Non‐esterified fatty acid‐associated ability of follicular fluid to support porcine oocyte maturation and development

Ogawa, Kokichi; Itami, Nobuhiko; Ueda, Mitsutoshi; Kansaku, Kazuki; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

doi:10.1002/rmb2.12084

Cited by 14 publications

(15 citation statements)

References 31 publications

(73 reference statements)

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“…Thus, basal rates of respiration and glycolysis in GCs from the control group were significantly reduced in the presence of FF from older women but FF from the young donors fail to improve the bioenergetic parameters in the ARA group (Figure 3). Recently, a porcine in-vitro maturation model showed that supplementing the maturation medium with FF not only increased mitochondrial DNA copy number and the ATP content in both oocytes and cumulus cells, but also the survival of cumulus cells and the blastulation rate (Ogawa et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Reproductive senescence impairs the energy metabolism of human luteinized granulosa cells

Cecchino¹,

García-Velasco²,

Rial³

2021

Reproductive BioMedicine Online

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RESEARCH QUESTION: Female age is the single greatest factor influencing reproductive performance and granulosa cells are considered as potential biomarkers of oocyte quality. Is there an age-effect on the energy metabolism of human mural granulosa cells? DESIGN: Observational prospective cohort and experimental study including 127 women that underwent in vitro fertilization cycles. Women were allocated to two groups: a group of infertile patients aged over 38 years and a control group comprising oocyte donors aged less than 35 years.Individuals with pathologies that could impair fertility were excluded from both groups. Following oocyte retrieval, cumulus and granulosa cells were isolated and their bioenergetic properties (oxidative phosphorylation parameters, rate of aerobic glycolysis and adenine nucleotide levels) were analyzed and compared. RESULTS:Human mural luteinized granulosa and cumulus cells present high rates of aerobic glycolysis that cannot be increased further when mitochondrial ATP synthesis is inhibited. Addition of follicular fluid to the experimental media is necessary to reach the full respiratory capacity of the cells. Granulosa cells from aged women present lower mitochondrial respiration, although mitochondrial mass is not decreased, and lower aerobic glycolysis than those from young donors. The concurrent decrease in the two energy supply pathways leads to a decrease in the cellular ATP levels. CONCLUSIONS:Human mural luteinized granulosa cells exhibit a reduction in their energy metabolism as women age that is likely to influence female reproductive potential.

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Section: Discussionmentioning

confidence: 99%

Reproductive senescence impairs the energy metabolism of human luteinized granulosa cells

Cecchino¹,

García-Velasco²,

Rial³

2021

Reproductive BioMedicine Online

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“…Many studies reported that fatty acids are ligands for PPARs to transcribe genes for mitochondrial fatty acid oxidation, and PPAR inhibition reduces fatty acid oxidation as well as lipolysis [8,42]. Furthermore, elevated concentrations of non-esterified fatty acids and glucose enhance lipid contents and reduce lipolysis and fatty acid β-oxidation [43,44]. Increased lipid contents were correlated with apoptosis in blastocysts [38].…”

Section: Discussionmentioning

confidence: 99%

The PPARδ Agonist GW501516 Improves Lipolytic/Lipogenic Balance through CPT1 and PEPCK during the Development of Pre-Implantation Bovine Embryos

Idrees

Sheikh

et al. 2019

IJMS

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The PPARs (peroxisome proliferator-activated receptors) play critical roles in the regulation of lipid and glucose metabolism. PPARδ, a member of the PPARs family, is associated with decreased susceptibility to ectopic lipid deposition and is implicated in the regulation of mitochondrial processes. The current study aimed to determine the role of PPARδ in fatty acid β-oxidation and its influence on PEPCK for the lipogenic/lipolytic balance during in vitro bovine oocyte maturation and embryo development. Activation of PPARδ by GW501516, but not 2-BP, was indicated by intact embryonic PEPCK (cytosolic) and CPT1 expression and the balance between free fatty acids and mitochondrial β-oxidation that reduced ROS and inhibited p-NF-κB nuclear localization. Genes involved in lipolysis, fatty acid oxidation, and apoptosis showed significant differences after the GW501516 treatment relative to the control- and 2-BP-treated embryos. GSK3787 reversed the PPARδ-induced effects by reducing PEPCK and CPT1 expression and the mitochondrial membrane potential, revealing the importance of PPARδ/PEPCK and PPARδ/CPT1 for controlling lipolysis during embryo development. In conclusion, GW501516-activated PPARδ maintained the correlation between lipolysis and lipogenesis by enhancing PEPCK and CPT1 to improve bovine embryo quality.

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“…Thus, basal rates of respiration and glycolysis in GCs from the control group were significantly reduced in the presence of FF from older women but FF from the young donors fail to improve the bioenergetic parameters in the ARA group (Figure 3). Recently, a porcine in-vitro maturation model showed that supplementing the maturation medium with FF not only increased the mitochondrial DNA copy number and the ATP content in both oocytes and cumulus cells, but also the survival of cumulus cells and the blastulation rate [53].…”

Section: Discussionmentioning

confidence: 99%

Reproductive Senescence Impairs the Energy Metabolism of Human Granulosa Cells

Cecchino

Garcia-Velasco

Rial

2021

Preprint

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Female age is the single greatest factor influencing reproductive performance. It is widely known that mitochondrial dysfunction plays a key role in reproductive senescence. Ovarian bioenergetics includes a sophisticated metabolic synergism between oocytes and human mural granulosa cells (GCs), which is crucial for oocyte maturation during follicular growth. These cells are believed to be potential biomarkers of oocyte quality. It has been proposed that alterations in their energy metabolism could lead to infertility. We investigated if there is an age-related effect on the energy metabolism of human mural granulosa cells. We performed an observational prospective cohort and experimental study including 127 women that underwent in vitro fertilization cycles allocated to two groups: a control group comprising oocyte donors aged less than 35 years and a group of infertile women aged over 38 years. The bioenergetics of cumulus cells and purified mural GCs were determined from oxidative phosphorylation parameters, aerobic glycolysis and adenine nucleotide levels. We have found that human mural GCs and cumulus cells present a high glycolytic profile and that the follicular fluid is critical to sustain their energy metabolism. GCs from older women present lower mitochondrial respiration and glycolysis than those from young donors which is not accompanied by a lower respiratory capacity. The diminished energy metabolism leads to a decrease in the total cellular energy charge. We conclude that, as women age, mural granulosa cells exhibit a reduction in their energy metabolism that is likely to influence female reproductive potential.

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Non‐esterified fatty acid‐associated ability of follicular fluid to support porcine oocyte maturation and development

Cited by 14 publications

References 31 publications

Reproductive senescence impairs the energy metabolism of human luteinized granulosa cells

Reproductive senescence impairs the energy metabolism of human luteinized granulosa cells

The PPARδ Agonist GW501516 Improves Lipolytic/Lipogenic Balance through CPT1 and PEPCK during the Development of Pre-Implantation Bovine Embryos

Reproductive Senescence Impairs the Energy Metabolism of Human Granulosa Cells

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