Oxidative stress (OS) is a critical regulator of placental development; however, its specific effects on trophoblast biology remain incompletely elucidated. This narrative review synthesizes evidence derived from studies using human placental tissues and trophoblast cell models to delineate how excessive reactive oxygen species (ROS) disrupt molecular and cellular pathways essential for normal placentation. The literature search was restricted to human-based and in vitro investigations. Across these studies, OS was consistently shown to impair mitochondrial function in trophoblasts, resulting in increased mitochondrial ROS generation, loss of mitochondrial membrane potential, and activation of apoptotic signaling cascades. These mitochondrial disturbances were associated with reduced trophoblast proliferation, migration, and invasion, as well as dysregulation of angiogenic balance. Furthermore, several studies reported alterations in mitophagy, involvement of redox-sensitive pathways such as CYP1A1 and KLF9, and the extracellular release of mitochondrial DNA, which was linked to reduced cell viability and increased necrotic cell death. Collectively, the available evidence indicates that OS interferes with key trophoblast-dependent developmental processes, providing mechanistic insight into the pathogenesis of placental dysfunction observed in pregnancy complications such as preeclampsia (PE) and intrauterine growth restriction (IUGR). Elucidation of these pathways may inform the development of targeted therapeutic strategies aimed at preserving placental function and improving adverse pregnancy outcomes.

Cellular senescence, mitochondrial dysfunction, and cumulative oxidative stress (OS) are the main causes of the progressive decreases in oocyte and sperm quality that define reproductive age. There is growing evidence that these processes are controlled by systemic variables, such as metabolites produced from the gut microbiome and extracellular vesicle (EV)-mediated intercellular communication, rather than being exclusively regulated at the tissue level. Antioxidant enzymes, regulatory microRNAs, and bioactive lipids that regulate mitochondrial redox balance, mitophagy, and inflammatory signaling are transported by EVs derived from reproductive organs, stem cells, immune cells, and the gut microbiota. Concurrently, microbiome-derived metabolites such as urolithin A, short-chain fatty acids, and polyphenol derivatives enhance mitochondrial quality control, activate antioxidant pathways, and suppress senescence-associated secretory phenotypes. This narrative review integrates the most recent research on the relationship between redox homeostasis, mitochondrial function, gut microbiota activity, and EV signaling in the context of male and female reproductive aging. We propose an emerging gut–EV–mitochondria axis as a unified framework through which systemic metabolic and antioxidant signals affect gamete competence, reproductive tissue function, and fertility longevity. Finally, we discuss therapeutic implications, including microbiome modulation, EV-based interventions, and senotherapeutic strategies, highlighting key knowledge gaps and future research directions necessary for clinical translation.

Background/Objectives: Fetal growth restriction (FGR), formerly known as intrauterine growth retardation (IUGR), is defined as a fetus’ failure to reach its genetically predetermined growth potential. FGR has also been implicated in the development of autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), though strong supporting literature has yet to be published. This study aims to review the existing associations between FGR and autism spectrum disorder or attention-deficit hyperactivity disorder as studied in relevant literature, as well as the mechanisms that provide explanation of that association. Methods: We used a combination of the terms ‘Autism spectrum disorder’ OR ‘Attention deficit hyperactivity disorder’ OR ‘neurodevelopmental disorders’ AND ‘intrauterine growth retardation (IUGR)’ OR ‘fetal growth restriction (FGR)’ in an electronic search of PubMed/MEDLINE and Scopus databases. Results: After evaluating the existing literature, we found only a few studies assessed the risk of developing ASD or ADHD in IUGR/FGR children. Neurodevelopmental disorders have generally been linked to very low birth weight, small for gestational age neonates (SGA), prematurity, somatic mutations, and intrauterine caffeine and alcohol exposure. While available evidence supports the notion that IUGR/FGR is related to cognitive impairment and behavioural disorders, the association with ASD or ADHD remains elusive due to the marked variability in the reported outcomes. Few studies have reported a respective higher risk for autism spectrum disorders, yet most of them have failed to identify a statistically significant correlation. Conclusions: While autism spectrum disorders and attention deficiency disorder have been generally associated with FGR children, the existing body of literature offers limited evidence to support this theory.

Endocrine-disrupting chemicals (EDCs) are a diverse group of environmental pollutants capable of interfering with hormonal and immune system regulation. In recent years, increasing concern has been raised about the effects of chemicals, including bisphenols, phthalates, per- and polyfluoroalkyl substances (PFAS), insecticides, and parabens, on maternal and fetal health, primarily due to their widespread exposure in human populations. Pregnancy represents a critical window characterized by tightly regulated hormonal and immunological adaptations. Emerging evidence suggests that EDC exposure during this period may alter maternal microbiota, disrupt immune responses, and interfere with endocrine signaling. These changes may increase susceptibility to bacterial and viral infections, including bacterial vaginosis, urinary tract infections, and intrauterine infections, all of which are associated with adverse pregnancy outcomes. This review summarizes the current evidence on the sources and mechanisms of exposure to endocrine disruptors during pregnancy and examines the potential biological pathways linking endocrine disruption to the development of infections. Particular emphasis is placed on the interactions between immune regulation, hormonal signaling, and changes in the microbiome, which may contribute to increased susceptibility to infections. A deeper understanding of these complex mechanisms is critical to improve risk assessment, develop effective public health strategies, and ultimately protect maternal and fetal health in an environment of increasing chemical exposure. A literature search was conducted using PubMed/MEDLINE, Scopus, and Web of Science, including studies published up to January 2026.

Background/Objectives: Immunohistochemistry is an integral component of the diagnostic approach in breast cancer and remains essential for tumor characterization and therapeutic decision-making. p63 gene expression may have potential diagnostic and prognostic roles in breast cancer patients. Methods: In this study, 127 specimens of invasive breast carcinoma and 50 control cases were evaluated for p63 gene expression and compared to other pathology factors. Results: None of the 50 control cases was assessed as positive for p63 expression. Progesterone and estrogen receptor status were the only factors that demonstrated a statistically significant negative correlation with p63 expression (p = 0.005 and p = 0.017, respectively). Tumor size demonstrated a marginally non-significant correlation with p63 expression (p = 0.051). None of the remaining factors was significantly correlated with p63 expression. Conclusions: In conclusion, p63 expression is inversely correlated with estrogen and progesterone receptor status, and type, size and grade of the tumors are not correlated with the gene’s expression, nor is HER2 status. This conclusion might impact genotype-based stratification pertinent to diagnosis and tailored treatment.

Background/Objectives: Breast metastases originating from extramammary malignant tumors represent an exceptionally rare clinical entity, particularly in the male population. This study aims to review relevant literature on secondary breast involvement in male patients, focusing on clinical presentation, imaging features, histological and immunohistochemical characteristics and management strategies. To date, no published systematic review focusing on this topic exists in the international literature. Methods: A systematic review of the available literature was conducted through a comprehensive search of the PubMed/MEDLINE database up to December 2025. A total of 376 records were identified, of which 98 articles met the inclusion criteria and were included in the analysis. Results: A total of 192 cases were identified, mainly from case reports and small case series. The mean age was 58 years, with similar distribution between breasts and occasional bilateral involvement. Breast metastases often occurred months to years after the primary tumor (mean 32 months) and typically indicated advanced disease with additional metastases. The most common primary tumors were prostate, lung, and melanoma. Diagnosis relied on biopsy with histological and immunohistochemical evaluation. Management was primarily directed at the underlying systemic disease, while surgery, although frequently performed, contributed mainly to diagnostic confirmation and local disease control. Conclusions: Histological identification and immunohistochemical characterization are crucial in the differential diagnosis between primary breast carcinoma and metastatic disease to the breast. The diagnosis of a metastatic lesion, rather than a primary breast malignancy, alters the therapeutic approach.