The influence of the maternal uterine immune response on placentation in human subjects

Annals of the New York Academy of Sciences

Parry

2001

The placenta is a dynamic organ whose structure and function change throughout pregnancy. There is compelling evidence that the placenta plays an integral role in the vertical transmission of viruses, such as cytomegalovirus and human immunodeficiency virus, from the mother to the fetus. Although the sequelae of congenital viral infection (i.e., fetal anomalies, intrauterine fetal death, and persistent postnatal infection) may be devastating, very little is known about the passage of viruses across the placenta and the pathologic consequences of placental viral infection. We postulate that the syncytiotrophoblast, which forms a continuous barrier between the maternal and fetal circulation, is relatively resistant to viral infection. In support of this hypothesis, we observed that the susceptibility of trophoblast cells to infection by adenovirus and herpes simplex virus and the expression of viral receptors were reduced as trophoblast cells terminally differentiated into syncytiotrophoblast. Conversely, we observed that undifferentiated, extravillous trophoblast cells, which are susceptible to adenovirus infection, underwent pathologic changes (i.e., apoptosis) when infected by adenovirus in the presence of decidual lymphocytes (which were used to simulate the maternal immune response to viral infection). Based on these findings, we speculate that viral infection of extravillous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction.

Section: Placental Developmentmentioning

confidence: 99%

The Mechanisms of Placental Viral Infection

Annals of the New York Academy of Sciences

Parry

2001

“…These intermediate, or extravillous, trophoblast cells engage in a dialogue with maternal cells and probably mediate suppression of the maternal immune system against the semiallogeneic conceptus [13,14]. The inflammatory response to HSV infection at the maternal-fetal interface has been postulated to abrogate normal placentation and to predispose both the mother and fetus to adverse reproductive outcomes, including miscarriage, fetal growth restriction, and preeclampsia [8,13,15]. In the other pathway of placental development, mononucleated cytotrophoblast cells within the placental villi terminally differentiate into the multinucleated syncytiotrophoblast.…”

Section: Introductionmentioning

confidence: 99%

“…In one pathway, a subset of undifferentiated cytotrophoblast cells in anchoring placental villi invades maternal tissues and blood vessels within the decidua and myometrium. These intermediate, or extravillous, trophoblast cells engage in a dialogue with maternal cells and probably mediate suppression of the maternal immune system against the semiallogeneic conceptus [13,14]. The inflammatory response to HSV infection at the maternal-fetal interface has been postulated to abrogate normal placentation and to predispose both the mother and fetus to adverse reproductive outcomes, including miscarriage, fetal growth restriction, and preeclampsia [8,13,15].…”

Section: Introductionmentioning

confidence: 99%

Syncytiotrophoblast Is a Barrier to Maternal-Fetal Transmission of Herpes Simplex Virus1

Biology of Reproduction

Makrigiannakis

et al. 2002

Herpes simplex virus (HSV)-1 has been discovered in placental tissue from spontaneous miscarriages, but reports of transplacental transmission and fetal infection are extremely rare. Previously, we demonstrated that the villous syncytiotrophoblast, which forms a continuous layer between the maternal and fetal circulation, is resistant to HSV entry. Here, we tested our hypothesis that the villous syncytiotrophoblast prevents transplacental transmission of HSV secondary to decreased expression of HSV entry mediators (HveA, HveB, and HveC). In addition, we investigated the ability of HSV to infect extravillous trophoblast cells, which mediate placental attachment to the uterine wall, and the expression of HSV receptors in these cells. We performed fluorescence-activated cell sorting (FACS) analyses and immunostaining to demonstrate that HveA, HveB, and HveC were not expressed in third-trimester villous trophoblast cells. Consequently, villous explants obtained from third-trimester placentas were resistant to infection by a recombinant HSV-1 vector, HSV-1 KOS, but approximately 20% of mesenchymal cells within the villous core were infected when villous explants were pretreated with trypsin to disrupt the villous trophoblast layer. Conversely, FACS analysis and immunostaining demonstrated that extravillous trophoblast cells expressed HveA, HveB, and HveC, and these cells were efficiently infected by HSV vectors. Infection of extravillous trophoblast cells by HSV-1 was not reduced when the cells were pretreated with an antibody against HveA but was partially reduced when the cells were pretreated with antibodies directed against HveB and HveC. Thus, the decreased expression of herpesvirus entry mediators in villous syncytiotrophoblast prevents placental villous infection, thereby limiting maternal-fetal transmission of HSV.

“…These intermediate, or extravillous, trophoblast cells engage in a dialogue with maternal cells and probably mediate suppression of the maternal immune system against the semiallogeneic conceptus [7,8]. The inflammatory response to infection at the maternal-fetal interface has been postulated to abrogate normal placentation and predispose the mother and fetus to adverse reproductive outcomes, including miscarriage, fetal growth restriction, and preeclampsia [8][9][10]. In the other pathway of placental development, mononucleated cytotrophoblast cells within the placental villi differentiate into the multinucleated syncytiotrophoblast.…”

Section: Introductionmentioning

confidence: 99%

“…In one pathway, a subset of undifferentiated cytotrophoblast cells in anchoring placental villi invades maternal tissues and blood vessels within the decidua and myometrium. These intermediate, or extravillous, trophoblast cells engage in a dialogue with maternal cells and probably mediate suppression of the maternal immune system against the semiallogeneic conceptus [7,8]. The inflammatory response to infection at the maternal-fetal interface has been postulated to abrogate normal placentation and predispose the mother and fetus to adverse reproductive outcomes, including miscarriage, fetal growth restriction, and preeclampsia [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Differential Expression of the Coxsackievirus and Adenovirus Receptor Regulates Adenovirus Infection of the Placenta1

Biology of Reproduction

Makrigiannakis

et al. 2001

The molecular mechanisms and pathologic significance of placental viral infections are poorly understood. We investigated factors that regulate placental infection by adenovirus, which is the most common viral pathogen identified in fetal samples from abnormal pregnancies (i.e., fetal growth restriction, oligohydramnios, and nonimmune fetal hydrops). We also determined the pathologic significance of placental adenovirus infection. Northern hybridization, flow cytometry, and immunostaining revealed that placental expression of the coxsackievirus and adenovirus receptor (CAR) varied with gestational age and trophoblast phenotype. The CAR was continuously expressed in invasive or extravillous trophoblast cells but not in villous trophoblast cells. We postulate that the villous syncytiotrophoblast, which does not express CAR and is resistant to adenovirus infection, limits the transplacental transmission of viral pathogens, including adenovirus. Conversely, extravillous trophoblast cells underwent apoptosis when infected by adenovirus in the presence of decidual lymphocytes (which simulated the maternal immune response to viral infection). Thus, adenovirus infection and/or the maternal immune response to adenovirus infection induced the death of placental cell types that expressed CAR. Consequently, we speculate that adenovirus infection of extra-villous trophoblast cells may negatively impact the process of placental invasion and predispose the mother and fetus to adverse reproductive outcomes that result from placental dysfunction.