Role of the placenta in fetal programming: underlying mechanisms and potential interventional approaches
Abstract
Adverse influences during fetal life alter the structure and function of distinct cells, organ systems or homoeostatic pathways, thereby ‘programming’ the individual for an increased risk of developing cardiovascular disease and diabetes in adult life. Fetal programming can be caused by a number of different perturbations in the maternal compartment, such as altered maternal nutrition and reduced utero–placental blood flow; however, the underlying mechanisms remain to be fully established. Perturbations in the maternal environment must be transmitted across the placenta in order to affect the fetus. Here, we review recent insights into how the placenta responds to changes in the maternal environment and discuss possible mechanisms by which the placenta mediates fetal programming. In IUGR (intrauterine growth restriction) pregnancies, the increased placental vascular resistance subjects the fetal heart to increased work load, representing a possible direct link between altered placental structure and fetal programming of cardiovascular disease. A decreased activity of placental 11β-HSD-2 (type 2 isoform of 11β-hydroxysteroid dehydrogenase) activity can increase fetal exposure to maternal cortisol, which programmes the fetus for later hypertension and metabolic disease. The placenta appears to function as a nutrient sensor regulating nutrient transport according to the ability of the maternal supply line to deliver nutrients. By directly regulating fetal nutrient supply and fetal growth, the placenta plays a central role in fetal programming. Furthermore, perturbations in the maternal compartment may affect the methylation status of placental genes and increase placental oxidative/nitrative stress, resulting in changes in placental function. Intervention strategies targeting the placenta in order to prevent or alleviate altered fetal growth and/or fetal programming include altering placental growth and nutrient transport by maternally administered IGFs (insulin-like growth factors) and altering maternal levels of methyl donors.
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GDM is associated with increased System A and L activity.
“GDM is associated with increased System A and L activity [150].”
From The Pathophysiology of Gestational Diabetes Mellitus (2018) · cites this paper as [150]
The placenta is a central integrative organ because it senses and responds to maternal nutrients, hormones, inflammatory mediators and environmental agents through vascular, transport, endocrine and molecular functions.
“The placenta is a central integrative organ because it senses and responds to maternal nutrients, hormones, inflammatory mediators and environmental agents through vascular, transport, endocrine and molecular functions [140,141,142].”
From Placental Pathophysiology and Developmental Programming of Adult Cardiometabolic Risk: A Narrative Review of Pregnancy Exposures (2026) · cites this paper as [142]
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- Authors
- Jansson, T., & Powell, T. L.
- Affiliations
- University of Cincinnati (US)
- Venue
- Clinical Science
- Publisher
- Portland Press Ltd.
- Published
- 2007-06-01
- Volume
- 113
- Issue
- 1
- Pages
- 1-13
- ISSN
- 0143-5221 (ISSN-L)
- 1470-8736
- OpenAlex
- W1994919529
- Cited by
- 542
- References
- 9
- Citations by year
- 2026: 23 · 2025: 20 · 2024: 27 · 2023: 30 · 2022: 23 · 2021: 36 · 2020: 34 · 2019: 21 · 2018: 40 · 2017: 31 · 2016: 24 · 2015: 30 · 2014: 29 · 2013: 38 · 2012: 38
- FWCI
- 3.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Keywords
- placenta, fetal programming, fetal growth restriction, placental vascular resistance, 11β-hydroxysteroid dehydrogenase type 2, maternal cortisol, hypertension, placental nutrient transport, oxidative stress, insulin-like growth factor, maternal nutrition, uteroplacental blood flow, placental development
- MeSH terms
- Biological Transport, Female, Humans, Maternal-Fetal Exchange, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Oxidative Stress, Prenatal Nutritional Physiological Phenomena, 11-beta-Hydroxysteroid Dehydrogenases, Fetal Development
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