Platelet-derived factors impair placental chorionic gonadotropin beta-subunit synthesis

Journal of Molecular Medicine, 2020 · DOI: https://doi.org/10.1007/s00109-019-01866-x · Published: December 20, 2019

Simple Explanation

Maternal platelets can enter the placental intervillous space early in the first trimester, potentially influencing trophoblast behavior. Platelet-derived factors can impair the synthesis of βhCG, a crucial hormone for maintaining pregnancy. Platelet-derived factors activate Smad3 in trophoblasts, which may interfere with CREB signaling, a pathway important for hCG production. The study suggests an interaction between Smad3 and CREB signaling pathways. The research suggests that sequestration of transcription co-activators CBP/p300 by activated Smad3 may limit placental hCG production. These co-activators are essential for both Smad- and CREB-driven gene expression.

Study Duration

Not specified

Participants

31 human first trimester placenta tissues, BeWo cells

Evidence Level

Not specified

Key Findings

1
Maternal platelets can be detected on the surface of placental villi and in intercellular gaps of trophoblast cell columns from gestational week 5 onwards.
2
Platelet-derived factors activate Smad3 in trophoblasts, indicating a potential link between platelet activation and TGF-β signaling in the placenta.
3
Sequestration of CBP/p300 by activated Smad3 may limit placental hCG production, suggesting a mechanism for how platelet-derived factors impair hCG synthesis.

Research Summary

This study investigates the role of platelet-derived factors on placental βhCG synthesis. It demonstrates that maternal platelets can be detected at the early maternal-fetal interface and that platelet-derived factors impair βhCG synthesis in human first trimester placenta. The research shows that platelet-derived factors activate Smad3 in trophoblasts, and this activation may interfere with forskolin-induced CREB signaling. The findings suggest an interaction between Smad3 and CREB signaling pathways in regulating βhCG synthesis. The study concludes that degranulation of maternal platelets at the early maternal-fetal interface can impair placental βhCG production, without substantially affecting morphological and biochemical differentiation of villous trophoblasts.

Practical Implications

Pregnancy Complications

Impaired placental hCG secretion in response to platelet-derived factors may have serious consequences on pregnancy outcome, given the hormone's role in trophoblast proliferation, differentiation, and invasion.

Preeclampsia Risk

Low hCG concentrations in late first trimester may be associated with increased risk to develop preeclampsia later in pregnancy. This suggests a potential link between early platelet activation and later pregnancy complications.

Therapeutic Interventions

Further research is needed to determine whether antiplatelet therapy in early gestation can abolish impaired hCG production by blocking platelet activation at the maternal-fetal interface.

Study Limitations

1
The sample size of cell culture experiments in this study is too small to identify minor but statistically significant differences between treatments.
2
It is not possible to assess whether platelets get activated by their passage through fragmentary trophoblast plugs of uterine blood vessels.
3
Co-immunoprecipitation of Smad3 and CBP/p300 failed, possibly due to low endogenous protein levels.

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