Pregnancy And Egf: Is It Safe?

Epidermal growth factor (EGF) is a protein that plays a critical role in maintaining healthy skin functions, including the production of collagen, elastin, and hyaluronic acid, which help keep skin thick, dense, smooth, and firm. During pregnancy, EGF is expressed robustly in the placenta, and critical processes such as placental growth and trophoblast fusion depend on its function. While EGF is generally safe, its role in preeclampsia, a hypertensive disorder that can lead to maternal and fetal health risks, is still being explored.

EGF receptor (EGFR) signaling has been linked to preeclampsia, but the underlying mechanisms are not yet fully understood. Altered EGFR expression and activity may contribute to impaired placental function and endothelial dysfunction, which are characteristics of preeclampsia. However, the available data on EGFR ligand expression in preeclampsia is limited and contradictory, making it challenging to determine its precise role in the disease.

Overall, while EGF is essential for healthy skin and plays a role in pregnancy, further research is needed to fully understand its involvement in preeclampsia and other pregnancy-related conditions.

The role of EGF in preeclampsia

Epidermal growth factor (EGF) is a protein that plays a critical role in the development of the placenta and embryo during pregnancy. However, its role in preeclampsia, a hypertensive disease that is a leading cause of maternal morbidity and mortality, is not well understood.

EGF is highly expressed in the placenta and is crucial for placental growth and trophoblast fusion. During pregnancy, trophoblasts synthesise large amounts of EGF protein, which is released into the maternal circulation through syncytiotrophoblast-derived exosomes and microparticles.

While the exact role of EGF in preeclampsia remains to be fully elucidated, some studies suggest that abnormal EGF signalling may contribute to the development and maintenance of the disease. For instance, transcriptome meta-analyses have indicated that altered gene expression of EGF and its ligands may be implicated in impaired placental function associated with preeclampsia. Additionally, there is evidence that EGF signalling can have deleterious effects on pregnancy-adapted vasodilation, which is critical for maintaining healthy blood flow to the mother and developing fetus.

Furthermore, EGF signalling has been shown to be critical for endometrial function during early pregnancy. Ablation of the EGF receptor (EGFR) in mice resulted in severe subfertility, with a significant reduction in litter size. In contrast, ablation of other EGF receptors, such as ERBB2 and ERBB3, had only a modest impact on fertility. These findings suggest that EGF signalling, particularly through EGFR, plays a vital role in the early stages of pregnancy and placental development.

EGF and the placenta

Epidermal growth factor (EGF) is vital for the development of the human placenta. EGF plays a major role in placental implantation, growth, and differentiation. EGF acts on its placental target cells, the trophoblasts, via a specific receptor that belongs to the tyrosine kinase receptor family.

EGF and its receptor are localized in the cytotrophoblast (C-cell) in 4-5 week placentas, and in the syncytiotrophoblast (S-cell) in 6-12 week placentas. EGF stimulates the secretion of human chorionic gonadotrophin (hCG) and human placental lactogen (hPL) without affecting the proliferation of C-cell in 6-12 week placentas.

EGF is expressed robustly in the placenta, and critical processes of pregnancy such as placental growth and trophoblast fusion are dependent on EGF receptor function. Trophoblasts are known to synthesize large amounts of EGF receptor protein, and the placenta regularly releases syncytiotrophoblast-derived exosomes and microparticles into the maternal circulation.

EGF and the risk of hypertensive disease during pregnancy

EGF is a signalling protein that is naturally found in the skin and plays a critical role in maintaining healthy skin functions, including the production of collagen, elastin, and hyaluronic acid. EGF helps keep the skin thick, dense, smooth, and firm. However, the natural production of EGF decreases with age, which can lead to slower cell turnover and repair, resulting in skin sagging and the appearance of fine lines and wrinkles.

Preeclampsia is a hypertensive disorder that occurs during pregnancy and affects 5-10% of all births in the US each year. It is characterised by new-onset hypertension, typically with a blood pressure above 140/90 mmHg, and can affect multiple organ systems in the body, leading to decreased renal function, liver dysfunction, and stroke in more severe forms such as eclampsia.

While the exact role of EGF in the development of preeclampsia is not fully understood, studies have shown that EGF signalling may play a role in the etiology and/or maintenance of the disease. Altered EGF receptor (EGFR) signalling has been implicated in the impaired placental function associated with preeclampsia, and there is evidence that endothelial dysfunction observed in preeclampsia may be related to elevated endothelial EGFR expression.

During pregnancy, trophoblasts synthesise large amounts of EGFR protein, and the placenta releases syncytiotrophoblast-derived exosomes and microparticles into the maternal circulation. These vesicles can fuse with the endothelium, potentially contributing to the symptoms of preeclampsia by interrupting angiogenesis and blocking pregnancy-adapted vasodilatory function.

Overall, while the exact mechanisms are still being elucidated, the available evidence suggests that EGF signalling may play a role in the development and progression of preeclampsia, a hypertensive disorder that can have serious consequences for both mother and fetus.

EGF and the risk of adverse pregnancy outcomes

The epidermal growth factor receptor (EGFR) is a protein expressed in a wide variety of cell types, including the placenta. It is critical for the maintenance of healthy skin functions, such as the production of collagen, elastin, and hyaluronic acid, which help keep skin thick, dense, smooth, and firm. During pregnancy, EGFR plays a crucial role in placental growth, trophoblast fusion, and trophoblast proliferation. However, abnormal EGFR signaling has been linked to preeclampsia, a hypertensive disorder that can lead to maternal and fetal health risks.

While the exact mechanisms are still being explored, studies suggest that abnormal EGFR signaling may disrupt angiogenesis and block pregnancy-adapted vasodilatory function, contributing to the symptoms of preeclampsia. This disruption in vascular function may be due to the transfer of EGFR-rich exosomes and microparticles from the placenta to the maternal vasculature, altering endothelial cell function.

Furthermore, the level of EGFR expression and activity during pregnancy appears to be critical. Both insufficient and excessive EGFR activity have been associated with adverse outcomes, indicating a "Goldilocks zone" where moderate EGFR signaling is essential for healthy placental development and pregnancy outcomes.

In summary, while EGFR plays a vital role in pregnancy, abnormal EGFR signaling and expression levels may increase the risk of adverse pregnancy outcomes, particularly preeclampsia. Further research is needed to fully understand the complex role of EGFR in pregnancy and its potential impact on maternal and fetal health.

EGF and the risk of preterm birth, low birth weight, and preeclampsia

The risk of adverse pregnancy outcomes, including preterm birth, low birth weight, and preeclampsia, is influenced by various factors, and one factor that has been studied is the level of midterm eGFR (estimated glomerular filtration rate). eGFR is a measure of kidney function and can provide insights into the hemodynamic adaptations that occur during pregnancy. In a large observational study, researchers analysed data from 1931 pregnancies and found a unique U-shaped relationship between midterm eGFR and adverse pregnancy outcomes.

The study defined an adverse pregnancy event as a combination of preterm birth (gestational age <37 weeks), low birth weight (<2.5 kg), and preeclampsia. The results showed that the optimal range of midterm eGFR levels was 120–150 ml/min per 1.73 m2, and women with a midterm eGFR below 120 ml/min per 1.73 m2 experienced more complications during pregnancy. Specifically, the risk of preterm birth and low birth weight was higher in women with midterm eGFR levels below the reference range. Additionally, a significant risk for preeclampsia was identified for women with a midterm eGFR of 90–120 or 60–90 ml/min per 1.73 m2.

Another study focused on the epidermal growth factor (EGF) signaling system, which regulates trophoblast differentiation, and its potential role in preeclampsia. Preeclampsia is associated with trophoblast apoptosis and inadequate invasion and remodelling of the uterine spiral arteries. The study found that three members of the EGF family (HBEGF, TGFA, and EGF) were downregulated in placentas with preeclampsia, while p110/EGFR, a potential EGF receptor antagonist, was overexpressed. These findings suggest that disruption of the EGF signaling system may contribute to the abnormal trophoblast development associated with preeclampsia.

In summary, while the studies suggest that EGF levels and kidney function, as measured by eGFR, may play a role in the risk of preterm birth, low birth weight, and preeclampsia, further research is needed to fully understand the underlying mechanisms and establish any causal relationships.

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