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Nowadays, developing countries have seen a reduction in male reproductive parameters, and it has been linked to the exposure of endocrine disrupting chemicals (EDCs), which are able to mimic or disrupt steroid hormone actions. Also, nanoparticles have shown effects on the male reproductive system, in particular the use of TiO2-NPs in drugs, cosmetics, and food as pigment additives, and, thanks to their small size (1–100 nm), provide themselves the opportunity to be internalized by the body and pass the blood–testis barrier (BTB). Therefore, TiO2-NPs can act on spermatogenesis and spermatozoa. In this study, we carried out an in vitro assay on human spermatozoa to evaluate the effects of TiO2-NPs at the concentrations of 500, 250, 100, and 50 ppm. Exposure did not statistically alter sperm parameters (e.g., motility and viability) but induced damage to sperm DNA and the expression of biomarkers by spermatozoa. This immunofluorescence investigation showed a positivity for biomarkers of stress (HSP70 and MTs) on the connecting piece of spermatozoa and also for sex hormone binding globulin (SHBG) biomarkers. The SHBG protein acts as a carrier of androgens and estrogens, regulating their bioavailability; therefore, its expression in the in vitro assay did not rule out the ability of TiO2-NPs to act as endocrine disruptors. [ABSTRACT FROM AUTHOR]

Simple Summary: The question of emerging pollutants, among which nanoplastics occupy a predominant position, requires further investigation regarding their interaction with different biological systems, including reproductive cells. In the present evaluation, deleterious effects on sperm cells have been correlated with polystyrene nanoparticle size. Indeed, the decline of fundamental parameters such as motility, acrosome and DNA integrity, and ROS physiological production, has been associated with the action of nanoparticles with a diameter of 50 nm, compared to particles with larger size (100 nm). In addition, the expression of protective biomarkers, such as HSP70s, has been shown to contribute to damage recovery. The results warn about persistent and chronic contamination of plastics with a focus on infertility to elucidate the metabolic and biochemical changes of sperm cells in the presence of stressful xenobiotics. The ubiquitous spread of Polystyrene nanoplastics (PS-NPs) has rendered chronic human exposure an unavoidable phenomenon. The biodistribution of such particles leads to bioaccumulation in target organs including the testis, the site of sperm maturation. The purpose of this research has been to estimate the impact of PS-NPs (50 and 100 nm) on the metabolism of mature spermatozoa. The analysis of the semen parameters has revealed a higher toxicity of the smaller sized PS-NPs, which have negatively affected major organelles, leading to increased acrosomal damage, oxidative stress with the production of ROS, DNA fragmentation, and decreased mitochondrial activity. PS-NPs of 100 nm, on the other hand, have mainly affected the acrosome and induced a general state of stress. An attempt has also been made to highlight possible protective mechanisms such as the expression of HSP70s and their correlation among various parameters. The results have evinced a marked production of HSP70s in the samples exposed to the smaller PS-NPs, negatively correlated with the worsening in oxidative stress, DNA fragmentation, and mitochondrial anomalies. In conclusion, our results have confirmed the toxicity of PS-NPs on human spermatozoa but have also demonstrated the presence of mechanisms capable of counteracting at least in part these injuries. [ABSTRACT FROM AUTHOR]

Administration of 1000–1500 mg/day D-Chiro-Inositol (DCIns) or a combination of Myo-Inositol (MyoIns) and DCIns in their plasma molar ratio (40:1) for three or more months are among recommended treatments for metabolic syndrome and/or Polycystic Ovary Syndrome (PCOS). We previously confirmed the efficacy of this formulation (8.2 mg/day MyoIns and 0.2 mg/day DCIns for 10 days) in a mouse PCOS model, but also observed negative effects on ovarian histology and function of formulations containing 0.4–1.6 mg/day DCIns. We therefore analyzed effects of higher doses of DCIns, 5, 10 and 20 mg/day, administered to young adult female mice for 21 days, on ovarian histology, serum testosterone levels and expression of the ovarian enzyme aromatase. Five mg/day DCIns (human correspondence: 1200 mg/day) altered ovarian histology, increased serum testosterone levels and reduced the amount of aromatase of negative controls, suggesting the induction of an androgenic PCOS model. In contrast, 10–20 mg/day DCIns (human correspondence: 2400–4800 mg/day) produced ovarian lesions resembling those typical of aged mice, and reduced serum testosterone levels without affecting aromatase amounts, suggesting a failure in steroidogenic gonadal activity. Notwithstanding physiological/biochemical differences between mice and humans, the observed pictures of toxicity for ovarian histology and function recommend caution when administering DCIns to PCOS patients at high doses and/or for periods spanning several ovulatory cycles. [ABSTRACT FROM AUTHOR]

Among the extensive public and scientific interest in the use of phytochemicals to prevent or treat human diseases in recent years, natural compounds have been highly investigated to elucidate their therapeutic effect on chronic human diseases including cancer, cardiovascular disease, and neurodegenerative disease. Curcumin, an active principle of the perennial herb Curcuma longa, has attracted an increasing research interest over the last half-century due to its diversity of molecular targets, including transcription factors, enzymes, protein kinases, growth factors, inflammatory cytokines, receptors, and it's interesting pharmacological activities. Despite that, the clinical effectiveness of the native curcumin is weak, owing to its low bioavailability and rapid metabolism. Preclinical data obtained from animal models and phase I clinical studies done in human volunteers confirmed a small amount of intestinal absorption, hepatic first pass effect, and some degree of intestinal metabolism, might explain its poor systemic availability when it is given via the oral route. During the last decade, researchers have attempted with new pharmaceutical methods such as nanoparticles, liposomes, micelles, solid dispersions, emulsions, and microspheres to improve the bioavailability of curcumin. As a result, a significant number of bioavailable curcumin-based formulations were introduced with a varying range of enhanced bioavailability. This manuscript critically reviews the available scientific evidence on the basic and clinical effects and molecular targets of curcumin. We also discuss its pharmacokinetic and problems for marketing curcumin as a drug. [ABSTRACT FROM AUTHOR]