The Pivotal Role of the Placenta in Normal and Pathological Pregnancies: A Focus on Preeclampsia, Fetal Growth Restriction, and Maternal Chronic Venous Disease

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Feb 15

PMID 35159377

Authors

Miguel A Ortega

Oscar Fraile-Martinez

Cielo Garcia-Montero

Miguel A Saez

Miguel Angel Alvarez-Mon

Diego Torres-Carranza

Melchor Alvarez-Mon

Julia Bujan

Natalio Garcia-Honduvilla

Coral Bravo

Luis G Guijarro

Juan A De Leon-Luis

Affiliations

Soon will be listed here.

Abstract

The placenta is a central structure in pregnancy and has pleiotropic functions. This organ grows incredibly rapidly during this period, acting as a mastermind behind different fetal and maternal processes. The relevance of the placenta extends far beyond the pregnancy, being crucial for fetal programming before birth. Having integrative knowledge of this maternofetal structure helps significantly in understanding the development of pregnancy either in a proper or pathophysiological context. Thus, the aim of this review is to summarize the main features of the placenta, with a special focus on its early development, cytoarchitecture, immunology, and functions in non-pathological conditions. In contraposition, the role of the placenta is examined in preeclampsia, a worrisome hypertensive disorder of pregnancy, in order to describe the pathophysiological implications of the placenta in this disease. Likewise, dysfunction of the placenta in fetal growth restriction, a major consequence of preeclampsia, is also discussed, emphasizing the potential clinical strategies derived. Finally, the emerging role of the placenta in maternal chronic venous disease either as a causative agent or as a consequence of the disease is equally treated.

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References

Maia E Holanda Moura S, Marques Lopes L, Murthi P, da Silva Costa F . Prevention of preeclampsia. J Pregnancy. 2013; 2012:435090. PMC: 3534321. DOI: 10.1155/2012/435090. View

Ortega M, Saez M, Sainz F, Fraile-Martinez O, Garcia-Gallego S, Pekarek L . Lipidomic profiling of chorionic villi in the placentas of women with chronic venous disease. Int J Med Sci. 2020; 17(17):2790-2798. PMC: 7645335. DOI: 10.7150/ijms.49236. View

Garcia-Honduvilla N, Asunsolo A, Ortega M, Sainz F, Leal J, Lopez-Hervas P . Increase and Redistribution of Sex Hormone Receptors in Premenopausal Women Are Associated with Varicose Vein Remodelling. Oxid Med Cell Longev. 2018; 2018:3974026. PMC: 6140006. DOI: 10.1155/2018/3974026. View

Hoo R, Nakimuli A, Vento-Tormo R . Innate Immune Mechanisms to Protect Against Infection at the Human Decidual-Placental Interface. Front Immunol. 2020; 11:2070. PMC: 7511589. DOI: 10.3389/fimmu.2020.02070. View

Cetin I, Mazzocco M, Giardini V, Cardellicchio M, Calabrese S, Algeri P . PlGF in a clinical setting of pregnancies at risk of preeclampsia and/or intrauterine growth restriction. J Matern Fetal Neonatal Med. 2016; 30(2):144-149. DOI: 10.3109/14767058.2016.1168800. View

Barapatre N, Haeussner E, Grynspan D, Schmitz C, von Koch F, Frank H . The Density of Cell Nuclei at the Materno-Fetal Exchange Barrier is Sexually Dimorphic in Normal Placentas, but not in IUGR. Sci Rep. 2019; 9(1):2359. PMC: 6382753. DOI: 10.1038/s41598-019-38739-9. View

Romo A, Carceller R, Tobajas J . Intrauterine growth retardation (IUGR): epidemiology and etiology. Pediatr Endocrinol Rev. 2009; 6 Suppl 3:332-6. View

Gu Y, Lewis D, Wang Y . Placental productions and expressions of soluble endoglin, soluble fms-like tyrosine kinase receptor-1, and placental growth factor in normal and preeclamptic pregnancies. J Clin Endocrinol Metab. 2007; 93(1):260-6. PMC: 2190747. DOI: 10.1210/jc.2007-1550. View

Beune I, Bloomfield F, Ganzevoort W, Embleton N, Rozance P, van Wassenaer-Leemhuis A . Consensus Based Definition of Growth Restriction in the Newborn. J Pediatr. 2018; 196:71-76.e1. DOI: 10.1016/j.jpeds.2017.12.059. View

10.

Ortega M, Asunsolo A, Fraile-Martinez O, Sainz F, Saez M, Bravo C . An increase in elastogenic components in the placental villi of women with chronic venous disease during pregnancy is associated with decreased EGFL7 expression level. Mol Med Rep. 2021; 24(2). PMC: 8188638. DOI: 10.3892/mmr.2021.12195. View

11.

Bakrania B, George E, Granger J . Animal models of preeclampsia: investigating pathophysiology and therapeutic targets. Am J Obstet Gynecol. 2021; 226(2S):S973-S987. PMC: 8141071. DOI: 10.1016/j.ajog.2020.10.025. View

12.

Sovio U, White I, Dacey A, Pasupathy D, Smith G . Screening for fetal growth restriction with universal third trimester ultrasonography in nulliparous women in the Pregnancy Outcome Prediction (POP) study: a prospective cohort study. Lancet. 2015; 386(10008):2089-2097. PMC: 4655320. DOI: 10.1016/S0140-6736(15)00131-2. View

13.

Predoi C, Grigoriu C, Vladescu R, Mihart A . Placental damages in preeclampsia - from ultrasound images to histopathological findings. J Med Life. 2015; 8 Spec Issue:62-5. PMC: 4564041. View

14.

Fleiss B, Wong F, Brownfoot F, Shearer I, Baud O, Walker D . Knowledge Gaps and Emerging Research Areas in Intrauterine Growth Restriction-Associated Brain Injury. Front Endocrinol (Lausanne). 2019; 10:188. PMC: 6449431. DOI: 10.3389/fendo.2019.00188. View

15.

Fruscalzo A, Cividino A, Rossetti E, Maurigh A, Londero A, Driul L . First trimester PAPP-A serum levels and long-term metabolic outcome of mothers and their offspring. Sci Rep. 2020; 10(1):5131. PMC: 7083850. DOI: 10.1038/s41598-020-61830-5. View

16.

Plotkin S, Wang D, Oualim A, Diamond D, Kotton C, Mossman S . The Status of Vaccine Development Against the Human Cytomegalovirus. J Infect Dis. 2020; 221(Suppl 1):S113-S122. PMC: 7057802. DOI: 10.1093/infdis/jiz447. View

17.

Herzog E, Eggink A, Reijnierse A, Kerkhof M, de Krijger R, Roks A . Impact of early- and late-onset preeclampsia on features of placental and newborn vascular health. Placenta. 2016; 49:72-79. DOI: 10.1016/j.placenta.2016.11.014. View

18.

Tilburgs T, Strominger J . CD8+ effector T cells at the fetal-maternal interface, balancing fetal tolerance and antiviral immunity. Am J Reprod Immunol. 2013; 69(4):395-407. PMC: 3711858. DOI: 10.1111/aji.12094. View

19.

Birdir C, Droste L, Fox L, Frank M, Fryze J, Enekwe A . Predictive value of sFlt-1, PlGF, sFlt-1/PlGF ratio and PAPP-A for late-onset preeclampsia and IUGR between 32 and 37 weeks of pregnancy. Pregnancy Hypertens. 2018; 12:124-128. DOI: 10.1016/j.preghy.2018.04.010. View

20.

Audette M, Kingdom J . Screening for fetal growth restriction and placental insufficiency. Semin Fetal Neonatal Med. 2017; 23(2):119-125. DOI: 10.1016/j.siny.2017.11.004. View