Dynamic expression of matrix metalloproteinases (MMP-2, -9 and -14) and the tissue inhibitors of MMPs (TIMP-1, -2 and -3) at the implantation site during tubal pregnancy

Bai, Suxia; Wang, Yan Ling; Qin, Li; Xiao, Zhijie; Piao, Yun

doi:10.1530/rep.1.00283

Cited by 79 publications

(65 citation statements)

References 40 publications

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“…Thus, the reported decrease in the invasive potential of JAR cells after their treatment with preeclamptic serum (Mahameed et al 2005) might be due to high levels of TIMPs present in preeclamptic serum. Overexpression of TIMP1 and TIMP2 is known to reduce tumor growth (Bai et al 2005), and keeping in view the homology between normal placentation and tumor growth, it can be commented that their increased expression might also be contributing to the specific phenotype of preeclampsia involving intrauterine growth retardation and lighter placentas. Significantly higher expressions of MMPs and TIMPs except TIMP1, in placental villi with reference to their respective maternal blood, support the role and importance of these genes in placental invasiveness.…”

Section: Discussionmentioning

confidence: 99%

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Rahat¹,

Sharma²,

Bagga³

et al. 2016

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The invasion cascade exhibited by placental trophoblasts and cancerous cells bears many similarities, and it is attributed to extracellular matrix degradation mediated by matrix metalloproteinases (MMPs). Although proper and controlled invasion by trophoblasts into the maternal uterus is an essential requirement for maintenance of normal pregnancy, any abnormality in this phenomenon results in the development of invasion-related disorders such as gestational trophoblastic diseases (GTDs) and preeclampsia. We studied the epigenetic basis of differential expression of two placental MMPs (MMP2 and MMP9) and tissue inhibitors of metalloproteinases (TIMP2 and TIMP1) during normal gestation and invasion-related disorders, i.e., preeclampsia and GTDs. Our study suggests the association of H3K9/27me3 with differential expression of these MMPs and their inhibitors, which regulate the placental invasion during normal pregnancy, whereas no role of CpG methylation was observed in the differential expression of MMPs/TIMPs. Further, development of GTDs was associated with abnormally higher expression of these MMPs and lower levels of their inhibitors, whereas the reverse trends were observed for MMPs and their TIMPs in case of preeclampsia, in association with abnormal changes in H3K9/27me3. These results suggest the involvement of higher levels of MMPs in an aggressive invasive behavior depicted by GTDs, whereas lower levels of these MMPs in shallow and poor invasive phenotype associated with preeclampsia. Thus, our study shows the significance of a proper balance regulated by histone trimethylation between differential expression of MMPs and their TIMPs for maintaining normal pregnancy and its deregulation as a contributing factor for pathogenesis of invasive disorders during pregnancy.

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Section: Discussionmentioning

confidence: 99%

Imbalance between matrix metalloproteinases and their tissue inhibitors in preeclampsia and gestational trophoblastic diseases

Rahat¹,

Sharma²,

Bagga³

et al. 2016

Reproduction

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“…Recently, it has been proposed that the vascular endothelial growth factor may be the angiogenic factor responsible for the implantation and placentation of an ectopic pregnancy in the human oviduct (Lam et al 2004). The expression of various factors such as matrix metalloproteinases and tissue inhibitor of matrix metalloproteinases may have roles in regulating the controlled invasion of trophoblasts during implantation and placentation during tubal pregnancy (Bai et al 2005).…”

Section: Tubal Pregnanciesmentioning

confidence: 99%

Ectopic pregnancy in animals and humans

Corpa¹

2006

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Ectopic pregnancy denotes a pregnancy occurring elsewhere than in the cavity of the uterus. This pathology has been recognised for years and it causes numerous maternal deaths during the first trimester of pregnancy. While this condition is wellknown in humans, it is rarely diagnosed in animals. However, the causes and mechanisms leading to an ectopic implantation of the ovum are not always clearly defined in humans or animals. Two types of ectopic pregnancy are mainly recognized: (1) tubal pregnancy occurs when an oocyte is fertilized and then remains in the oviduct and (2) abdominal pregnancy occurs when the gestation develops in the peritoneal cavity. The latter may be subdivided into two subtypes: the primary form, when a fertilized oocyte enters the peritoneal cavity and becomes attached to the mesentery or abdominal viscera, and the secondary form, which follows the rupture of an oviduct or the uterus after the fetus has been implanted, and the fetus is expelled into the peritoneal cavity. Cornual, ovarian and cervical ectopic locations are less frequent. Several differences exist in ectopic pregnancies between human beings and animal species. While abdominal pregnancy has been described in both human and animal species, tubal ectopic pregnancies would appear to be restricted to primates. Other than anecdotal cases, this pathological condition does not occur in laboratory, domestic or farm animals. Several factors are described as being the cause of these differences.

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“…The switch to the integrin subunits v and 5 takes place already in the second layer of trophoblast cells, as soon as the latter detach from the basement membrane (Kemp et al, 2002). In tubal pregnancies, MMP-9 and TIMP-1, -2 and -3 are produced by all types of extravillous cytotrophoblast (EVCT) cells, while MMP-2 and -14 mainly exist in distal column cytotrophoblast (CCT) cells and invasive EVCT cells (Bai et al, 2005). In parallel, MMP-14 and TIMP-1 and -2 are increased along the invasive pathway toward maternal interstitium.…”

Section: Wwwintechopencommentioning

confidence: 99%

“…In parallel, MMP-14 and TIMP-1 and -2 are increased along the invasive pathway toward maternal interstitium. MMP-2, -9 and -14 and TIMP-1, -2 and -3 were all detected in the villous CT (VCT) cells (Bai et al, 2005). Another promising technique for early detection of an ectopic pregnancy is that trophoblast cells can be reliably obtained and identified among cervical cells in the first trimester and labeled with antibody to HLA-G.…”

Section: Wwwintechopencommentioning

confidence: 99%