Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome

Chappell, Neil; Zhou, Beth; Hosseinzadeh, Pardis; Schutt, Amy K.; Gibbons, William E.; Selvanesan, Blesson Chellakkan

doi:10.1016/j.xfss.2020.12.001

Cited by 16 publications

(28 citation statements)

References 64 publications

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“…The genomic DNA was stored at −80 °C for subsequent use. Mitochondrial DNA copy number was assessed as previously described [ 31 , 32 ]. The qPCR was performed with 1:100 of diluted DNA templates for mitochondrially encoded cytochrome c oxidase 1, 2, and 3 and compared with genomically encoded reference gene, tubulin.…”

Section: Methodsmentioning

confidence: 99%

Prenatal Low-Protein Diet Affects Mitochondrial Structure and Function in the Skeletal Muscle of Adult Female Offspring

et al. 2022

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Gestational low-protein (LP) diet leads to glucose intolerance and insulin resistance in adult offspring. We had earlier demonstrated that LP programming affects glucose disposal in females. Mitochondrial health is crucial for normal glucose metabolism in skeletal muscle. In this study, we sought to analyze mitochondrial structure, function, and associated genes in skeletal muscles to explore the molecular mechanism of insulin resistance LP-programmed female offspring. On day four of pregnancy, rats were assigned to a control diet containing 20% protein or an isocaloric 6% protein-containing diet. Standard laboratory diet was given to the dams after delivery until the end of weaning and to pups after weaning. Gestational LP diet led to changes in mitochondrial ultrastructure in the gastrocnemius muscles, including a nine-fold increase in the presence of giant mitochondria along with unevenly formed cristae. Further, functional analysis showed that LP programming caused impaired mitochondrial functions. Although the mitochondrial copy number did not show significant changes, key genes involved in mitochondrial structure and function such as Fis1, Opa1, Mfn2, Nrf1, Nrf2, Pgc1b, Cox4b, Esrra, and Vdac were dysregulated. Our study shows that prenatal LP programming induced disruption in mitochondrial ultrastructure and function in the skeletal muscle of female offspring.

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Section: Methodsmentioning

confidence: 99%

Prenatal Low-Protein Diet Affects Mitochondrial Structure and Function in the Skeletal Muscle of Adult Female Offspring

et al. 2022

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“…In addition, the dynamic aggregation of microfilaments, which is essential for cortical polarization and MII phase asymmetric spindle localization, was observed being disrupted in oocytes. Mitochondrion was one of the primary organelle marker of oocyte quality, dysfunction of which might be due to age (Udagawa et al, 2014), metabolic disorders such as obesity (Wu et al, 2015), diabetes (Li et al, 2018), and polycystic ovary syndrome (Chappell et al, 2021). In the present study, mitochondria were affected by PA in a dose‐dependent manner that would influence oocyte maturation, fertilization, and developmental capacity (El Shourbagy et al, 2006; Santos et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Astaxanthin alleviates palmitic acid‐induced hindrance of porcine oocyte maturation

Wang

Zhu

et al. 2022

Reprod Domestic Animals

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Increased palmitic acid (PA) levels have been found in females with reduced fertility due to metabolic disorders. However, effective antioxidant astaxanthin (AXE) might positively affect animal reproduction. Therefore, the present study was designed to evaluate the impact of a high concentration of PA on oocyte maturation and the possible protective effect of AXE against high PA concentration in pigs. Firstly, different concentrations (0.2, 0.5, 0.8 mM) of PA were conducted on in vitro maturation (IVM) of pig oocytes (PA0.2, PA0.5, and PA0.8), while no addition of PA was performed as the control group (Ctrl). Results showed that the cumulus cell expansion index (CCEI) was lower in PA0.5 and PA0.8 groups compared to Ctrl group (p < .05). In PA0.5 group, not only did the percentage of matured oocytes with the first polar body (PB1) reduced, that with more oocytes arrested at germinal vesicle (GV) stage (53.44% ± 7.16% vs. 20.93% ± 5.16%, p < .05), but also a higher number of transzonal projections (TZPs) was observed in PA0.5 than Ctrl group. Besides, supplement of PA resulted in a dose‐dependent decrease in mitochondrial activity. Although no difference of lipid content was observed between PA0.5 and Ctrl groups, the lipid content was at a higher level in PA0.2 group than in the other three groups. Hence, concentration of 0.5 mM of PA was performed in the following experiments, and 2.5 μM AXE carried out to investigate the possible relief effects of PA (PA0.5 + AXE). Results showed that the percentage of matured oocytes with PB1 was higher in PA0.5 + AXE than in PA0.5 group (63.43% ± 1.50% vs. 55.33% ± 0.81%, p < .01), and ROS levels both in oocytes and their cumulus cells (CCs) reduced in PA0.5 + AXE when compared to PA0.5 group. In addition, the rate of CCs with apoptosis decreased in PA0.5 + AXE, and the expression level of caspase 3 and BAX was lower than PA0.5 group. In conclusion, the maturation of pig oocytes was inhibited by the high concentration of PA; however, this negative effect of PA‐induced might be relieved by the supplement of AXE.

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“…On the other hand, aromatase function is defective in PCOS [52]. Mitochondrial dysfunction has also been observed in PCOS following increased androgens and insulin resistance [53][54][55].…”

Section: Discussionmentioning

confidence: 99%

Association of Prx4, Total Oxidant Status, and Inflammatory Factors with Insulin Resistance in Polycystic Ovary Syndrome

Mazloomi

Sheikh

Farimani

et al. 2021

International Journal of Endocrinology

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Introduction. Chronic inflammation and oxidative stress conditions have been reported in women with polycystic ovary syndrome (PCOS). Peroxiredoxin 4 (Prx4) is a related antioxidant in insulin synthesis. We hypothesized that insulin resistance in these women is associated with total oxidant status (TOS) and inflammatory factors. Materials and Methods. Two hundred three people including 104 PCOS patients and 99 healthy women, who were matched for age and body mass index (BMI), entered the study. Waist circumference of the participants was measured; serum glucose, lipid profile, insulin, Prx4, TOS, hs-CRP, and TNF-α were also evaluated. Results. The Prx4 level was significantly lower in PCOS than in the control group. In addition, marked increase was observed in the concentration of TOS, hs-CRP, and TNF-α in PCOS, compared to the healthy women. There was a positive correlation of TOS with hs-CRP, TNF-α, and HOMA-IR. The risk of PCOS for subjects with high hs-CRP was 60 times greater than those who had low serum hs-CRP concentration; after performing multiple logistic regression analyses with the backward method, TNF-α was considered as an effective biomarker to predict PCOS β = 49.087 (all p < 0.05 ). Conclusion. This study identified increased oxidative stress and inflammation in PCOS; this may be due to decrease in the antioxidants, such as Prx4.

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Hyperandrogenemia alters mitochondrial structure and function in the oocytes of obese mouse with polycystic ovary syndrome

Cited by 16 publications

References 64 publications

Prenatal Low-Protein Diet Affects Mitochondrial Structure and Function in the Skeletal Muscle of Adult Female Offspring

Prenatal Low-Protein Diet Affects Mitochondrial Structure and Function in the Skeletal Muscle of Adult Female Offspring

Astaxanthin alleviates palmitic acid‐induced hindrance of porcine oocyte maturation

Association of Prx4, Total Oxidant Status, and Inflammatory Factors with Insulin Resistance in Polycystic Ovary Syndrome

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