Publications by authors named "Jacqueline Guettler"

Article Synopsis
  • Low molecular weight heparins (LMWH) are used in pregnancy to prevent or treat thromboembolic events and may have protective effects against preeclampsia, although their use in this context is debated.
  • Recent research shows that LMWH can reduce pregnancy loss and inflammation-related activation of the NLRP3 inflammasome in trophoblasts, which are crucial for a healthy pregnancy.
  • The mechanism involves LMWH activating the heparin-binding epidermal growth factor (HBEGF) pathway, which prevents inflammasome activation and could provide a rationale for using LMWH in managing preeclampsia.
View Article and Find Full Text PDF

The study of very early human placentation is largely limited due to ethical restrictions on the use of embryonic tissue and the fact that the placental anatomy of common laboratory animal models varies considerably from that of humans. In recent years several promising models, including trophoblast stem cell-derived organoids, have been developed that have also proven useful for the study of important trophoblast differentiation processes. However, the consideration of maternal blood flow in trophoblast invasion models currently appears to be limited to animal models.

View Article and Find Full Text PDF

The existing ex vivo placental explant culture models are primarily grounded in static culture systems using well plates. However, these models inadequately reflect the dynamic in utero setting, where the placenta encounters constant slight shear stress due to plasma or blood flow. To address this limitation, a flow culture system has been devised to bring ex vivo placental explant cultivation closer to the in utero flow conditions experienced within the maternal body.

View Article and Find Full Text PDF

Background: The human placenta, a tissue with a lifespan limited to the period of pregnancy, is exposed to varying shear rates by maternal blood perfusion depending on the stage of development. In this study, we aimed to investigate the effects of fluidic shear stress on the human trophoblast transcriptome and metabolism.

Results: Based on a trophoblast cell line cultured in a fluidic flow system, changes caused by shear stress were analyzed and compared to static conditions.

View Article and Find Full Text PDF

Tissue insults in response to inflammation, hypoxia and ischemia are accompanied by the release of ATP into the extracellular space. There, ATP modulates several pathological processes, including chemotaxis, inflammasome induction and platelet activation. ATP hydrolysis is significantly enhanced in human pregnancy, suggesting that increased conversion of extracellular ATP is an important anti-inflammatory process in preventing exaggerated inflammation, platelet activation and hemostasis in gestation.

View Article and Find Full Text PDF
Article Synopsis
  • The study investigates the localization and expression of sphingosine-1-phosphate receptors (S1PR1-S1PR3) in the human placenta throughout different stages of pregnancy, focusing on the first trimester, pre-term, and term cases.
  • Results indicate that S1PR2 predominates in early pregnancy but decreases as pregnancy progresses, while S1PR1 and S1PR3 increase toward term.
  • The expression of S1PR2 is negatively affected by platelet-derived factors in trophoblast cells, suggesting that changing conditions in the placenta could influence receptor dynamics throughout gestation.
View Article and Find Full Text PDF

Angiotensin II receptor 1 blockers are commonly used to treat hypertension in women of childbearing age. While the fetotoxic effects of these drugs in the second and third trimesters of pregnancy are well documented, their possible impacts on placenta development in early gestation are unknown. Candesartan, a member of this group, also acts as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist, a key regulator shown to be important for placental development.

View Article and Find Full Text PDF

In human pregnancy, maternal platelet counts decrease with each trimester, reaching a reduction by approximately ten percent at term in uncomplicated cases and recover to the levels of the non-pregnant state a few weeks postpartum. The time when maternal platelets start to occur in the early human placenta most likely coincides with the appearance of loosely cohesive endovascular trophoblast plugs showing capillary-sized channels by mid first trimester. At that time, platelets accumulate in intercellular gaps of anchoring parts of trophoblast columns and start to adhere to the surface of placental villi and the chorionic plate.

View Article and Find Full Text PDF

Upon activation, maternal platelets provide a source of proinflammatory mediators in the intervillous space of the placenta. Therefore, platelet-derived factors may interfere with different trophoblast subtypes of the developing human placenta and might cause altered hormone secretion and placental dysfunction later on in pregnancy. Increased platelet activation, and the subsequent occurrence of placental fibrinoid deposition, are linked to placenta pathologies such as preeclampsia.

View Article and Find Full Text PDF

During pregnancy, freely floating placental villi are adapted to fluid shear stress due to placental perfusion with maternal plasma and blood. In vitro culture of placental villous explants is widely performed under static conditions, hoping the conditions may represent the in utero environment. However, static placental villous explant culture dramatically differs from the in vivo situation.

View Article and Find Full Text PDF

In early human gestation, maternal arterial blood flow into the intervillous space of the developing placenta is obstructed by invaded trophoblasts, which form cellular plugs in uterine spiral arteries. These trophoblast plugs have recently been described to be loosely cohesive with clear capillary-sized channels into the intervillous space by 7 weeks of gestation. Here, we analysed localisation of maternal platelets at the maternal-foetal interface of human first trimester pregnancy, and tested the hypothesis whether HLA-G, which is primarily expressed by extravillous trophoblasts, affects aggregation and adhesion of isolated platelets.

View Article and Find Full Text PDF

With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across different trophoblast subtypes. Amongst many other cell types, trophoblasts are able to sense fluid shear stress through mechanotransduction. Failure in the adaption of trophoblasts to fluid shear stress is suggested to contribute to pregnancy disorders.

View Article and Find Full Text PDF

During histiotrophic nutrition of the embryo, maternal platelets may be the first circulating maternal cells that find their way into the placental intervillous space through narrow intertrophoblastic gaps within the plugs of spiral arteries. Activation of platelets at the maternal-fetal interface can influence trophoblast behavior and has been implicated in serious pregnancy pathologies. Here, we show that platelet-derived factors impaired expression and secretion of the human chorionic gonadotropin beta-subunit (βhCG) in human first trimester placental explants and the trophoblast cell line BeWo.

View Article and Find Full Text PDF

Human pregnancy relies on hemochorial placentation, including implantation of the blastocyst and deep invasion of fetal trophoblast cells into maternal uterine blood vessels, enabling direct contact of maternal blood with placental villi. Hemochorial placentation requires fast and reliable hemostasis to guarantee survival of the mother, but also for the neonates. During human pregnancy, maternal platelet count decreases gradually from first, to second, and third trimester.

View Article and Find Full Text PDF