Endometrial secretions: creating a stimulatory microenvironment within the human early placenta and implications for the aetiopathogenesis of preeclampsia
Abstract
Endometrial glands represent an important source of nutrients for the conceptus during the first trimester. Their secretions are enriched with carbohydrates, and glycogen accumulates within the syncytiotrophoblast of the placenta. It has been assumed that fetal and placental metabolism follow adult pathways, although it is now appreciated that early development occurs in a low-oxygen environment. In past decades, a novel family of putative insulin mediators, inositol phosphoglycans (IPGs), was discovered. These molecules act as allosteric activators and/or inhibitors of enzymes and transduction proteins involved in the control of cell signalling and metabolic pathways, and determine the specificity of responses after activation of the insulin receptor. One member, IPG P-type, activates pyruvate dehydrogenase phosphatase (PDH-Pase), glycogen synthase phosphatase, and glycerol-3-phosphate acyltransferase. Activation of key phosphatases play a major role in the regulation of glucose disposal by oxidative metabolism via PDH, and the non-oxidative storage by glycogen synthesis, both pathways classically known to be regulated by insulin. High concentrations of IPG P-type in amniotic fluid suggest a role in the regulation of carbohydrate metabolism in the fetal-placental unit. Glycogen accumulation in the syncytiotrophoblast also occurs in preeclamptic pregnancies, and is consistently associated with higher placental levels of IPG P-type. Here, we explore the relationship between nutrients provided by the endometrial glands during early pregnancy, IPG P-type and fetal metabolic requirements. We also discuss whether a disconnect between the placental/fetal metabolic state and oxygen tension could lead to a preeclamptic-type syndrome via leakage of Warburg/IPG mediators into the maternal circulation.
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During the first trimester the conceptus is supported by histotrophic secretions from the endometrial glands, the 'uterine milk'.
“However, it is now accepted that during the first trimester the conceptus is supported by histotrophic secretions from the endometrial glands, the 'uterine milk' (80,83).”
From Placental Origins of Chronic Disease (2016) · cites this paper as [80]
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- Authors
- Burton, G. J., Scioscia, M., & Rademacher, T. W.
- Affiliations
- University of Cambridge (GB)
- Ospedale Sacro Cuore Don Calabria (IT)
- University of Oxford (GB)
- Corresponding author
- Rademacher, T.W.
- Venue
- Journal of Reproductive Immunology
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 89
- Issue
- 2
- Pages
- 118-125
- ISSN
- 0165-0378 (ISSN-L)
- OpenAlex
- W2114818718
- Cited by
- 64
- References
- 82
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 6 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 0.87
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Reproductive Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- endometrial secretion, preeclampsia, inositol phosphoglycans, glucose metabolism, insulin signaling, pyruvate dehydrogenase phosphatase, glycogen synthase, Warburg effect, hypoxia, amniotic fluid, maternal-fetal nutrient transfer
- MeSH terms
- Adult, Endometrium, Exocrine Glands, Female, Humans, Placenta, Pre-Eclampsia, Pregnancy
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