Granulosa Cell Apoptosis in the Ovarian Follicle—A Changing View

Regan, Sheena L.P.; Knight, P. G.; Yovich, John L.; Leung, Yee; Arfuso, Frank; Dharmarajan, Arun

doi:10.3389/fendo.2018.00061

Cited by 142 publications

(104 citation statements)

References 97 publications

(141 reference statements)

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“…The apoptosis rate was also lower in women over 40 years with diminished ovarian reserve compared to a group of the same age with normal ovarian reserve (Regan et al, ). On possible interpretation of these conflicting observations is that cumulus cell apoptosis would increase with advanced age (Lee et al, ) whilst mural CGs apoptosis paradoxically decreases due to a slower turnover of this cell population (Regan et al, ). Furthermore, previous studies may have evaluated mixed cell populations in the follicular fluid aspirate rather than ultra‐pure GCs (Ferrero et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Extrinsic factors such as DNA damage and oxidative stress can activate p53‐specific signaling pathways and trigger the apoptotic cascade (Regan et al, ). Some diseases like endometriosis can lead to an increase in reactive oxygen species (ROS), which results in a lower number of oocytes retrieved and diminished implantation rate during IVF procedures.…”

Section: Introductionmentioning

confidence: 99%

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Clinical correlation of apoptosis in human granulosa cells—A review

Almeida

Ferreira

Silveira

et al. 2018

Cell Biology International

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The quality of oocytes depends on interactions with surrounding granulosa cells. Granulosa cells are essential in normal follicular maturation process since they produce steroidal hormones and growth factors, and they play a crucial role in follicular atresia. The success in reproductive biology and medicine depends on reliable assessment of oocyte and embryo viability which presently mainly bases on oocyte and embryo morphology. Recent investigations have tried to establish an evaluation system for oocyte quality and to predict outcome of in vitro fertilization (IVF) based on the incidence of granulosa cells and cumulus cells apoptosis. Apoptosis of granulosa cells seems to have a negative effect on conception and pregnancy rates in IFV programs. Thus, in this review we present a brief outline of clinical correlation of apoptosis in human granulosa cells and cumulus cells, and its influence upon oocyte quality and IFV outcome. Taken together, understanding the influence of granulosa cell apoptosis on oocyte quality and maturity as well as on embryo health may ultimately allow scientists and clinicians to harness better protocols of ovarian stimulation for infertility treatments.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical correlation of apoptosis in human granulosa cells—A review

Almeida

Ferreira

Silveira

et al. 2018

Cell Biology International

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“…One of the major differences between oocyte loss during ovarian reserve development compared with later oocyte maturation and ovulation is the source of the cell death trigger; in early oogenesis and primordial follicle development, it appears to be the oocyte which, itself, autonomously triggers cell death and loss of the follicle (Morita & Tilly, 1999; Yadav et al, 2018). In contrast, later stage follicle loss results largely from granulosa cells' signals that induce both granulosa cell death as well as oocyte demise (Regan et al, 2018; J. Zhang et al, 2018). Interestingly, work from Blondin and Sirard (1995) suggests that in the cow, low levels of granulosa cell death in pre‐ovulatory follicles result in an oocyte of greater developmental competence compared with oocytes from follicles with no evidence of atresia.…”

Section: Developmental Oocyte Attrition Contrasts With Follicular Atrmentioning

confidence: 99%

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

Grive

2020

Molecular Reproduction Devel

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The mammalian ovarian reserve is comprised of a finite pool of primordial follicles, representing the lifetime reproductive capacity of females. In most mammals, the reserve is produced during embryonic and early postnatal development with oocyte numbers peaking during mid‐to‐late gestation, and then experiencing a dramatic decline continuing until shortly after birth. Oocytes remaining after the bulk of this attrition are subsequently surrounded by a layer of somatic pre‐granulosa cells with these units then referred to as “primordial follicles.” The complex and varied cell death mechanisms intrinsic to this process are not only characteristic of, but also essential for, the proper formation of this pool of follicles, and as a result must be immaculately balanced to ensure long‐term fertility and reproductive health. Too few follicles can lead to Primary Ovarian Insufficiency, resulting in fertility loss and other features of aging, such as an overall shorter lifespan. On the other hand, whereas an excess of follicles might extend reproductive lifespan, this might also be the underlying etiology of other ovarian pathologies. The last decade, in particular, has vastly expanded our understanding of oocyte attrition and determinants of ovarian reserve abundance. By continuing to decipher the intricacies underlying the cell death processes and development of the initial primordial follicle pool, we may be in a much better position to understand idiopathic cases of premature follicle depletion and improve ovarian health in reproductive‐age women.

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“…Granulosa cells, as key functional components of follicles, perform an initiating role in follicular atresia and further affect the reproductive facility [6][7][8]. Granulosa cell apoptosis appears to be an essential part of ovarian development, and it is a reflection of the mitogenic growth of the follicle [9]. Previous studies have elaborated that lipopolysaccharides (LPS) could induce an ovarian inflammatory response and affect ovarian development directly [10,11].…”

Section: Introductionmentioning

confidence: 99%

UFL1 Alleviates LPS-Induced Apoptosis by Regulating the NF-κB Signaling Pathway in Bovine Ovarian Granulosa Cells

Wang

et al. 2020

Biomolecules

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Ubiquitin-like modifier 1 ligating enzyme 1 (UFL1) is an E3 ligase of ubiquitin fold modifier 1 (UFM1), which can act together with its target protein to inhibit the apoptosis of cells. Lipopolysaccharides (LPS) can affect the ovarian health of female animals by affecting the apoptosis of ovarian granulosa cells. The physiological function of UFL1 on the apoptosis of bovine (ovarian) granulosa cells (bGCs) remains unclear; therefore, we focused on the modulating effect of UFL1 on the regulation of LPS-induced apoptosis in ovarian granulosa cells. Our study found that UFL1 was expressed in both the nucleus and cytoplasm of bGCs. The results here demonstrated that LPS caused a significant increase in the apoptosis level of bGCs in cows, and also dramatically increased the expression of UFL1. Furthermore, we found that UFL1 depletion caused a significant increase in apoptosis (increased the expression of BAX/BCL-2 and the activity of caspase-3). Conversely, the overexpression of UFL1 relieved the LPS-induced apoptosis. In order to assess whether the inhibition of bGCs apoptosis involved in the nuclear factor-κB (NF-κB) signaling pathway resulted from UFL1, we detected the expression of NF-κB p-p65. LPS treatment resulted in a significant upregulation in the protein concentration of NF-κB p-p65, and knockdown of UFL1 further increased the phosphorylation of NF-κB p65, while UFL1 overexpression significantly inhibited the expression of NF-κB p-p65. Collectively, UFL1 could suppress LPS-induced apoptosis in cow ovarian granulosa cells, likely via the NF-κB pathway. These results identify a novel role of UFL1 in the modulation of bGC apoptosis, which may be a potential signaling target to improve the reproductive health of dairy cows.

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Granulosa Cell Apoptosis in the Ovarian Follicle—A Changing View

Cited by 142 publications

References 97 publications

Clinical correlation of apoptosis in human granulosa cells—A review

Clinical correlation of apoptosis in human granulosa cells—A review

Pathways coordinating oocyte attrition and abundance during mammalian ovarian reserve establishment

UFL1 Alleviates LPS-Induced Apoptosis by Regulating the NF-κB Signaling Pathway in Bovine Ovarian Granulosa Cells

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