Nicotine downregulates the l-selectin system that mediates cytotrophoblast emigration from cell columns and attachment to the uterine wall

Zdravkovic, Tamara; Genbačev, Olga; Prakobphol, Akraporn; Cvetković, Dragoš; Schanz, A.; McMaster, Michael; Fisher, Susan J.

doi:10.1016/j.reprotox.2006.01.005

Cited by 18 publications

(16 citation statements)

References 30 publications

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“…Dividing cytotrophoblasts in proximal cell columns without virion receptors were not infected except in profoundly affected cases of first trimester primary congenital infection without maternal neutralizing antibodies. In distal cell columns, cytotrophoblasts adhere and roll over each other, facilitating movement from the placental compartment into the uterine wall (62). Here virions bind to integrin ␣1␤1-expressing cells but do not penetrate (Fig.…”

Section: Discussionmentioning

confidence: 99%

Developmental Regulation of Human Cytomegalovirus Receptors in Cytotrophoblasts Correlates with Distinct Replication Sites in the Placenta

Maidji

Genbačev

Chang

et al. 2007

J Virol

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Cytomegalovirus (CMV), the major viral cause of congenital disease, infects the uterus and developing placenta and spreads to the fetus throughout gestation. Virus replicates in invasive cytotrophoblasts in the decidua, and maternal immunoglobulin G (IgG)-CMV virion complexes, which are transcytosed by the neonatal Fc receptor across syncytiotrophoblasts, infect underlying cytotrophoblasts in chorionic villi. Immunity is central to protection of the placenta-fetal unit: infection can occur when IgG has a low neutralizing titer. Here we used immunohistochemical and function-blocking methods to correlate infection in the placenta with expression of potential CMV receptors in situ and in vitro. In placental villi, syncytiotrophoblasts express the virion receptor epidermal growth factor receptor (EGFR) but lack integrin coreceptors, and virion uptake occurs without replication. Focal infection can occur when transcytosed virions reach EGFR-expressing cytotrophoblasts that selectively initiate expression of ␣V integrin. In cell columns, proximal cytotrophoblasts lack receptors and distal cells express integrins ␣1␤1 and ␣V␤3, enabling virion attachment. In the decidua, invasive cytotrophoblasts expressing coreceptors upregulate EGFR, thereby dramatically increasing susceptibility to infection. Our findings indicate that virion interactions with cytotrophoblasts expressing receptors in the placenta (i) change as the cells differentiate and (ii) correlate with spatially distinct sites of CMV replication in maternal and fetal compartments.Human cytomegalovirus (CMV) is the leading cause of congenital viral infection in children, with an incidence in the United States of about 1 to 3% of live births. Primary CMV infection during gestation poses a 40 to 50% risk of intrauterine transmission (5), whereas reactivated infection in seropositive women rarely causes symptomatic disease, highlighting the role of immunity in fetal protection (16). Symptomatic infants have intrauterine growth restriction, and most survivors (28%) have permanent sequelae, including neurological defects, mental retardation, retinopathy, and sensorineuronal deafness (12). Although virus transmission can occur throughout pregnancy, congenital disease is more severe when primary infection takes place during early gestation (54). Intrauterine growth restriction and loss of the fetus without virus transmission, which are associated with congenital CMV infection, originate in placental pathology (3,21).Placentation is a stepwise process whereby specialized cytotrophoblast progenitor cells leave the basement membrane to initiate blood flow, differentiating along two pathways depending on their location (Fig. 1). In floating villi, cells fuse to form a multinucleate syncytial covering attached at one end to the tree-like fetal portion of the placenta. Covered by syncytiotrophoblasts, these villi float in a stream of maternal blood, a source of nutrients and immunoglobulin G (IgG) transported to the fetus. In anchoring villi, cytotrophoblasts switch from an ...

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Section: Discussionmentioning

confidence: 99%

Developmental Regulation of Human Cytomegalovirus Receptors in Cytotrophoblasts Correlates with Distinct Replication Sites in the Placenta

Maidji

Genbačev

Chang

et al. 2007

J Virol

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“…In a subsequent study by the same group, L-selectin, which functions initially in attachment of the embryo to the uterus and later in attaching anchoring villi to the endometrium, was examined in smokers and nonsmokers (Zdravkovic et al, 2006). Immunohistochemical results showed less Lselectin in villi of smokers.…”

Section: Placentamentioning

confidence: 99%

In vitro assessment of reproductive toxicity of tobacco smoke and its constituents

Talbot

2008

Birth Defects Research Pt C

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Epidemiological studies have repeatedly shown that reproductive processes in pregnant women are adversely affected by exposure to cigarette smoke. The potential reproductive targets of smoke during pregnancy include the ovaries, oviducts, uterus, placenta, umbilical cord, and embryo/fetus. In vitro methods for studying the effects of smoke and its individual components have been developed and applied to each of these reproductive targets. In vitro assays have been useful in determining the biological processes that are affected in the reproductive organs and in identifying the cellular and molecular targets of smoke in each organ. In vitro methods have also been used to study the mechanism of action of smoke constituents, such as nicotine, on specific processes in reproductive organs and to screen smoke solutions to identify the molecules that affect reproduction. In general, data collected in vitro have confirmed, extended, and helped explain what has been learned from epidemiological studies. This review summarizes some of the in vitro assays that have been used to study cigarette smoke's effect on the nonpregnant and pregnant female reproductive tract and spotlights examples of their applications.

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“…The actual influences are determined by the individual compounds and the dose to which the endometrium is exposed. Human placental trophoblastic cell lines exposed to compounds within cigarette smoke have been reported to lead to altered expression of epidermal growth factor (387), matrix metalloproteases (121), alterations of hCG secretion (40), L-selectin expression (383), in addition to increased apoptosis, altered cellular architecture, and reduced cytotrophoblast invasion (80,122). Cigarette smoking women are exposed to high levels of cadmium and lead, and these metals have been found within the endometrium of cigarette smokers, correlating with the number of cigarettes smoked and the duration of smoking (289).…”

Section: Implantationmentioning

confidence: 99%

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

Hart

2016

Physiological Reviews

156

109

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Across the Western World there is an increasing trend to postpone childbearing. Consequently, the negative influence of age on oocyte quality may lead to a difficulty in conceiving for many couples. Furthermore, lifestyle factors may exacerbate a couple's difficulty in conceiving due mainly to the metabolic influence of obesity; however, the negative impacts of low peripheral body fat, excessive exercise, the increasing prevalence of sexually transmitted diseases, and smoking all have significant negative effects on fertility. Other factors that impede conception are the perceived increasing prevalence of the polycystic ovary syndrome, which is further exacerbated by obesity, and the presence of uterine fibroids and endometriosis (a progressive pelvic inflammatory disorder) which are more prevalent in older women. A tendency for an earlier sexual debut and to have more sexual partners has led to an increase in sexually transmitted diseases. In addition, there are several genetic influences that may limit the number of oocytes within the ovary; consequently, by postponing attempts at childbearing, a limitation of oocyte number may become evident, whereas in previous generations with earlier conception this potentially reduced reproductive life span did not manifest in infertility. Environmental influences on reproduction are under increasing scrutiny. Although firm evidence is lacking however, dioxin exposure may be linked to endometriosis, phthalate exposure may influence ovarian reserve, and bisphenol A may interfere with oocyte development and maturation. However, chemotherapy or radiotherapy is recognized to lead to ovarian damage and predispose the woman to ovarian failure.

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Nicotine downregulates the l-selectin system that mediates cytotrophoblast emigration from cell columns and attachment to the uterine wall

Cited by 18 publications

References 30 publications

Developmental Regulation of Human Cytomegalovirus Receptors in Cytotrophoblasts Correlates with Distinct Replication Sites in the Placenta

Developmental Regulation of Human Cytomegalovirus Receptors in Cytotrophoblasts Correlates with Distinct Replication Sites in the Placenta

In vitro assessment of reproductive toxicity of tobacco smoke and its constituents

Physiological Aspects of Female Fertility: Role of the Environment, Modern Lifestyle, and Genetics

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