A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β‐2‐Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

Lea, Richard G.; Underwood, Jenny; Flanders, K. C.; Hirte, Hal W.; Banwatt, Daljeet; Finotto, Suzetta; Ohno, Isao; Daya, Salim; Harley, Calvin B.; Michel, Magdy; Mowbray, J. F.; Clark, David A.

doi:10.1111/j.1600-0897.1995.tb00919.x

Cited by 87 publications

(36 citation statements)

References 34 publications

(7 reference statements)

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“…More specifically, we demonstrated that exposure of normal endometrial tissues to TCDD prevents the progesterone-associated increase in TGF-ß 2 . Because TGF-ß 2 is critical to maintaining normal pregnancy and preventing maternal rejection of the fetus [55,56] interfering with the production of this growth factor may have broad implications to reproductive processes other than endometriosis. However, this growth factor plays a central role in progesterone-mediated suppression of MMPs, including the ability of progesterone to prevent experimental endometriosis.…”

Section: Discussionmentioning

confidence: 99%

“…Not surprisingly, progesterone-induced expression of TGF-ß 2 is also critical to maintain an appropriate endometrial environment during pregnancy. For example, a subset of women with recurrent spontaneous abortion were found to be deficient in decidua-associated TGF-ß 2 expression [55]. Interestingly, human studies and studies in nonhuman primates indicate that TCDD exposure increases spontaneous abortion [39,40], a uterine event that may be linked mechanistically to the development of endometriosis [41,46].…”

Section: Tcdd As a Disruptor Of Progesterone Actionmentioning

confidence: 99%

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The Potential Role of Environmental Toxins in the Pathophysiology of Endometriosis

Bruner‐Tran¹,

Rier²,

Eisenberg³

et al. 1999

Gynecol Obstet Invest

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Environmental contaminants that are known to disrupt steroid action can influence the development of reproductive diseases. Our group has focused on whether 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) can disrupt steroid regulation of endometrial matrix metalloproteinase (MMP) expression. The MMPs regulate extracellular matrix turnover in normal tissues, but the inappropriate expression of these enzymes is associated with numerous disease states that involve invasive processes. We have previously shown that secretion of MMPs by human endometrium is critical for establishment of ectopic lesions in a nude mouse model of experimental endometriosis. In this report, we show that TCDD exposure promotes establishment of experimental endometriosis by interfering with the ability of progesterone to suppress endometrial MMP expression.

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Section: Discussionmentioning

confidence: 99%

Section: Tcdd As a Disruptor Of Progesterone Actionmentioning

confidence: 99%

The Potential Role of Environmental Toxins in the Pathophysiology of Endometriosis

Bruner‐Tran¹,

Rier²,

Eisenberg³

et al. 1999

Gynecol Obstet Invest

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“…On the other hand, the role of the other isoforms of TGF␤ is still poorly understood. Because TGF␤2-like molecules are released by CD56ϩ natural killer cells and act as an immunosuppressive factor, implication of TGF␤2 in a local immune reaction preventing rejection of allograft has been suggested (Clark et al, 1994;Lea et al, 1995). This may be the case for TGF␤2 expressed by extravillous cytotrophoblast.…”

Section: Figurementioning

confidence: 99%

Characterization of Human Villous and Extravillous Trophoblasts Isolated from First Trimester Placenta

Tarrade

Kuen

Malassiné

et al. 2001

Laboratory Investigation

232

128

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SUMMARY:Trophoblasts of the human placenta differentiate along two pathways to give either extravillous cytotrophoblasts (EVCT) with invasive properties and that are implicated in the implantation process, or villous cytotrophoblasts (VCT) that by cell fusion form multinucleated syncytiotrophoblasts. We report the first isolation and purification of these two cell types from the same chorionic villi of first trimester human placenta. We also studied their differentiation in vitro. Electron microscopy showed that in contrast to VCT, EVCT had no microvilli but contained large fibrinoid inclusions. EVCT cultures required a matrix to invade, and as previously established, VCT cultured on plastic dishes aggregated and fused to form syncytiotrophoblasts. These differentiation processes were characterized by a particular pattern of gene expression as assessed by real-time PCR and confirmed by immunocytochemical analysis of the corresponding proteins. EVCT cultured in vitro expressed high levels of HLA-G, c-erbB2, human placental lactogen, and very little human chorionic gonadotropin. Interestingly, TGF␤2 was a marker of EVCT in vitro and in situ. These data offer a new tool for cell biologists to study the molecular mechanisms involved in human placental development and its pathology. (Lab Invest 2001, 81:1199 -1211.

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“…On the other hand, progesterone has been shown to promote the development of a Th2 response, via an immunomodulatory protein known as progesteroneinduced blocking factor, which inhibits several Th1-type responses in vitro [47,48]. If there is a lack of suppression at the maternofetal interface, due to reduced levels of TGF-b2, a Th1 shift may be induced [49].…”

Section: T-helper 1 Versus T-helper 2 Responsementioning

confidence: 99%

Recurrent miscarriages: What is the role of cytokines?

Calleja‐Agius

Brincat

2008

Gynecological Endocrinology

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Recurrent miscarriage is defined as three or more consecutive miscarriages before 20 weeks of gestation. This condition is a frequent reproductive problem worldwide, affecting up to 1% of couples. Immune effector cell dysfunction has been implicated in the pathogenesis of early pregnancy loss. This dysfunction may involve defects in cytokines, growth factors and immunosuppressive factors at the maternofetal interface. This is a growing research field, especially the role of cytokines in recurrent miscarriage.

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A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β‐2‐Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

Cited by 87 publications

References 34 publications

The Potential Role of Environmental Toxins in the Pathophysiology of Endometriosis

The Potential Role of Environmental Toxins in the Pathophysiology of Endometriosis

Characterization of Human Villous and Extravillous Trophoblasts Isolated from First Trimester Placenta

Recurrent miscarriages: What is the role of cytokines?

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