Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage

Parvanov, Dimitar; Ganeva, Rumiana; Vidolova, Nina; Stamenov, Georgi

doi:10.1007/s10815-021-02182-5

Cited by 10 publications

(6 citation statements)

References 31 publications

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“…This observation seems to be in contrast to normal Mendelian frequencies of birth in p16INK4A knockout mice [ 132 ], but slight deviations from Mendelian inheritance might become obvious only when analyzing large numbers of pups [ 115 ] and implantation defects would be only detectable if the female mice in mating are p16INK4A knockout instead of heterozygotes. p16INK4A expression was also described in human endometrium during pregnancy [ 133 ].…”

Section: P16ink4a P14arf/p19arf and P21 In Organ Developmentmentioning

confidence: 99%

The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis

Wagner

2022

Cells

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It is widely accepted that senescent cells accumulate with aging. They are characterized by replicative arrest and the release of a myriad of factors commonly called the senescence-associated secretory phenotype. Despite the replicative cell cycle arrest, these cells are metabolically active and functional. The release of SASP factors is mostly thought to cause tissue dysfunction and to induce senescence in surrounding cells. As major markers for aging and senescence, p16INK4, p14ARF/p19ARF, and p21 are established. Importantly, senescence is also implicated in development, cancer, and tissue homeostasis. While many markers of senescence have been identified, none are able to unambiguously identify all senescent cells. However, increased levels of the cyclin-dependent kinase inhibitors p16INK4A and p21 are often used to identify cells with senescence-associated phenotypes. We review here the knowledge of senescence, p16INK4A, p14ARF/p19ARF, and p21 in embryonic and postnatal development and potential functions in pathophysiology and homeostasis. The establishment of senolytic therapies with the ultimate goal to improve healthy aging requires care and detailed knowledge about the involvement of senescence and senescence-associated proteins in developmental processes and homeostatic mechanism. The review contributes to these topics, summarizes open questions, and provides some directions for future research.

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Section: P16ink4a P14arf/p19arf and P21 In Organ Developmentmentioning

confidence: 99%

The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis

Wagner

2022

Cells

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“…Immunohistochemical analysis showed a significant difference in p16 staining between AMA and YMA luminal epithelia with higher expression in AMA group. Although it was suggested that a higher amount of p16-positive epithelial cells was required for a supportive environment during the window of implantation, it was also previously shown that p16-staining in endometrial epithelial cells correlated positively with women's age 22,23 . The involvement of p16 in the cellular aging mechanism is associated with its role in cell cycle progression.…”

Section: Discussionmentioning

confidence: 99%

Aging affects ciliated cells development in the human endometrial epithelium

Loid

Obukhova

Kask

et al. 2023

Preprint

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The twenties are typically considered the prime reproductive years for women. However, in today’s modern world, many women are choosing to delay family planning, resulting in an increase of females in their forties seeking fertility treatment. Althoughin vitrofertilization (IVF) with donated oocytes and preimplantation genetic testing may help to address the impact of maternal age, the success rate for IVF treatment in this age group is still significantly lower. While endometrial changes, such as abnormal endometrial thickness, inflammatory background, and altered hormone response signaling, are associated with aging, little is known about the molecular features of endometrial aging and their impact on the ability to support embryo implantation. To better understand age-specific changes, we performed endometrial transcriptome profiling of young and advanced age females, undergoing hormonal replacement therapy (HRT) before frozen embryo transfer, followed by immunohistology analysis and single-cell-based deconvolution. Here, we identified 491 differentially expressed genes pointing to the effect of aging on decidualization, cell signaling, inflammation and endometrial receptivity. Our results indicate that p16INK4amay be involved in cellular senescence and the suppression of metabolic and inflammatory processes essential for endometrial preparation for embryo implantation. We have also shown that the proportion of ciliated cells along with ciliary processes is affected by endometrial aging. These findings have important implications for future strategies aimed at improving infertility treatment in women of advanced reproductive age.

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“…Since there are conflicting results in the literature, and the association between p16 Ink4a , endometriosis, and senescence has only relatively recently been identified, this topic needs further investigation [ 48 ]. Recently, the decrease in p16 Ink4a -positive cells was correlated with higher implantation failure and miscarriage among women submitted to in vitro fertilization (IVF) procedures [ 49 ]. This result could be due to naturally occurring reduced telomerase activity (TA) during the secretory phase of the menstrual cycle [ 50 ], since p16 transfection suppressed TA [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Altered p16Ink4a, IL-1β, and Lamin b1 Protein Expression Suggest Cellular Senescence in Deep Endometriotic Lesions

Malvezzi

Dobo

Filippi

et al. 2022

IJMS

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Endometriosis causes immunological and cellular alterations. Endometriosis lesions have lower levels of lamin b1 than the endometrium. Moreover, high levels of pro-inflammatory markers are observed in the peritoneal fluid, follicular fluid, and serum in endometriosis lesions. Thus, we hypothesized that the accumulation of senescent cells in endometriosis tissues would facilitate endometriosis maintenance in an inflammatory microenvironment. To study senescent cell markers and the senescence-associated secretory phenotype (SASP) in endometriosis lesions, we conducted a cross-sectional study with 27 patients undergoing video laparoscopy for endometriosis resection and 19 patients without endometriosis. Endometriosis lesions were collected from patients with endometriosis, while eutopic endometrium was collected from patients both with and without endometriosis. Tissues were evaluated for senescence markers (p16Ink4a, lamin b1, and IL-1β) and interleukin concentrations. The expression of p16Ink4a increased in lesions compared to that in eutopic endometrium from endometriosis patients in the secretory phase. In the proliferative phase, lesions exhibited lower lamin b1 expression but higher IL-4 expression than the eutopic endometrium. Further, IL-1β levels were higher in the lesions than in the eutopic endometrium in both the secretory and proliferative phases. We believe that our findings may provide targets for better therapeutic interventions to alleviate the symptoms of endometriosis.

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Decreased number of p16-positive senescent cells in human endometrium as a marker of miscarriage

Cited by 10 publications

References 31 publications

The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis

The Senescence Markers p16INK4A, p14ARF/p19ARF, and p21 in Organ Development and Homeostasis

Aging affects ciliated cells development in the human endometrial epithelium

Altered p16Ink4a, IL-1β, and Lamin b1 Protein Expression Suggest Cellular Senescence in Deep Endometriotic Lesions

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