Signal Transduction Pathways in Oocyte Maturation<sup>*</sup>

Richard, François J.; Santiquet, Nicolas; Bergeron, Annick; Khan, Daulat Raheem

doi:10.1002/9781118881286.ch8

Cited by 2 publications

(2 citation statements)

References 250 publications

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“…The functions that are mediated by cAMP include those that occur in ovarian follicular cells following the stimulation of the follicle-stimulating hormone (FSH) receptor 1 and the luteinizing hormone (LH) receptor 2 . These functions include steroidogenesis, folliculogenesis, cell division, ovulation, oocyte maturation, cumulus cell expansion and luteinisation 3 .…”

Section: Introductionmentioning

confidence: 99%

“…Several examples argue for PDEs sub-cellular localization. As such, PDE has been found in detergent-resistant membranes such as lipid rafts, and these membrane microdomains appear to play an essential role in proper signalling 15–18 . Anchoring proteins have been found in association with PDE in sub-cellular compartments such as the Golgi apparatus, the sarcoplasma, and mitochondria.…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Lounas

Vernoux

Germain

et al. 2019

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Cyclic adenosine monophosphate (cAMP) is a ubiquitous secondary messenger that plays a central role in endocrine tissue function, particularly in the synthesis of steroid hormones. The intracellular concentration of cAMP is regulated through its synthesis by cyclases and its degradation by cyclic nucleotide phosphodiesterases (PDEs). Although the expression and activity of PDEs impact the specificity and the amplitude of the cAMP response, it is becoming increasingly clear that the sub-cellular localization of PDE emphasizes the spatial regulation of the cell signalling processes that are essential for normal cellular function. We first examined the expression of PDE8A in porcine ovarian cells. PDE8A is expressed in granulosa cells, cumulus cells and oocytes. Second, we assessed the mitochondrial sub-cellular localization of PDE8A. Using western blotting with isolated mitochondrial fractions from granulosa cells and cumulus-oocyte complexes revealed immuno-reactive bands. PDE assay of isolated mitochondrial fractions from granulosa cells measured specific PDE8 cAMP-PDE activity as PF-04957325-sensitive. The immune-reactive PDE8A signal and MitoTracker labelling co-localized supporting mitochondrial sub-cellular localization of PDE8A, which was confirmed using immuno-electron microscopy. Finally, the effect of PDE8 on progesterone production was assessed during the in-vitro maturation of cumulus-oocyte complexes. Using PF-04957325, we observed a significant increase (P < 0.05) in progesterone secretion with follicle-stimulating hormone (FSH). Active mitochondria stained with MitoTracker orange CMTMRos were also increased by the specific PDE8 inhibitor supporting its functional regulation. In conclusion, we propose the occurrence of mitochondrial sub-cellular localization of PDE8A in porcine granulosa cells and cumulus cells. This suggests that there is potential for new strategies for ovarian stimulation and artificial reproductive technologies, as well as the possibility for using new media to improve the quality of oocytes.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Lounas

Vernoux

Germain

et al. 2019

Sci Rep

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Association between follicular fluid phthalate concentrations and extracellular vesicle microRNAs expression

et al. 2021

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STUDY QUESTION Are phthalate metabolite concentrations in follicular fluid (FF) associated with the expression of extracellular vesicle microRNAs (EV-miRNAs)? SUMMARY ANSWER Phthalate metabolite concentrations are associated with the expression of EV-miRNA and their associated pathways in FFs. WHAT IS KNOWN ALREADY Phthalate metabolites were recently detected in FF. Urinary phthalate metabolite concentrations alter the expression of EV-miRNAs in FF. STUDY DESIGN, SIZE, DURATION Prospective study including 105 women recruited between January 2014 and August 2016 in a tertiary university-affiliated hospital. PARTICIPANTS/MATERIALS, SETTING, METHODS We assessed FF concentrations of 12 phthalate metabolites. EV-miRNAs were isolated from aliquots of the same FF, and their expression profiles were measured using a human miRNA panel. Associations between EV-miRNAs that were present in >50% of the samples and phthalate metabolites that were measured in >74% of the FF samples were tested. Genes regulated by EV-miRNAs that were found to be significantly (false discovery rate q-value < 0.1) correlated with FF-phthalates were analyzed for pathways linked with female fertility using miRWalk2.0 Targetscan database, DAVID Bioinformatics Resources and Kyoto Encyclopedia of Genes and Genomes (KEGG). MAIN RESULTS AND THE ROLE OF CHANCE Of 12 phthalate metabolites, 11 were measured in at least one FF sample. Mono (6-COOH-2-methylheptyl) phthalate (MCOMHP), mono-2-ethyl-5-carboxypentyl phthalate (mECPP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono-isobutyl phthalate (MiBP), monoethyl phthalate (MEP) and mono (7-COOH-2-methyloctyl) phthalate (MCOMOP) were detected in more than 74% of the samples. Of 754 EV-miRNAs tested, 39 were significantly associated either with MEP, MBzP, MCOMOP, MCOMHP and/or with mECPP, after adjusting for multiple testing (P < 0.05). KEGG-based pathway enrichment analysis of the genes regulated by these miRNAs showed that these EV-miRNAs may be involved in pathways related to ovary or oocyte development, maturation and fertilization. LIMITATIONS, REASONS FOR CAUTION The use of miRNA panel array limits the number of potential relevant miRNAs. Moreover, several of the phthalate metabolites examined may be biased due to internal (enzymatic activity) or external (contamination in medical interventions) causes. WIDER IMPLICATIONS OF THE FINDINGS Phthalate metabolites may alter follicular EV-miRNAs profile and thus impair pathways that are involved with oocyte development, maturation and fertilization. Our results contribute to understanding of possible mechanism(s) in which endocrine disruptor chemicals interfere with female fertility. STUDY FUNDING/COMPETING INTERESTS This work was supported by the National Institutes of Environmental Health Sciences [Grant R21-ES024236]; and Environmental Health Fund, Israel [Grant 1301], no competing interests. TRIAL REGISTRATION NUMBER N/A.

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Signal Transduction Pathways in Oocyte Maturation^*

Cited by 2 publications

References 250 publications

Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Association between follicular fluid phthalate concentrations and extracellular vesicle microRNAs expression

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Signal Transduction Pathways in Oocyte Maturation*

Cited by 2 publications

References 250 publications

Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells

Association between follicular fluid phthalate concentrations and extracellular vesicle microRNAs expression

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Signal Transduction Pathways in Oocyte Maturation^*