The role of BH3-only proteins in apoptosis within the ovary

Hutt, Karla J.

doi:10.1530/rep-14-0422

Cited by 61 publications

(53 citation statements)

References 100 publications

(118 reference statements)

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“…It is believed that apoptosis is the major mechanism involved in follicular atresia. There are two apoptotic pathways in mammalian cells: the intrinsic pathway (also known as the mitochondrial control of apoptosis signaling pathway) and the extrinsic apoptotic pathway [43]. Several studies have suggested that germ cell apoptosis is mediated by the intrinsic apoptosis pathway [44], which is regulated by the relative levels and activities of pro- and anti-apoptotic members of the BCL2 protein family [43].…”

Section: Discussionmentioning

confidence: 99%

“…There are two apoptotic pathways in mammalian cells: the intrinsic pathway (also known as the mitochondrial control of apoptosis signaling pathway) and the extrinsic apoptotic pathway [43]. Several studies have suggested that germ cell apoptosis is mediated by the intrinsic apoptosis pathway [44], which is regulated by the relative levels and activities of pro- and anti-apoptotic members of the BCL2 protein family [43]. The expression of pro-apoptotic BH3-only genes ( Noxa, Bmf, Bid, Bik, Bad and Bim ), the pro-apoptotic effector protein gene ( Bax and Bak ), initiator caspases ( Caspase 8 and Caspase 9 ) and executioner caspase ( Caspase 3 ) were upregulated in the ovaries of miR-17-92 cKO female mice.…”

Section: Discussionmentioning

confidence: 99%

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Ablation of the MiR-17-92 MicroRNA Cluster in Germ Cells Causes Subfertility in Female Mice

Wang

Tian

et al. 2018

Cell Physiol Biochem

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Background/Aims: Oogenesis is a highly complex process that is intricately regulated by interactions of multiple genes and signaling molecules. However, the underlying molecular mechanisms are poorly understood. There is emerging evidence that microRNAs contribute to oogenesis. Here, we aimed to investigate the role of miR-17-92 cluster in regulating oogenesis. Methods: The miR-17-92 cluster was genetically ablated in germ cells of female mice by applying the Cre-loxp system for conditional gene knockout. Mating experiment, superovulation and histological analysis were used to assess the fertility of the model female mice. TUNEL assay was used to identify apoptotic cells in ovaries. The expression level of apoptosis- and follicular atresia- related genes was evaluated by qRT-PCR. Western blotting was performed to detect protein expression. Bioinformatics software and dual luciferase reporter assay were applied to predict and verify the target of miR-17-92 cluster. Results: Deletion of miR-17-92 cluster in germ cells of female mice caused increased oocyte degradation and follicular atresia, perturbed oogenesis, and ultimately led to subfertility. Genes involved in follicular atresia and the mitochondrial apoptotic pathway were obviously up-regulated. Furthermore, we verified that miR-19a regulated oogenesis at the post-transcriptional level by targeting Bmf in the ovaries of miR-17-92 cluster conditional knockout female mice. Conclusion: The miR-17-92 cluster is an important regulator of oogenesis. These findings will assist in better understanding the etiology of disorders in oogenesis and in developing new therapeutic targets for female infertility.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Ablation of the MiR-17-92 MicroRNA Cluster in Germ Cells Causes Subfertility in Female Mice

Wang

Tian

et al. 2018

Cell Physiol Biochem

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“…34 Previous studies have demonstrated that both pathways are involved in GCs apoptosis. 26,35 However, as shown in the present study, we found that GC apoptosis driven by EGR1 overexpression induced hallmarks of mitochondrial apoptosis (BCL2, CAS-PASE-9 and CASPASE-3).…”

Section: Up-regulation Of Egr1 Induces P53 But Not Pten Activationmentioning

confidence: 99%

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

et al. 2016

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Follicular atresia is the main process responsible for the loss of follicles and oocytes from the ovary, and it is the root cause of ovarian aging. Apoptosis of granulosa cells (GCs) is the cellular mechanism responsible for follicular atresia in mammals. Recent advances have highlighted fundamental roles for EGR1 in agerelated diseases via the induction of apoptosis. In the present study, we found that the expression of EGR1 was significantly increased in aged mouse ovaries compared with young ovaries. Immunohistochemical analysis revealed strongly positive EGR1 staining in atretic follicles, especially in apoptotic granulosa cells. We further showed that EGR1 up-regulation in mouse primary granulosa cells inhibited cell proliferation and promoted apoptosis. In addition, the promotion of apoptosis in GCs by EGR1 increases over time and with reactive oxygen species (ROS) stimulation. Our mechanistic study suggested that EGR1 regulates GC apoptosis in a mitochondria-dependent manner and that this mainly occurs through the NF-kB signaling pathway. In conclusion, our results suggested that age-related up-regulation of EGR1 promotes GC apoptosis in follicle atresia during ovarian aging.

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“…By the time of birth, somatic pre-granulosa cells within the ovary have surrounded oocytes to generate primordial follicles, each consisting of one oocyte (~15 μm diameter in the mouse) enclosed by a single layer of squamous granulosa cells (Findlay et al 2015;Grive and Freiman 2015;Jorgensen 2013;Pepling 2012). However, for reasons not yet fully understood, a significant proportion of the oocyte population is lost by apoptosis during late embryogenesis (Ene et al 2013;Hutt 2015;Malki et al 2014), reducing the number of primordial follicles that form or remain at birth. Primordial follicles thus constitute the ovarian reserve pool, from which follicles are continually recruited during reproductive life into the growth phase to produce fertilizable eggs.…”

Section: Overview Of Oogenesis and Folliculogenesismentioning

confidence: 99%

Control of Oocyte Growth and Development by Intercellular Communication Within the Follicular Niche

El‐Hayek

Clarke

2016

Results and Problems in Cell Differentiation

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In the mammalian ovary, each oocyte grows and develops within its own structural and developmental niche-the follicle. Together with the female germ cell in the follicle are somatic granulosa cells, specialized companion cells that surround the oocyte and provide support to it, and an outer layer of thecal cells that serve crucial roles including steroid synthesis. These follicular compartments function as a single physiological unit whose purpose is to produce a healthy egg, which upon ovulation can be fertilized and give rise to a healthy embryo, thus enabling the female germ cell to fulfill its reproductive potential. Beginning from the initial stage of follicle formation and until terminal differentiation at ovulation, oocyte and follicle growth depend absolutely on cooperation between the different cellular compartments. This cooperation synchronizes the initiation of oocyte growth with follicle activation. During growth, it enables metabolic support for the follicle-enclosed oocyte and allows the follicle to fulfill its steroidogenic potential. Near the end of the growth period, intra-follicular interactions prevent the precocious meiotic resumption of the oocyte and ensure its nuclear differentiation. Finally, cooperation enables the events of ovulation, including meiotic maturation of the oocyte and expansion of the cumulus granulosa cells. In this chapter, we discuss the cellular interactions that enable the growing follicle to produce a healthy oocyte, focusing on the communication between the germ cell and the surrounding granulosa cells.

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The role of BH3-only proteins in apoptosis within the ovary

Cited by 61 publications

References 100 publications

Ablation of the MiR-17-92 MicroRNA Cluster in Germ Cells Causes Subfertility in Female Mice

Ablation of the MiR-17-92 MicroRNA Cluster in Germ Cells Causes Subfertility in Female Mice

Age-associated up-regulation of EGR1 promotes granulosa cell apoptosis during follicle atresia in mice through the NF-κB pathway

Control of Oocyte Growth and Development by Intercellular Communication Within the Follicular Niche

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