health Carlos III), an epigenetics company focused on the development of epigenetic biomarkers. Other authors report no conflict of interests.

Data availability

The data that support the findings of this study are available from the corresponding author, JMR, upon reasonable request.

Statement of ethics

Institutional Review Board permission was obtained for this study (Reference 2016/453).

Additional information

Funding

Funds were obtained from iPlacenta project, European Union’s Horizon 2020 Research and Innovation Programme, Marie Skłodowska-Curie grant agreement Number [765274].