Obesity is gaining acceptance as a serious primary health burden that impairs the quality of life because of its associated complications, including diabetes, cardiovascular diseases, cancer, asthma, sleep disorders, hepatic dysfunction, renal dysfunction, and infertility. It is a complex metabolic disorder with a multifactorial origin. Growing evidence suggests that oxidative stress plays a role as the critical factor linking obesity with its associated complications. Obesity per se can induce systemic oxidative stress through various biochemical mechanisms, such as superoxide generation from NADPH oxidases, oxidative phosphorylation, glyceraldehyde auto-oxidation, protein kinase C activation, and polyol and hexosamine pathways. Other factors that also contribute to oxidative stress in obesity include hyperleptinemia, low antioxidant defense, chronic inflammation, and postprandial reactive oxygen species generation. In addition, recent studies suggest that adipose tissue plays a critical role in regulating the pathophysiological mechanisms of obesity and its related co-morbidities. To establish an adequate platform for the prevention of obesity and its associated health risks, understanding the factors that contribute to the cause of obesity is necessary. The most current list of obesity determinants includes genetic factors, dietary intake, physical activity, environmental and socioeconomic factors, eating disorders, and societal influences. On the basis of the currently identified predominant determinants of obesity, a broad range of strategies have been recommended to reduce the prevalence of obesity, such as regular physical activity, ad libitum food intake limiting to certain micronutrients, increased dietary intake of fruits and vegetables, and meal replacements. This review aims to highlight recent findings regarding the role of oxidative stress in the pathogenesis of obesity and its associated risk factors, the role of dysfunctional adipose tissue in development of these risk factors, and potential strategies to regulate body weight loss/gain for better health benefits.

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Obesity, Oxidative Stress, Adipose Tissue Dysfunction, and the Associated Health Risks: Causes and Therapeutic Strategies.

Intrauterine growth restriction (IUGR) is found in 1-10% of all pregnancies, and among women with risk factors even twice often. It is connected to worse obstetric results, and its complications can arise long time after delivery. In the paper we described etiology, diagnostics and monitoring of IUGR and its consequences for the child and for the course of neonatal periode.

Intrauterine growth restriction

https://www.fertstert.org/article/S0015-0282(14)02371-1/pdf

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

Because germline mutations are the source of all evolutionary adaptations and heritable diseases, characterizing their properties and the rate at which they arise across individuals is of fundamental importance for human genetics. After decades during which estimates were based on indirect approaches, notably on inferences from evolutionary patterns, it is now feasible to count de novo mutations in transmissions from parents to offspring. Surprisingly, this direct approach yields a mutation rate that is twofold lower than previous estimates, calling into question our understanding of the chronology of human evolution and raising the possibility that mutation rates have evolved relatively rapidly. Here, we bring together insights from studies of human genetics and molecular evolution, focusing on where they conflict and what the discrepancies tell us about important open questions. We begin by outlining various methods for studying the properties of mutations in humans. We review what we have learned from their applications about genomic factors that influence mutation rates and the effects of sex, age, and other sources of interindividual variation. We then consider the mutation rate as a product of evolution and discuss how and why it may have changed over time in primates.

https://www.annualreviews.org/doi/pdf/10.1146/annurev-genom-031714-125740

Determinants of Mutation Rate Variation in the Human Germline

Inadequate or excessive nutrient consumption leads to oxidative stress, which may disrupt oxidative homeostasis, activate a cascade of molecular pathways, and alter the metabolic status of various tissues. Several foods and consumption patterns have been associated with various cancers and approximately 30–35% of the cancer cases are correlated with overnutrition or malnutrition. However, several contradictory studies are available regarding the association between diet and cancer risk, which remains to be elucidated. Concurrently, oxidative stress is a crucial factor for cancer progression and therapy. Nutritional oxidative stress may be induced by an imbalance between antioxidant defense and pro-oxidant load due to inadequate or excess nutrient supply. Oxidative stress is a physiological state where high levels of reactive oxygen species (ROS) and free radicals are generated. Several signaling pathways associated with carcinogenesis can additionally control ROS generation and regulate ROS downstream mechanisms, which could have potential implications in anticancer research. Cancer initiation may be modulated by the nutrition-mediated elevation in ROS levels, which can stimulate cancer initiation by triggering DNA mutations, damage, and pro-oncogenic signaling. Therefore, in this review, we have provided an overview of the relationship between nutrition, oxidative stress, and cancer initiation, and evaluated the impact of nutrient-mediated regulation of antioxidant capability against cancer therapy.

Correlation between Oxidative Stress, Nutrition, and Cancer Initiation.

Oxidative stress (OS), a state characterized by an imbalance between pro-oxidant molecules including reactive oxygen and nitrogen species, and antioxidant defenses, has been identified to play a key role in the pathogenesis of subfertility in both males and females. The adverse effects of OS on sperm quality and functions have been well documented. In females, on the other hand, the impact of OS on oocytes and reproductive functions remains unclear. This imbalance between pro-oxidants and antioxidants can lead to a number of reproductive diseases such as endometriosis, polycystic ovary syndrome (PCOS), and unexplained infertility. Pregnancy complications such as spontaneous abortion, recurrent pregnancy loss, and preeclampsia, can also develop in response to OS. Studies have shown that extremes of body weight and lifestyle factors such as cigarette smoking, alcohol use, and recreational drug use can promote excess free radical production, which could affect fertility. Exposures to environmental pollutants are of increasing concern, as they too have been found to trigger oxidative states, possibly contributing to female infertility. This article will review the currently available literature on the roles of reactive species and OS in both normal and abnormal reproductive physiological processes. Antioxidant supplementation may be effective in controlling the production of ROS and continues to be explored as a potential strategy to overcome reproductive disorders associated with infertility. However, investigations conducted to date have been through animal or in vitro studies, which have produced largely conflicting results. The impact of OS on assisted reproductive techniques (ART) will be addressed, in addition to the possible benefits of antioxidant supplementation of ART culture media to increase the likelihood for ART success. Future randomized controlled clinical trials on humans are necessary to elucidate the precise mechanisms through which OS affects female reproductive abilities, and will facilitate further explorations of the possible benefits of antioxidants to treat infertility.

/pdf/the-effects-of-oxidative-stress-on-female-reproduction-a-285352e9d1.pdf

The effects of oxidative stress on female reproduction: a review

The placenta is a hemochorial organ, meaning that it is directly bathed by maternal blood. Favorable fetal growth depends on optimal placental evolution and development, as it represents the interface between the maternal and fetal environments. The placenta plays a crucial role in fetal nutrition, respiration, and hormone synthesis. Vasculogenesis and angiogenesis are essential for normal placental development and effective maternal-fetal exchange. The onset of maternal circulation to the placenta is associated with a burst of oxidative stress (OS). This OS can serve at a physiological level to trigger pathways of differentiation in the regulation of villous remodeling, trophoblastic invasion, and production of angiogenic factors. In excess, however, OS can lead to the development of complications involving the placenta, such as fetal loss, preeclampsia, and intrauterine growth restriction.

Placental Vascular Morphogenesis and Oxidative Stress

Oxidative stress (OS) occurs as a result of elevated levels of reactive oxygen species (ROS) which surpass the body’s antioxidant defenses. This shift in homeostatic balance may create an unstable environment for normal female physiology. Reactive oxygen species, which are generated during crucial oxygen consumption processes, are becoming increasingly abundant. Excessive ROS causes extensive cellular injury, such as damage to DNA, lipid membranes, and proteins. Adequate amounts of antioxidants maintain a steady state, which counterbalance ROS levels, thereby preventing OS. Infertility problems may be attributed to reproductive pathologies, leading to OS. In vitro techniques expose gametes and embryos to an excess of ROS without the enzymatic antioxidant protection normally present in vivo, creating an unfavorable environment. Oxidative stress, as a result of excessive ROS production, has also been implicated in some lifestyle factors.

Reactive Oxygen Species and Female Infertility 121

Both animals and humans are exposed to toxins in the environment that may influence the onset and progression of endometriosis. Human exposure occurs mainly through ingestion of contaminated foods. Dioxins encompass a group of environmental pollutants that act as endocrine disruptors through the aryl hydrocarbon receptor and disturb the body’s physiologic homeostatic mechanisms. Some have even been labeled as carcinogens. Human exposure to toxins is often unavoidable, but measures including a detailed history taken by clinicians and lifestyle changes can help detect and limit exposure and assist in the body’s detoxification processes. Growing evidence suggests a possible link between endometriosis and environmental pollutants. Environmental pollutants such as dioxins, organochlorine pesticides (OCPs), bisphenols and phthalates and their association with endometriosis are highlighted in this review along with the steps patients can take to avoid them. Even though results from studies remain contradictory, we can’t overlook the positive association between environmental toxicants and endometriosis as they are disruptors of endocrine and reproductive function. The literature reviewed in this section highlights the general pathogenesis of endometriosis and proposed theories regarding its etiology. Further, it will provide an updated discussion of the implications of environmental exposure to pollutants in the development of endometriosis.

Beena J. Premkumar

Papers

The effects of oxidative stress on female reproduction: a review

Placental Vascular Morphogenesis and Oxidative Stress

Reactive Oxygen Species and Female Infertility 121

Role of Environmental Pollutants in Endometriosis