Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled receptors (GPCR), GPR30, estrogen-related receptor (ERRγ) to activate estrogen signaling via downstream kinases. Bisphenol A, dichlorodiphenyltrichloroethane, dichlorodiphenyldichloroethylene, polychlorinated biphenyls and phthalates are major toxicants that interfere with the normal estrogen/androgen pathways leading to infertility in both sexes through many ways, including DNA damage in spermatozoids, altered methylation pattern, histone modifications and miRNA expression.

The average age of fathers at first pregnancy has risen significantly over the last decade owing to various variables, including a longer life expectancy, more access to contraception, later marriage, and other factors. As has been proven in several studies, women over 35 years of age have an increased risk of infertility, pregnancy problems, spontaneous abortion, congenital malformations, and postnatal issues. There are varying opinions on whether a father’s age affects the quality of his sperm or his ability to father a child. First, there is no single accepted definition of old age in a father. Second, much research has reported contradictory findings in the literature, particularly concerning the most frequently examined criteria. Increasing evidence suggests that the father’s age contributes to his offspring’s higher vulnerability to inheritable diseases. Our comprehensive literature evaluation shows a direct correlation between paternal age and decreased sperm quality and testicular function. Genetic abnormalities, such as DNA mutations and chromosomal aneuploidies, and epigenetic modifications, such as the silencing of essential genes, have all been linked to the father’s advancing years. Paternal age has been shown to affect reproductive and fertility outcomes, such as the success rate of in vitro fertilisation (IVF), intracytoplasmic sperm injection (ICSI), and premature birth rate. Several diseases, including autism, schizophrenia, bipolar disorders, and paediatric leukaemia, have been linked to the father’s advanced years. Therefore, informing infertile couples of the alarming correlations between older fathers and a rise in their offspring’s diseases is crucial, so that they can be effectively guided through their reproductive years.

Erectile dysfunction (ED) is a prevalent condition affecting men’s sexual health, with oxidative stress (OS) having recently been identified as a significant contributing causative factor. This narrative review aims to elucidate the role of OS in the pathophysiology of ED, focusing on impact, mechanisms, and potential therapeutic interventions. Key findings indicate that OS disrupts endothelial function and nitric oxide (NO) signaling, crucial for erectile function. Various sources of reactive oxygen species (ROS) and their detrimental effects on penile tissue are discussed, including aging, diabetes mellitus, hypertension, hyperlipidemia, smoking, obesity, alcohol consumption, psychological stress, hyperhomocysteinemia, chronic kidney disease, and sickle cell disease. Major sources of ROS, such as NADPH oxidase, xanthine oxidase, uncoupled endothelial NO synthase (eNOS), and mitochondrial electron transport, are identified. NO is scavenged by these ROS, leading to endothelial dysfunction characterized by reduced NO availability, impaired vasodilation, increased vascular tone, and inflammation. This ultimately results in ED due to decreased blood flow to penile tissue and the inability to achieve or maintain an erection. Furthermore, ROS impact the transmission of nitrergic neurotransmitters by causing the death of nitrergic neurons and reducing the signaling of neuronal NO synthase (nNOS), exacerbating ED. Therapeutic approaches targeting OS, including antioxidants and lifestyle modifications, show promise in ameliorating ED symptoms. The review underscores the need for further research to develop effective treatments, emphasizing the interplay between OS and vascular health in ED. Integrating pharmacological and non-pharmacological strategies could enhance clinical outcomes for ED patients, advocating for OS management in ED treatment protocols to improve patient quality of life.

Oxidative stress (OS), which arises through an imbalance between the formation of reactive oxygen species (ROS) and antioxidant defenses, plays a key role in the pathophysiology of female infertility, with the latter constituting just one of a number of diseases linked to OS as a potential cause. The aim of the present article is to review the literature regarding the association between OS and female infertility. Among the reproductive diseases considered are endometriosis and polycystic ovary syndrome (PCOS), while environmental pollutants, lifestyle variables, and underlying medical conditions possibly resulting in OS are additionally examined. Current evidence points to OS likely contributing to the pathophysiology of the above reproductive disorders, with the amount of damage done by OS being influenced by such variables as duration and severity of exposure and the individual’s age and genetic predisposition. Also discussed are the processes via which OS may affect female fertility, these including DNA damage and mitochondrial dysfunction. Finally, the last section of the manuscript contains an evaluation of treatment options, including antioxidants and lifestyle modification, capable of minimizing OS in infertile women. The prime message underlined by this review is the importance of considering OS in the diagnosis and treatment of female infertility. Further studies are, nevertheless required to identify the best treatment regimen and its ideal duration.

Background/Objectives: Inflammation, infections, and oxidative stress (OS) all have an impact on male infertility, which is a complicated, multifaceted illness. OS affects motility and fertilization capability. It accomplishes this through damaging sperm DNA, oxidizing proteins, and triggering lipid peroxidation. These effects occur due to an imbalance between reactive oxygen species (ROS) and antioxidant defenses. Methods: This review aims to evaluate the impact of oxidative stress and inflammation on male infertility by assessing recent literature. Results: Pro-inflammatory cytokines, like TNF-α and IL-6, interfere with spermatogenesis and promote oxidative damage. Additionally, infections caused by pathogens like Escherichia coli and Chlamydia trachomatis alter the reproductive microenvironment, leading to sperm dysfunction and inflammation. Conclusions: Early detection and targeted treatment are essential due to the intricate interactions among these elements. Microbiota-modulating techniques, antimicrobial therapies, anti-inflammatory drugs, and antioxidants are therapeutic approaches that may help reduce oxidative damage and enhance male fertility.