The interplay between oxidative stress, zinc, and metabolic dysfunction in polycystic ovarian syndrome.

Polycystic ovarian syndrome (PCOS) is a functional endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology that has been associated with chronic disease and comorbidities including adverse metabolic and cardiac disorders. This review aims to evaluate the role of oxidative stress and zinc in the metabolic dysfunction observed in PCOS, with a focus on insulin resistance. Recent studies indicate that oxidative stress markers are elevated in PCOS and correlate with hyperandrogenemia, obesity, and insulin resistance.

Chronological age enhances aging phenomena and protein nitration in oocyte.

Background: The average age of childbearing has increased over the years contributing to infertility, miscarriages, and chromosomal abnormalities largely invoked by an age-related decline in oocyte quality. In this study, we investigate the role of nitric oxide (NO) insufficiency and protein nitration in oocyte chronological aging.

Methods: Mouse oocytes were retrieved from young breeders (YB, 8-14 weeks [w]), retired breeders (RB, 48-52w) and old animals (OA, 80-84w) at 13.

A review of nitric oxide and oxidative stress in typical ovulatory women and in the pathogenesis of ovulatory dysfunction in PCOS.

Polycystic ovary syndrome (PCOS) is a heterogeneous functional endocrine disorder associated with a low-grade, chronic inflammatory state. Patients with PCOS present an increased risk of metabolic comorbidities and often menstrual dysregulation and infertility due to anovulation and/or poor oocyte quality. Multiple mechanisms including oxidative stress and low-grade inflammation are believed to be responsible for oocyte deterioration; however, the influence of nitric oxide (NO) insufficiency in oocyte quality and ovulatory dysfunction in PCOS is still a matter for debate.

Determinants of Embryo Implantation: Roles of the Endometrium and Embryo in Implantation Success.

Both uterine endometrium and embryo contribute to implantation success. However, their relative role in the implantation success is still a matter for debate, as are the roles of endometrial receptivity analysis (ERA), endometrial scratch (ES), endometrial microbiome, and intrauterine or intravenous measures that are currently advocated to improve the implantation success. There is insufficient evidence to suggest that the endometrium is more important than the embryo in determining the implantation success and the utility of these measures, especially when euploid embryos are transferred is limited.

The Implications of Insufficient Zinc on the Generation of Oxidative Stress Leading to Decreased Oocyte Quality.

Zinc is a transition metal that displays wide physiological implications ranging from participation in hundreds of enzymes and proteins to normal growth and development. In the reproductive tract of both sexes, zinc maintains a functional role in spermatogenesis, ovulation, fertilization, normal pregnancy, fetal development, and parturition. In this work, we review evidence to date regarding the importance of zinc in oocyte maturation and development, with emphasis on the role of key zinc-binding proteins, as well as examine the effects of zinc and reactive oxygen species (ROS) on oocyte quality and female fertility.

Diminishing oocyte quality with advancing age is associated with deficiency of nitric oxide synthase cofactors, tetrahydrobiopterin, and zinc, in mouse oocytes.

Objective: To study the implications of decreased zinc and tetrahydrobiopterin (HB) associated with chronological aging on oocyte quality using a mouse model. HB and zinc are essential cofactors for nitric oxide synthase (NOS), because they aid in electron transfer and dimeric stability, and their bioavailability is crucial in regulating NOS coupling. We have previously shown that sufficient levels of nitric oxide (NO) are essential for maintaining oocyte quality and activation, and NO levels decrease in the oocyte as a function of age.

Hypochlorous acid facilitates inducible nitric oxide synthase subunit dissociation: The link between heme destruction, disturbance of the zinc-tetrathiolate center, and the prevention by melatonin.

Inducible nitric oxide synthase (iNOS) is a zinc-containing hemoprotein composed of two identical subunits, each containing a reductase and an oxygenase domain. The reductase domain contains binding sites for NADPH, FAD, FMN, and tightly bound calmodulin and the oxygenase domain contains binding sites for heme, tetrahydrobiopterin (HB), and l-arginine. The enzyme converts l-arginine into nitric oxide (NO) and citrulline in the presence of O.

Melatonin interferes with COVID-19 at several distinct ROS-related steps.

Recent studies have shown a correlation between COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and the distinct, exaggerated immune response titled "cytokine storm". This immune response leads to excessive production and accumulation of reactive oxygen species (ROS) that cause clinical signs characteristic of COVID-19 such as decreased oxygen saturation, alteration of hemoglobin properties, decreased nitric oxide (NO) bioavailability, vasoconstriction, elevated cytokines, cardiac and/or renal injury, enhanced D-dimer, leukocytosis, and an increased neutrophil to lymphocyte ratio. Particularly, neutrophil myeloperoxidase (MPO) is thought to be especially abundant and, as a result, contributes substantially to oxidative stress and the pathophysiology of COVID-19.