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The placenta in the second trimester, a midlife crisis
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Abstracts / Placenta 57 (2017) 225e335
PL1. EARLY PLACENTAL AND EMBRYONIC HEALTH
PL3. CAN WOMEN MAKE BETTER PLACENTAS?
Eric A.P. Steegers. Erasmus MC, Rotterdam, The Netherlands
Michael Nelson. Washington University School of Medicine, St. Louis, USA
The first trimester of pregnancy is highly important with regard to cell multiplication, differentiation and epigenetic programming of embryonic and placental tissues and several pregnancy complications originate during this period. Although the first trimester is perhaps the most important period of prenatal development, so far first trimester embryonic growth has received less attention. New opportunities of three-dimensional ultrasound techniques in combination with the virtual reality (VR) technology of the BARCO I-Space and V-scope visualization software enable depth perception and therefore have tremendously improved the possibilities of visualization of the human embryo. Using this technique in prospectively obtained serial ultrasound scans during the first trimester of pregnancy now reveals associations between maternal age, folic acid supplement use, dietary patterns, smoking and embryonic crown rump length and volume measurements as outcomes of embryonic health. Moreover, being small as an embryo appears to be associated with an increased risk of being born small for gestational age, but also with an enhanced cardiovascular risk profile in childhood. These imaging techniques also enable scoring of embryonic development according to the external morphological criteria of the Carnegie stages. Very recently it was shown that a low level of vitamin B12 and high level of homocysteine, as biomarkers of one carbon metabolism involved in epigenetic programming, significantly delay embryonic development. Next to embryonic growth and morphogenesis, early human placental development is of crucial importance for pregnancy outcome and future health during the lifecourse. The success or failure of early placental development can possibly be established through innovative imaging of the uteroplacental vascularization. Current state-of-the-art three-dimensional (3D) power Doppler ultrasound in combination with our VR system enables utero- and uteroplacental vascular volume measurements from the preconception period onwards throughout early pregnancy. The development of such imaging biomarkers may provide more understanding of the (patho)physiology of early placental development and possibly contribute to the improvement of early prediction and prevention of placenta-related pregnancy complications.
Placental maldevelopment and placental dysfunction go hand in hand. Placental injury contributes to both entities when exogenous insults evolve in placental tissues. Fibrin commonly marks local and systemic areas of injury in vascular spaces, and this also is true for villous trophoblast that lines the intervillous space and the decidua, which interfaces the chorioallantoic placenta at the basal plate. My abstract is dedicated to the late, esteemed Dr. Harold Fox, whose expertise in pathology offered us a chronicle of what happens when placental pathology and placental dysfunction emerges in pregnancy. My presentation in honor of Dr. Fox will focus on therapeutic approaches that may limit the human placenta’s susceptibility to maldevelopment, injury, or both. I will describe studies whereby the phytochemicals in pomegranate juice are able to modulate the injury to human placentas in vivo during labor, in villi in explant culture exposed to chemical insults, and in term human trophoblasts differentiating in vitro in the presence of low or ambient oxygen tensions. I also will describe recent studies that indicate a change in a pregnant woman’s dietary intake of two prominent free fatty acids, palmitic acid and oleic acid, can modulate the biology of human villous trophoblasts, by inducing cell destruction when exposed to palmitate and inducing fat storage when exposed to oleate. Finally, I will discuss potential roles of bioactive vitamin D in the placenta, especially when women are able to achieve a level postulated to yield optimal effects from this pleiotropic hormone. Can women influence placental development and optimize placental function? I am optimistic, yet I am not sure. This stated, our studies offer insights into options for women to modulate placental responses.
http://dx.doi.org/10.1016/j.placenta.2017.07.019
Gil Mor. Yale University School of Medicine, New Haven, USA
PL2. THE PLACENTA IN THE SECOND TRIMESTER, A MIDLIFE CRISIS Brian Cox. University of Toronto, Toronto, Canada The second trimester of the human placenta is likely the least studied, which is maybe why I have been tasked with presenting on this subject (If you recall I was the first one thrown out of the balloon in Paris…). The paucity of data on the 2nd trimester arises from the greater rarity of samples from this time period. However, the 2nd trimester is of great importance as it links the pre-maternal blood perfusion development of the first trimester to the slower growth and vascular maturation of the third trimester placenta. Newer data using Doppler and 3D reconstruction of vascular development has helped to shed light on this stage of placental development. I will present a review of our understanding of this stage focusing on growth rates, villus and vascular formation, and gene expression. I will also link these observations to findings in placental pathologies that indicate the second trimester as a critical developmental window. From this review, I propose that errors in the development of the second lead to stalled or precocious ageing and that each results in a poor placental function that can lead to fetal and maternal pathologies. http://dx.doi.org/10.1016/j.placenta.2017.07.020
http://dx.doi.org/10.1016/j.placenta.2017.07.021
S1.1. THE UNIQUE IMMUNOLOGIC AND MICROBIAL ASPECTS OF PREGNANCY
Pregnancy is a process that engages at least three phases of unique inflammatory profiles, which corresponds to the stage of gestation. The normal milieu is created in part by the normal microbiota and can be disrupted by external stimuli such as viral infections. The success of pregnancy thus depends highly on the ability of the immune system to maintain the status quo of each particular stage. The trophoblast represents the first point of contact between the blastocyst and the maternal decidua. Current studies demonstrate that during implantation and early placentation, the trophoblast has an active role in shaping the immunological milieu at the implantation site by attracting and educating immune cells and shaping the immune cells’ subsequent response to external stimuli. We characterized the response of TLR4 ligation by LPS in both mouse and human trophoblast cells, as well as in trophoblast-educated macrophages, and observed that instead of inducing a classical NF-kB-inflammatory response, it induced the production of type I interferons (IFNs). We showed that IFNb is a critical immune modulator during pregnancy as demonstrated in studies using IFN receptor-deficient mice. Furthermore, we have shown that IFN-induced genes play a central role in the protection of the mother and fetus during a viral infection. http://dx.doi.org/10.1016/j.placenta.2017.07.022
Abstracts / Placenta 57 (2017) 225e335
PL1. EARLY PLACENTAL AND EMBRYONIC HEALTH
PL3. CAN WOMEN MAKE BETTER PLACENTAS?
Eric A.P. Steegers. Erasmus MC, Rotterdam, The Netherlands
Michael Nelson. Washington University School of Medicine, St. Louis, USA
The first trimester of pregnancy is highly important with regard to cell multiplication, differentiation and epigenetic programming of embryonic and placental tissues and several pregnancy complications originate during this period. Although the first trimester is perhaps the most important period of prenatal development, so far first trimester embryonic growth has received less attention. New opportunities of three-dimensional ultrasound techniques in combination with the virtual reality (VR) technology of the BARCO I-Space and V-scope visualization software enable depth perception and therefore have tremendously improved the possibilities of visualization of the human embryo. Using this technique in prospectively obtained serial ultrasound scans during the first trimester of pregnancy now reveals associations between maternal age, folic acid supplement use, dietary patterns, smoking and embryonic crown rump length and volume measurements as outcomes of embryonic health. Moreover, being small as an embryo appears to be associated with an increased risk of being born small for gestational age, but also with an enhanced cardiovascular risk profile in childhood. These imaging techniques also enable scoring of embryonic development according to the external morphological criteria of the Carnegie stages. Very recently it was shown that a low level of vitamin B12 and high level of homocysteine, as biomarkers of one carbon metabolism involved in epigenetic programming, significantly delay embryonic development. Next to embryonic growth and morphogenesis, early human placental development is of crucial importance for pregnancy outcome and future health during the lifecourse. The success or failure of early placental development can possibly be established through innovative imaging of the uteroplacental vascularization. Current state-of-the-art three-dimensional (3D) power Doppler ultrasound in combination with our VR system enables utero- and uteroplacental vascular volume measurements from the preconception period onwards throughout early pregnancy. The development of such imaging biomarkers may provide more understanding of the (patho)physiology of early placental development and possibly contribute to the improvement of early prediction and prevention of placenta-related pregnancy complications.
Placental maldevelopment and placental dysfunction go hand in hand. Placental injury contributes to both entities when exogenous insults evolve in placental tissues. Fibrin commonly marks local and systemic areas of injury in vascular spaces, and this also is true for villous trophoblast that lines the intervillous space and the decidua, which interfaces the chorioallantoic placenta at the basal plate. My abstract is dedicated to the late, esteemed Dr. Harold Fox, whose expertise in pathology offered us a chronicle of what happens when placental pathology and placental dysfunction emerges in pregnancy. My presentation in honor of Dr. Fox will focus on therapeutic approaches that may limit the human placenta’s susceptibility to maldevelopment, injury, or both. I will describe studies whereby the phytochemicals in pomegranate juice are able to modulate the injury to human placentas in vivo during labor, in villi in explant culture exposed to chemical insults, and in term human trophoblasts differentiating in vitro in the presence of low or ambient oxygen tensions. I also will describe recent studies that indicate a change in a pregnant woman’s dietary intake of two prominent free fatty acids, palmitic acid and oleic acid, can modulate the biology of human villous trophoblasts, by inducing cell destruction when exposed to palmitate and inducing fat storage when exposed to oleate. Finally, I will discuss potential roles of bioactive vitamin D in the placenta, especially when women are able to achieve a level postulated to yield optimal effects from this pleiotropic hormone. Can women influence placental development and optimize placental function? I am optimistic, yet I am not sure. This stated, our studies offer insights into options for women to modulate placental responses.
http://dx.doi.org/10.1016/j.placenta.2017.07.019
Gil Mor. Yale University School of Medicine, New Haven, USA
PL2. THE PLACENTA IN THE SECOND TRIMESTER, A MIDLIFE CRISIS Brian Cox. University of Toronto, Toronto, Canada The second trimester of the human placenta is likely the least studied, which is maybe why I have been tasked with presenting on this subject (If you recall I was the first one thrown out of the balloon in Paris…). The paucity of data on the 2nd trimester arises from the greater rarity of samples from this time period. However, the 2nd trimester is of great importance as it links the pre-maternal blood perfusion development of the first trimester to the slower growth and vascular maturation of the third trimester placenta. Newer data using Doppler and 3D reconstruction of vascular development has helped to shed light on this stage of placental development. I will present a review of our understanding of this stage focusing on growth rates, villus and vascular formation, and gene expression. I will also link these observations to findings in placental pathologies that indicate the second trimester as a critical developmental window. From this review, I propose that errors in the development of the second lead to stalled or precocious ageing and that each results in a poor placental function that can lead to fetal and maternal pathologies. http://dx.doi.org/10.1016/j.placenta.2017.07.020
http://dx.doi.org/10.1016/j.placenta.2017.07.021
S1.1. THE UNIQUE IMMUNOLOGIC AND MICROBIAL ASPECTS OF PREGNANCY
Pregnancy is a process that engages at least three phases of unique inflammatory profiles, which corresponds to the stage of gestation. The normal milieu is created in part by the normal microbiota and can be disrupted by external stimuli such as viral infections. The success of pregnancy thus depends highly on the ability of the immune system to maintain the status quo of each particular stage. The trophoblast represents the first point of contact between the blastocyst and the maternal decidua. Current studies demonstrate that during implantation and early placentation, the trophoblast has an active role in shaping the immunological milieu at the implantation site by attracting and educating immune cells and shaping the immune cells’ subsequent response to external stimuli. We characterized the response of TLR4 ligation by LPS in both mouse and human trophoblast cells, as well as in trophoblast-educated macrophages, and observed that instead of inducing a classical NF-kB-inflammatory response, it induced the production of type I interferons (IFNs). We showed that IFNb is a critical immune modulator during pregnancy as demonstrated in studies using IFN receptor-deficient mice. Furthermore, we have shown that IFN-induced genes play a central role in the protection of the mother and fetus during a viral infection. http://dx.doi.org/10.1016/j.placenta.2017.07.022