CDK4/6 inhibitor protects chemerin‐induced human granulosa‐lutein cells from apoptosis by inhibiting the p53/p21<sup>waf</sup> pathway

Liu, Ying; Zhang, Lili; Shan, Yanhong; Chen, Jia; Xü, Ying

doi:10.1002/mrd.23241

Cited by 3 publications

(2 citation statements)

References 41 publications

(47 reference statements)

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“…This effect was not observed in the presence of p21 co-expression, suggesting that palbociclib and p21 competed for the stabilization of cyclin D3-CDK4 complexes. Furthermore, recent studies [44,45] showed a potential "protective" role of palbociclib in granulosa cells in regard to chemerin, which is an adipokine secreted mainly from adipose tissue that causes reactive oxygen species (ROS) accumulation and triggers apoptosis in mouse granulosa cells. Evidence suggests that palbociclib has an antiapoptotic effect on immortalized human granulosa-lutein (hGL) cells treated with chemerin.…”

Section: Role Of Exogenous Cdk Inhibitors (Cdki) In the Ovarymentioning

confidence: 99%

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

Scavone,

Ottonello,

Blondeaux

et al. 2023

Cancers

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The combination of cyclin-dependent kinase (CDK) 4/6 inhibitors with endocrine therapy is the standard treatment for patients with HR+/HER2− advanced breast cancer. Recently, this combination has also entered the early setting as an adjuvant treatment in patients with HR+/HER2− disease at a high risk of disease recurrence following (neo)adjuvant chemotherapy. Despite their current use in clinical practice, limited data on the potential gonadotoxicity of CDK4/6 inhibitors are available. Hence, fully informed treatment decision making by premenopausal patients concerned about the potential development of premature ovarian insufficiency and infertility with the proposed therapy remains difficult. The cell cycle progression of granulosa and cumulus cells is a critical process for ovarian function, especially for ensuring proper follicular growth and acquiring competence. Due to the pharmacological properties of CDK4/6 inhibitors, there could be a potentially negative impact on ovarian function and fertility in women of reproductive age. This review aims to summarize the role of the cyclin D-CDK4 and CDK6 complexes in the ovary and the potential impact of CDK4/6 inhibition on its physiological processes.

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Section: Role Of Exogenous Cdk Inhibitors (Cdki) In the Ovarymentioning

confidence: 99%

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

Scavone,

Ottonello,

Blondeaux

et al. 2023

Cancers

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“…One targeted therapy for CDK inhibition is palbociclib, which may slow the growth of advanced stage breast cancers. In line with this, Palbociclib was used to protect chemin-induced human granulosa cells from apoptosis, acting to inhibit the p53/p21 pathway (Li et al, 2019).…”

Section: Introductionmentioning

confidence: 95%

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition

Ataei-Nazari

Amoushahi

Madsen

et al. 2022

Front. Cell Dev. Biol.

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Introduction: Ovarian follicle development requires tight coordination between several factors to initiate folliculogenesis to generate a mature and fertile egg. Studies have shown that cell cycle factors might contribute to follicle development, hover specific knowledge on individual CDKs and follicle activation has not been investigated. Among cell cycle regulators, CDK6 is a key player through binding to cyclin D resulting DNA synthesis and genome duplication. Interestingly, the CDK6 gene is differentially expressed in oocytes and granulosa cells from human primordial and primary follicles, which suggest a potential role of CDK6 in the primordial-to-primary transition. In this study, we investigated the potential regulatory role of CDK6 in progression of primordial to primary follicle transition using BSJ-03-123 (BSJ), a CDK6-specific degrader.Methods: In mouse ovarian in vitro culture, BSJ reduced the activation of primordial follicles, and reduced follicle development. As a next step, we examined the egg maturation read-out and found that BSJ-treated follicles matured to competent MII eggs with resumption of first meiosis, comparable with the control group.Results: Noteworthy, it appears that inhibition of CDK6 did increase number of apotoptic cells, articular in the granulosa cells, but had no impact on ROS level of cultured ovaries compared to control group, indicating that the cells were not stressed. Oocyte quality thus appeared safe.Discussion: The results of this study indicate that CDK6 plays a role in the primordial-to-primary transition, suggesting that cell cycle regulation is an essential part of ovarian follicle development.

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The role of asprosin in regulating ovarian granulosa- and theca-cell steroidogenesis: a review with comparisons to other adipokines

Maylem,

Schütz,

Spicer

2024

Reprod. Fertil. Dev.

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Adipose tissues produce a variety of biologically active compounds, including cytokines, growth factors and adipokines. Adipokines are important as they function as endocrine hormones that are related to various metabolic and reproductive diseases. The goal of this review was to summarise the role of asprosin, a recently discovered adipokine, and compare its role in ovarian steroidogenesis with that of other adipokines including adiponectin, leptin, resistin, apelin, visfatin, chemerin, irisin, and gremlin 1. The summary of concentrations of these adipokines in humans, rats and other animals will help researchers identify appropriate doses to test in future studies. Review of the literature indicated that asprosin increases androstenedione production in theca cells (Tc), and when cotreated with FSH increases oestradiol production in granulosa cells (Gc). In comparison, other adipokines (1) stimulate Gc oestradiol production but inhibit Tc androgen production (adiponectin), (2) inhibit Gc oestradiol production and Tc androstenedione production (leptin and chemerin), (3) inhibit Gc steroidogenesis with no effect on Tc (resistin), (4) inhibit Gc oestradiol production but stimulate Tc androgen production (gremlin 1), and (5) increase steroid secretion by Gc, with unknown effects on Tc steroidogenesis (apelin and visfatin). Irisin has direct effects on Gc but its precise role (inhibitory or stimulatory) may be species dependent and its effects on Tc will require additional research. Thus, most adipokines have direct effects (either positive or negative) on steroid production in ovarian cells, but how they all work together to create a cumulative effect or disease will require further research.

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CDK4/6 inhibitor protects chemerin‐induced human granulosa‐lutein cells from apoptosis by inhibiting the p53/p21^waf pathway

Cited by 3 publications

References 41 publications

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition

The role of asprosin in regulating ovarian granulosa- and theca-cell steroidogenesis: a review with comparisons to other adipokines

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CDK4/6 inhibitor protects chemerin‐induced human granulosa‐lutein cells from apoptosis by inhibiting the p53/p21waf pathway

Cited by 3 publications

References 41 publications

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

The Role of Cyclin-Dependent Kinases (CDK) 4/6 in the Ovarian Tissue and the Possible Effects of Their Exogenous Inhibition

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition

The role of asprosin in regulating ovarian granulosa- and theca-cell steroidogenesis: a review with comparisons to other adipokines

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Resources

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CDK4/6 inhibitor protects chemerin‐induced human granulosa‐lutein cells from apoptosis by inhibiting the p53/p21^waf pathway