Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

Leroy, Jo; Meulders, B.; Moorkens, Kerlijne; Xhonneux, I; Slootmans, J; Keersmaeker, Luc De; Smits, A; Pascottini, Osvaldo Bogado; Marei, Waleed F.A.

doi:10.1071/rd22204

Cited by 10 publications

(12 citation statements)

References 194 publications

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“…Oocyte development in a lipotoxic environment is thought to be one of the main negative effects of maternal obesity on fertility, as it promotes direct impairment of oocyte quality because of lipid accumulation and metabolic and oxidative stress 67 . In the present study, oocyte aerobic and anaerobic metabolism were significantly higher in OB than in NW mares, suggesting increased oocyte metabolic activity associated with obesity.…”

Section: Discussionmentioning

confidence: 99%

Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation

Catandi,

Fresa,

Cheng

et al. 2024

Sci Rep

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Obesity is a growing concern in human and equine populations, predisposing to metabolic pathologies and reproductive disturbances. Cellular lipid accumulation and mitochondrial dysfunction play an important role in the pathologic consequences of obesity, which may be mitigated by dietary interventions targeting these processes. We hypothesized that obesity in the mare promotes follicular lipid accumulation and altered mitochondrial function of oocytes and granulosa cells, potentially contributing to impaired fertility in this population. We also predicted that these effects could be mitigated by dietary supplementation with a combination of targeted nutrients to improve follicular cell metabolism. Twenty mares were grouped as: Normal Weight [NW, n = 6, body condition score (BCS) 5.7 ± 0.3], Obese (OB, n = 7, BCS 7.7 ± 0.2), and Obese Diet Supplemented (OBD, n = 7, BCS 7.7 ± 0.2), and fed specific feed regimens for ≥ 6 weeks before sampling. Granulosa cells, follicular fluid, and cumulus-oocyte complexes were collected from follicles ≥ 35 mm during estrus and after induction of maturation. Obesity promoted several mitochondrial metabolic disturbances in granulosa cells, reduced L-carnitine availability in the follicle, promoted lipid accumulation in cumulus cells and oocytes, and increased basal oocyte metabolism. Diet supplementation of a complex nutrient mixture mitigated most of the metabolic changes in the follicles of obese mares, resulting in parameters similar to NW mares. In conclusion, obesity disturbs the equine ovarian follicle by promoting lipid accumulation and altering mitochondrial function. These effects may be partially mitigated with targeted nutritional intervention, thereby potentially improving fertility outcomes in the obese female.

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Section: Discussionmentioning

confidence: 99%

Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation

Catandi,

Fresa,

Cheng

et al. 2024

Sci Rep

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“…Nevertheless, controlling chronic low-grade inflammation and fibrosis in the ovary would represent a novel therapeutic strategy to improve the follicular microenvironment. Animal models have indicated that antioxidants ( 27 , 51 ), insulin-sensitizing drugs ( 125 ), anti-aging drugs (senolytics) ( 126 ), immune checkpoint inhibitors ( 127 ), and antifibrosis drugs ( 125 ) may help minimize follicular depletion and oocyte quality decline. However, further studies are required to determine whether these drugs overcome ovarian dysfunction in PCOS, endometriosis, and aging.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, high ROS levels and low antioxidant capacity in follicular fluids were associated with poor pregnancy outcomes in human-assisted reproductive technology (ART) ( 49 , 50 ). Maternal conditions, including polycystic ovary syndrome (PCOS), endometriosis, and aging, may compromise the ovarian microenvironment ( 47 , 48 , 51 ). Therefore, the following sections discuss whether and how chronic low-grade inflammation negatively impacts ovarian function in PCOS, endometriosis, and aging.…”

Section: Pro-inflammatory Cytokines and Follicular Developmentmentioning

confidence: 99%

Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging

Orisaka,

Mizutani,

Miyazaki

et al. 2023

Front. Endocrinol.

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The ovarian microenvironment is critical for follicular development and oocyte maturation. Maternal conditions, including polycystic ovary syndrome (PCOS), endometriosis, and aging, may compromise the ovarian microenvironment, follicular development, and oocyte quality. Chronic low-grade inflammation can induce oxidative stress and tissue fibrosis in the ovary. In PCOS, endometriosis, and aging, pro-inflammatory cytokine levels are often elevated in follicular fluids. In women with obesity and PCOS, hyperandrogenemia and insulin resistance induce ovarian chronic low-grade inflammation, thereby disrupting follicular development by increasing oxidative stress. In endometriosis, ovarian endometrioma-derived iron overload can induce chronic inflammation and oxidative stress, leading to ovarian ferroptosis and fibrosis. In inflammatory aging (inflammaging), senescent cells may secrete senescence-associated secretory phenotype factors, causing chronic inflammation and oxidative stress in the ovary. Therefore, controlling chronic low-grade inflammation and fibrosis in the ovary would present a novel therapeutic strategy for improving the follicular microenvironment and minimizing ovarian dysfunction.

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“…gestational diabetes and miscarriage) 2 , 3 . The detrimental effects of maternal obesity are evident at the level of the oocyte and early embryo 4 . This was confirmed in a study where pregnancy rates were restored in obese women when donor oocytes from healthy mothers were used 5 .…”

Section: Introductionmentioning

confidence: 99%

Effect of lipotoxicity on mitochondrial function and epigenetic programming during bovine in vitro embryo production

Meulders,

Marei,

Xhonneux

et al. 2023

Sci Rep

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Maternal metabolic disorders may cause lipotoxic effects on the developing oocyte. Understanding the timing at which this might disrupt embryo epigenetic programming and how this is linked with mitochondrial dysfunction is crucial for improving assisted reproductive treatments, but has not been investigated before. Therefore, we used a bovine in vitro model to investigate if pathophysiological palmitic acid (PA) concentrations during in vitro oocyte maturation and in vitro embryo culture alter embryo epigenetic patterns (DNA methylation (5mC) and histone acetylation/methylation (H3K9ac/H3K9me2)) compared to control (CONT) and solvent control (SCONT), at the zygote and morula stage. Secondly, we investigated if these epigenetic alterations are associated with mitochondrial dysfunction and changes in ATP production rate, or altered expression of epigenetic regulatory genes. Compared to SCONT, H3K9ac and H3K9me2 levels were increased in PA-derived zygotes. Also, 5mC and H3K9me2 levels were increased in PA-exposed morulae compared to SCONT. This was associated with complete inhibition of glycolytic ATP production in oocytes, increased mitochondrial membrane potential and complete inhibition of glycolytic ATP production in 4-cell embryos and reduced SOD2 expression in PA-exposed zygotes and morulae. For the first time, epigenetic alterations in metabolically compromised zygotes and morulae have been observed in parallel with mitochondrial dysfunction in the same study.

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Maternal metabolic health and fertility: we should not only care about but also for the oocyte!

Cited by 10 publications

References 194 publications

Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation

Follicular metabolic alterations are associated with obesity in mares and can be mitigated by dietary supplementation

Chronic low-grade inflammation and ovarian dysfunction in women with polycystic ovarian syndrome, endometriosis, and aging

Effect of lipotoxicity on mitochondrial function and epigenetic programming during bovine in vitro embryo production

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