Placental Growth Factor: Physiology and What Research Reports

This page is for educational purposes only and is not medical advice; consult a licensed physician for any question about health, pregnancy, or medication. It summarises what published studies have reported about placental growth factor and does not describe any protocol, product, or course of action.

What Placental Growth Factor Is

Placental growth factor (PlGF), encoded by the PGF gene, is a secreted glycoprotein belonging to the vascular endothelial growth factor (VEGF) family. It was originally identified in placental tissue, which gave the molecule its name, but it is not exclusive to pregnancy. Unlike VEGF-A, which engages both VEGF receptor-1 and receptor-2, PlGF binds principally to VEGF receptor-1 (VEGFR-1 / Flt-1) and to the co-receptors neuropilin-1 and neuropilin-2. Expression of PlGF alongside neuropilin-1 and neuropilin-2 was examined directly in human primary pterygium tissue in a 2024 ophthalmology report, which described the three molecules as a co-expressed signalling set in that vascularised conjunctival lesion (PMID 37878035).

Because PlGF shares receptor space with VEGF, it is usually discussed in the context of angiogenesis — the growth and remodelling of blood vessels — and of endothelial function, the behaviour of the cell layer lining vessels. A soluble fragment of its receptor, soluble Flt-1 (sFlt-1), circulates in blood and binds PlGF, so free PlGF concentrations reflect both how much is produced and how much is being sequestered.

Where It Is Produced and What It Appears to Do

The placenta, and specifically trophoblast tissue, is the dominant source during pregnancy. PlGF is also expressed by vascular endothelium, heart, lung, thyroid, skeletal muscle, and adipose tissue. In a laboratory model of the maternal–fetal interface, researchers applied PlGF to trophoblast and endothelial cell co-cultures and reported effects on how those two cell types interacted in vitro, work that was framed as relevant to how spiral arteries are remodelled in early pregnancy (PMID 32016802).

Outside reproduction, a 2024 study in Metabolism reported that PlGF deficiency initiated obesity- and aging-associated features of metabolic syndrome in its experimental model, positioning the protein as a participant in adipose tissue vascularisation and metabolic regulation rather than a purely placental factor (PMID 39173826).

How It Differs from VEGF-A

• Receptor preference: PlGF signals mainly through VEGFR-1 and neuropilins, and neuropilin co-expression with PlGF has been documented in human vascularised tissue (PMID 37878035).
• Context: reviews of the pregnancy literature have described PlGF as more prominent in pathological and adaptive vessel growth than in routine developmental angiogenesis (PMID 29115294).
• Measurability: PlGF is stable enough in plasma and serum to be used as a repeated-measures biomarker across pregnancy (PMID 38151219).

How PlGF Is Measured and Studied

Three broad approaches recur in the literature:

1. Circulating protein. Immunoassays on maternal serum or plasma generate concentrations that can be tracked longitudinally; one analysis from the Aspirin for Evidence-Based Preeclampsia Prevention trial reported how maternal serum PlGF and pregnancy-associated plasma protein A trajectories across pregnancy differed with aspirin allocation (PMID 38151219).
2. Tissue mRNA and protein expression. A 2017 study compared PlGF mRNA expression in preeclamptic and normotensive placental tissue and reported differences between the groups (PMID 28580450).
3. Cell and animal models. Loss-of-function models and cell co-culture systems test whether PlGF is causally involved rather than merely correlated, as in the PlGF-deficiency metabolic work (PMID 39173826) and the trophoblast–endothelial co-culture experiments (PMID 32016802).

What the Literature Reports

Pregnancy and Preeclampsia

Preeclampsia is where PlGF has been studied most heavily. A review of the field described low circulating PlGF as a feature of preeclampsia and discussed its use in assessment of the disorder (PMID 29115294). At the tissue level, researchers reported altered PlGF mRNA expression in preeclamptic placentas compared with controls (PMID 28580450). A 2022 obstetric cohort reported that PlGF level correlated with intrapartum fetal heart rate findings, extending the biomarker beyond diagnosis into labour monitoring research (PMID 35300623).

Environmental epidemiology has also used PlGF as an intermediate variable: a 2025 analysis reported that maternal PlGF mediated part of the association between PM_2.5 and its chemical constituents and adverse pregnancy outcomes (PMID 40840043).

Cardiometabolic and Vascular Biology

The 2024 Metabolism study reported that removing PlGF signalling was sufficient to initiate obesity- and aging-associated metabolic syndrome features in its model system, suggesting a maintenance role for the protein in metabolic tissue vasculature (PMID 39173826).

Brain Imaging and Cognition

Two 2025 reports examined plasma PlGF in neurodegenerative contexts. One reported an association between plasma PlGF and white matter hyperintensities — an MRI marker of small-vessel disease — in Alzheimer's disease (PMID 41154596). Another described plasma PlGF as a susceptibility biomarker for longitudinal cognitive change (PMID 41388837). Both were observational biomarker analyses rather than interventions.

Cancer Biology

In tumour research, a 2015 mechanistic study reported that PlGF promoted metastasis of ovarian cancer cells through a miR-543-regulated MMP7 pathway (PMID 26402225). Separately, PlGF and its neuropilin co-receptors were detected in primary pterygium, a benign but vascularised ocular growth (PMID 37878035).

Acute Illness

During the COVID-19 pandemic, researchers reported that plasma PlGF level predicted COVID-19 severity and in-hospital mortality in their cohort, consistent with the protein behaving as a marker of endothelial disturbance in acute systemic illness (PMID 33830623).

Directions of Change Reported Across Contexts

Safety and Risk Signals in the Literature: What Studies Report

PlGF is an endogenous protein studied as a biomarker and a signalling molecule, not a supplement or an approved therapeutic, so the literature gathered here contains no administration safety data in humans. The risk signals that do appear are biological rather than pharmacological. On one side, a mechanistic study reported that PlGF promoted ovarian cancer metastasis through MMP7 regulation, meaning higher PlGF activity was not framed as uniformly favourable (PMID 26402225). On the other, PlGF deficiency was reported to initiate metabolic syndrome features in an experimental model (PMID 39173826), and elevated plasma PlGF was reported to track with worse outcomes in hospitalised COVID-19 (PMID 33830623). Readers encountering the term should note that direction of change means different things in different tissues and diseases.

Why the Term Appears in Peptide-Adjacent Reading

PlGF surfaces in discussions of growth factors, angiogenesis, and endothelial peptides because it sits in the same receptor family as VEGF and because it is one of the more clinically established circulating biomarkers in that family. Anyone reading about angiogenic signalling, neuropilin co-receptors, or placental biology is likely to meet it. It is worth keeping the distinction clear: the published work described above measured PlGF or removed it in models — it did not test PlGF as an administered compound in people.

Limitations of the Current Evidence

• Most human findings are observational associations, including the cognition and white matter imaging reports (PMID 41388837, PMID 41154596).
• Assay platforms and units differ between studies, limiting direct comparison of absolute values.
• Mechanistic causality rests on cell and animal models (PMID 32016802, PMID 39173826), which may not translate directly to human physiology.

References

• Placental growth factor deficiency initiates obesity- and aging-associated metabolic syndrome (Metabolism: Clinical and Experimental, 2024)
• Plasma placental growth factor as a susceptibility biomarker for longitudinal cognitive change (Alzheimer's & Dementia, 2025)
• Maternal placental growth factor mediates the association between PM2.5 and its constituents with adverse pregnancy outcomes (Journal of Hazardous Materials, 2025)
• Association of Plasma Placental Growth Factor with White Matter Hyperintensities in Alzheimer's Disease (Biomolecules, 2025)
• Aspirin for evidence-based preeclampsia prevention trial: effects of aspirin on maternal serum pregnancy-associated plasma protein A and placental growth factor trajectories in pregnancy (American Journal of Obstetrics and Gynecology, 2024)
• Expression of placental growth factor mRNA in preeclampsia (International Journal of Reproductive Biomedicine, 2017)
• Placental growth factor promotes metastases of ovarian cancer through MiR-543-regulated MMP7 (Cellular Physiology and Biochemistry, 2015)
• Placental growth factor and pre-eclampsia (Journal of Human Hypertension, 2017)
• Placental growth factor level is correlated with intrapartum fetal heart rate findings (BMC Pregnancy and Childbirth, 2022)
• Expression of placental growth factor, neuropilin-1, and neuropilin-2 in primary pterygium tissue (Graefe's Archive for Clinical and Experimental Ophthalmology, 2024)
• Placental growth factor level in plasma predicts COVID-19 severity and in-hospital mortality (Journal of Thrombosis and Haemostasis, 2021)
• Effect of Placental Growth Factor on Trophoblast-Endothelial Cell Interactions In Vitro (Reproductive Sciences, 2020)