Senescence and Telomere Homeostasis Might Be Involved in Placenta Percreta—Preliminary Investigation

Geffen, Keren Tzadikevitch; Gal, Hilah; Vainer, Ifat; Markovitch, Ofer; Amiel, Aliza; Krizhanovsky, Valery; Biron‐Shental, Tal

doi:10.1177/1933719117737852

Cited by 7 publications

(6 citation statements)

References 33 publications

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“…The result that pRb was significantly decreased in late AIP placentas compared to late gestational age-matched controls could contribute to cellular senescence in late AIP. A recent study of Tzadikevitch Geffen et al ( 22 ) corroborate our results in respect of a higher expression of senescence marker p21 in late Placenta percreta (mean gestational age week >34 weeks), but they measured a decrease in p16 and p53 expression. These discrepancies could be due to AIP patient cohorts because it remains a challenge to utilize a standardized tissue collection from different pathological stages of AIP with different villi invasion depth ( accreta , increta , and percreta ).…”

Section: Discussionsupporting

confidence: 90%

“…These discrepancies could be due to AIP patient cohorts because it remains a challenge to utilize a standardized tissue collection from different pathological stages of AIP with different villi invasion depth ( accreta , increta , and percreta ). A further limitation of this study is the low amount of AIP tissue samples available due to these rare clinical cases, however the number is quite similar to other studies ( 22 ).…”

Section: Discussionmentioning

confidence: 60%

“…Senescence is in addition a critical process for the regulation of invasion because deeply invaded EVTs in the placental bed undergo senescence when having escaped from the cell cycle ( 53 , 54 ) to prevent the development of choriocarcinoma. Thus, senescence plays an important regulatory role in normal pregnancy and dysregulation of the senescence pathways will lead to placental diseases, such as PE and AIP ( 22 – 24 ). Cellular senescence can be caused by multiple mechanisms ( 55 – 57 ) and is characterized by prolonged G1 cell cycle arrest.…”

Section: Discussionmentioning

confidence: 99%

“…The process of cellular senescence affects trophoblast differentiation and proliferation. Alteration of senescence-related markers on STB may have a relationship with PE and AIP ( 22 – 24 ). Ray J et al ( 25 ) found that in vitro differentiation from CTB to STB coincided with a decrease in cyclin E1, which is a G1/S phase cell cycle regulator that can inhibit cell cycle progression ( 25 ).…”

Section: Introductionmentioning

confidence: 99%

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CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

Duan

Schimmelmann

et al. 2020

Front. Endocrinol.

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Objectives An adequate development of the placenta includes trophoblast differentiation with the processes of trophoblast migration, invasion, cellular senescence and apoptosis which are all crucial to establishing a successful pregnancy. Altered placental development and function lead to placental diseases such as preeclampsia (PE) which is mainly characterized by insufficient trophoblast invasion and abnormally invasive placenta (AIP) disorders ( Placenta accreta , increta , or percreta) which are characterized by excessive trophoblast invasion. Both of them will cause maternal and fetal morbidity/mortality. However, the etiology of these diseases is still unclear. Our previous study has shown that the matricellular protein nephroblastoma overexpressed (NOV, CCN3) induces G0/G1 cell cycle arrest, drives trophoblast cells into senescence and activates FAK and Akt kinases resulting in reduced cell proliferation and enhanced migration capability of the human trophoblast cell line SGHPL-5. The present study focuses on whether CCN3 can alter cell cycle-regulated pathways associated with trophoblast senescence and invasion activity in pathological versus gestational age-matched control placentas. Methods Cell cycle regulator proteins were investigated by immunoblotting and qPCR. For localization of CCN3, p16, p21, and Cyclin D1 proteins, co-immunohistochemistry was performed. Results In early-onset PE placentas, CCN3 was expressed at a significantly lower level compared to gestational age-matched controls. The decrease of CCN3 level is associated with an increase in p53, Cyclin E1 and pRb protein expression, whereas the level of cleaved Notch-1, p21, Cyclin D1, pFAK, pAKT, and pmTOR protein decreased. In term AIP placentas, the expression of CCN3 was significantly increased compared to matched term controls. This increase was correlated to an increase in p53, p16, p21, Cyclin D1, cleaved Notch-1, pFAK, pAkt, and pmTOR whereas pRb was significantly decreased. However, in late PE and early AIP placentas, no significant differences in CCN3, p16, p21, Cyclin D1, p53, and cleaved Notch-1 expression were found when matched to appropriate controls. Conclusions CCN3 expression levels are correlated to markers of cell cycle arrest oppositely in PE and AIP by activating the FAK/AKT pathway in AIP or down-regulating in PE. This may be one mechanism to explain the different pathological features of placental diseases, PE and AIP.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

Duan

Schimmelmann

et al. 2020

Front. Endocrinol.

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“…In another study, in which scientists opted to study telomere homeostasis and senescence expression in trophoblasts from Placenta Percreta (PP), they found that senescence markers p15 and p21 expression were higher in PP compared to the controls and in accordance with our findings p16 and p53 expressions were lower in PP group 25 .…”

Section: Discussionsupporting

confidence: 87%

Molecular investigation of mechanisms considered to cause preterm premature membrane rupture

Demir

Arslan

Ilgaz

et al. 2022

Cukurova Medical Journal

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Purpose: The aim of this study was to investigate the mRNA expression level of p16, CDK4, CDK6, Cyclin D, RB1, and E2F genes in preterm premature rupture of membrane (PPROM) cases and their roles in etiopathogenesis of PPROM. Materials and Methods: Twenty-one pregnancies with PPROM before 34th gestational weeks (study group) were compared with twenty pregnancies with no complication, who gave birth after 37th gestational-week (control group). Both groups chorioamniotic membranes were compared for mRNA expression of p16, cyclin D, CDK4, CDK6, RB1 and E2F genes. Results: The mRNA expression levels of p16, cyclin D, CDK4, CDK6, RB1and E2F genes decreased in the PPROM group compared to control group at a statistically significant level. Conclusion: Our findings have shown that oxidative stress may not act on the p16 pathway in these cases. In order to understand the molecular mechanism of PPROM, biomarkers of oxidative stress and aging should be evaluated together with other pathways related to aging and oxidative stress in future studies.

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Telomere erosion as a placental clock: From placental pathologies to adverse pregnancy outcomes

Kohlrausch

Keefe

2020

Placenta

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Senescence and Telomere Homeostasis Might Be Involved in Placenta Percreta—Preliminary Investigation

Abstract: Placenta percreta exhibits telomere alterations and changes in expression of several senescence markers. These might be related to altered trophoblast invasion maturation and placental detachment postpartum.

Cited by 7 publications

References 33 publications

CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

CCN3 Signaling Is Differently Regulated in Placental Diseases Preeclampsia and Abnormally Invasive Placenta

Molecular investigation of mechanisms considered to cause preterm premature membrane rupture

Telomere erosion as a placental clock: From placental pathologies to adverse pregnancy outcomes

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