Ilaria Palmieri

In recent decades, intensified human activities, including industrialization and urban expansion, have given rise to significant environmental challenges, with plastic pollution emerging as a critical concern. Microplastics, particularly those derived from polystyrene (PS-MPs), are widespread in soils and oceans, posing risks to biodiversity and human health through ingestion, inhalation, and contact. This study examined the detrimental impact of PS-MPs on Zebrafish-Danio rerio (Hamilton, 1822) erythrocytes. The zebrafish (Danio rerio) is a well-established model organism in biomedical research, whereas its erythrocytes served as the cellular model investigated in this study. In vitro experiments involved exposing zebrafish erythrocytes, isolated from 25 adult zebrafish, to 105 µg/mL of PS-MPs for 30, 60 and 90 min to assess cytotoxicity, genotoxicity and oxidative stress. The results revealed a time-dependent and statistically significant reduction in erythrocyte viability (−30% to −50%), genomic stability (%GTS −20% to −40%), and a concomitant increase in DNA damage (DFI ~30–38%) and ROS production (~27–35%) compared to controls (all p ≤ 0.05). These molecular disruptions related to reduced cell viability, indicating that PS-MPs are cytotoxic and genotoxic, causing genetic damage and oxidative imbalance. The results obtained confirmed the toxicity of PS-MPs. These data suggest that PS-MPs can interfere with genetic material by inducing apoptosis through oxidative imbalance.

Female infertility affects millions of women worldwide and is frequently caused by ovulatory disorders and uterine pathologies. Among these, endometrial abnormalities play a central role, especially in cases of embryo implantation failure during assisted reproductive techniques (ARTs). Endometrial receptivity, the period during which the endometrium prepares to receive and support embryo implantation, is a complex process regulated by essential morphological, molecular, and immunological changes necessary for a successful pregnancy. This review examines the mechanisms that govern endometrial receptivity and investigates the dysfunctions that may compromise this phase. In particular, it focuses on key biomarkers of receptivity, such as estrogen receptor-alpha (ERα), integrins, and uterine immune cells, which are crucial for endometrial preparation. It provides an in-depth understanding of female reproductive physiology and the main indicators to optimize embryo transfer at the most opportune time during the menstrual cycle within medically assisted reproductive techniques. Furthermore, it explores innovative approaches, such as immunomodulation and mesenchymal stem cell therapy, which are opening new diagnostic and therapeutic horizons, offering hope to many couples facing reproductive challenges.

The success of embryo implantation and pregnancy depends on a complex interaction between the trophoblast and the endometrial environment, where endometrial receptivity plays a crucial role in this process. Assisted reproductive technologies (ARTs) are essential in overcoming biological barriers and enabling implantation in women with fertility issues. However, one of the main challenges in ART is ensuring that the endometrium is receptive at the time of implantation. Therefore, identifying endometrial receptivity biomarkers is essential to optimize ART treatments, improving success rates. A comprehensive literature review was conducted by searching peer-reviewed articles published in PubMed, Scopus, and Web of Science databases. The search included studies focusing on molecular and cellular mechanisms underlying endometrial receptivity in both natural and stimulated cycles. Various experimental methods, including proteomic and microRNA studies, have identified key biomarkers involved in endometrial receptivity, such as adhesion molecules, growth factors, and others. However, ovarian stimulation in fertility treatments can alter endometrial receptivity, making approaches like frozen embryo transfer necessary. Despite advancements, many questions persist regarding the endometrial receptivity and implantation mechanisms in both natural and stimulated cycles. This article reviews the main molecules involved in endometrial receptivity in natural and stimulated cycles, highlighting their potential role as biomarkers for embryo implantation.

Polystyrene microplastics (PS-MPs) released in the environment reportedly affect the reproduction of various organisms, induced oxidative stress and apoptosis, resulting in altered sperm parameters. In this in vitro study, we tested the cytotoxicity and genotoxicity of PS-MPs by exposing human semen samples to PS-MPs levels (105 and 210 μg/mL) for 30–60–90 min. Semen parameters, genome stability, sperm DNA fragmentation (SDF) and reactive oxygen species (ROS) production were analyzed before and after exposure. Moreover, we also evaluated the expression level of spermatozoa-specific expressed genes essential for the fusion with oocyte (DCST1, DCST2, IZUMO1, SPACA6, SOF1, and TMEM95). After PS-MP exposure, semen concentration and morphology did not differ, while sperm vitality and motility decreased in a time-dependent manner. In addition, sperm agglutination was observed in the groups exposed to both PS-MPs concentrations tested. A time- and concentration-dependent reduction in genomic stability, as well as increased SDF and ROS production, was also observed. Moreover, all investigated transcripts were down-regulated after PS-MP exposure. Our results confirm the oxidative stress-mediated genotoxicity and cytotoxicity of PS-MPs on human spermatozoa. The sperm agglutination observed after treatment could be due to the aggregation of PS-MPs already adhered to the sperm membranes, hindering sperm movement and fertilizing capability. Interestingly, the downregulation of genes required for sperm–oocyte fusion, resulting from data on the in vitro experimental system, suggests that PS-MP exposure may have implications for sperm functionality. While these findings highlight potential mechanisms of sperm dysfunction, further investigations using in vivo models are needed to determine their broader biological implications. Possible environmental and working exposure to pollutants should be considered during the counselling for male infertility.

Polycyclic aromatic hydrocarbons (PAHs) are a group of organic compounds with fused aromatic rings, primarily derived from combustion processes and environmental pollutants. This narrative review discusses the most relevant studies on PAHs, focusing on their sources, environmental and occupational exposure, and effects on human health, emphasizing their roles as carcinogenic, mutagenic, and teratogenic agents. The primary pathways for human exposure to PAHs are through the ingestion of contaminated food (mainly due to some food processing methods, such as smoking and high-temperature cooking techniques), the inhalation of ambient air, and the smoking of cigarettes. Coke oven workers are recognized as a high-risk occupational group for PAH exposure, highlighting the need for appropriate strategies to mitigate these risks and safeguard worker health. PAHs are metabolized into reactive intermediates in the body, which can lead to DNA damage and promote the development of various health conditions, particularly in environments with high exposure levels. Chronic PAH exposure has been linked to respiratory diseases, as well as cardiovascular problems and immune system suppression. Furthermore, this review underscores the significant impact of PAHs on reproductive health. The results of the reported studies suggest that both male and female fertility can be compromised due to oxidative stress, DNA damage, and endocrine disruption caused by PAH exposure. In males, PAHs impair sperm quality, while, in females, they disrupt ovarian function, potentially leading to infertility, miscarriage, and birth defects. Fetal exposure to PAHs is also associated with neurodevelopmental disorders. Given the extensive and detrimental health risks posed by PAHs, this review stresses the importance of stringent environmental regulations, occupational safety measures, and public health initiatives to mitigate exposure and safeguard reproductive and overall health.

Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them arises. OS can damage cells and influence sperm production. High levels of lipid peroxidation have been linked to reduced sperm motility and decreased fertilization ability. This literature review discusses the most commonly used biomarkers to measure sperm damage caused by ROS, such as the high level of OS in seminal plasma as an indicator of imbalance in antioxidant activity. The investigated biomarkers include 8-hydroxy-2-deoxyguanosine acid (8-OHdG), a marker of DNA damage caused by ROS, and F2 isoprostanoids (8-isoprostanes) produced by lipid peroxidation. Furthermore, this review focuses on recent methodologies including the NGS polymorphisms and differentially expressed gene (DEG) analysis, as well as the epigenetic mechanisms linked to ROS during spermatogenesis along with new methodologies developed to evaluate OS biomarkers. Finally, this review addresses a valuable insight into the mechanisms of male infertility provided by these advances and how they have led to new treatment possibilities. Overall, the use of biomarkers to evaluate OS in male infertility has supplied innovative diagnostic and therapeutic approaches, enhancing our understanding of male infertility mechanisms.