The influence of in vivo exposure to nonylphenol ethoxylate 10 (NP-10) on the ovarian reserve in a mouse model.

AIM: To determine the effect of nonylphenol-ethoxylate-10 (NP-10) on the ovarian reserve in a mouse model. DESIGN: Female mice were maintained on purified water or exposed to NP-10 from 3-7-weeks of age. At 7-weeks they were stimulated, mated and the zygotes were cultured in-vitro. Three and 7-weeks old mice were untreated controls. Identical groups were sacrificed without stimulation. Ovaries were analysed for follicular composition. Respiratory-chain (RC) activity and reactive-oxygen-species (ROS) production were measured in brains and livers. RESULTS: Seven-weeks-old mice produced fewer oocytes/embryos than 3-week-old mice. At 7-weeks, mice exposed to NP-10 produced more oocytes/embryos the controls. Their ovaries contained more primordial/primary follicles, with a lower rate of proliferation and fewer antral follicles. There were no differences in follicular apoptosis, RC-activity or ROS production. CONCLUSIONS: In this model, exposure to NP-10 inhibited the spontaneous follicular recruitment, the first report of successful inhibition of physiologic ovarian aging, to the best of our knowledge.

The Relationship between Mitochondrial Respiratory Chain Activities in Muscle and Metabolites in Plasma and Urine: A Retrospective Study.

The relationship between 114 cases with decreased enzymatic activities of mitochondrial respiratory chain (MRC) complexes I-V (C I-V) in muscle and metabolites in urine and plasma was retrospectively examined. Less than 35% disclosed abnormal plasma amino acids and acylcarnitines, with elevated alanine and low free carnitine or elevated C4-OH-carnitine as the most common findings, respectively. Abnormal urine organic acids (OA) were detected in 82% of all cases. In CI and CII defects, lactic acid (LA) in combination with other metabolites was the most common finding. 3-Methylglutaconic (3MGA) acid was more frequent in CIV and CV, while Tyrosine metabolites, mainly 4-hydroxyphenyllactate, were common in CI and IV defects. Ketones were present in all groups but more prominent in combined deficiencies. There was a significant strong correlation between elevated urinary LA and plasma lactate but none between urine Tyrosine metabolites and plasma Tyrosine or urinary LA and plasma Alanine. All except one of 14 cases showed elevated FGF21, but correlation with urine OA was weak. Although this study is limited, we conclude that urine organic acid test in combination with plasma FGF21 determination are valuable tools in the diagnosis of mitochondrial diseases.

The Effects of Ascorbate, N-Acetylcysteine, and Resveratrol on Fibroblasts from Patients with Mitochondrial Disorders.

Reactive oxygen species (ROS) are assumed to be implicated in the pathogenesis of inborn mitochondrial diseases affecting oxidative phosphorylation (OXPHOS). In the current study, we characterized the effects of three small molecules with antioxidant properties (N-acetylcysteine, ascorbate, and resveratrol) on ROS production and several OXPHOS parameters (growth in glucose free medium, ATP production, mitochondrial content and membrane potential (MMP)), in primary fibroblasts derived from seven patients with different molecularly defined and undefined mitochondrial diseases. N-acetylcysteine appeared to be the most beneficial compound, reducing ROS while increasing growth and ATP production in some patients' cells. Ascorbate showed a variable positive or negative effect on ROS, ATP production, and mitochondrial content, while incubation with resveratrol disclosed either no effect or detrimental effect on ATP production and MMP in some cells. The individual responses highlight the importance of investigating multiple parameters in addition to ROS to obtain a more balanced view of the overall effect on OXPHOS when evaluating antioxidant treatment options for mitochondrial diseases.