Diseases are complex systems that can be studied through the integration of data derived from different disciplines to obtain a global and reliable picture of the biological phenomenon under investigation. Based on the recent observations that the metabolomics profiling of follicular fluids reflects the ovarian microenvironment of women and that endometriosis represents an example of complex diseases, clearly diagnosed by laparoscopy, we thought that the follicular fluids of endometriosis patients can represent a study model to evaluate the possibility of integrating data obtained by different approaches. Hence, the aim of this work was to analyze and integrate different clinical chemistry parameters with specific reference to the metabolic profile, inflammatory state and cell damage by a ¹H-NMR approach and biochemical analysis in the follicular fluids of women with different stages of endometriosis (I–II and III–IV) subjected to the In Vitro Fertilization (IVF) cycle. Our analysis evidenced that in the follicular fluids of endometriosis patients the levels of phospholipids, lactate, insulin, PTX3, CXCL8, CXCL10, CCL11 and VEGF were higher whereas those of some fatty acids, lysine, choline, glucose, aspartate, alanine, leucine, valine, proline, phosphocholine, total LDH as well its LDH-3 isoform were lower in comparison to the control group. The levels of LDHB, PTX3 and insulin receptor were also confirmed by RT-PCR applied on cumulus cells surrounding oocytes retrieved from the patients. The reduced oocyte quality observed in patients with endometriosis can be certainly correlated to the different levels of these molecules. These data represent how the integration of different experimental approaches may be useful for understanding the underlying mechanisms of a complex disease and can lead to a better clinical management of endometriosis.

The environmental release of titanium dioxide nanoparticles (TiO₂NPs) associated with their intensive use has been reported to have a genotoxic effect on male fertility. TiO₂NP is able to bind and transport environmental pollutants, such as cadmium (Cd), modifying their availability and/or toxicity. The aim of this work is to assess the in vitro effect of TiO₂NPs and cadmium interaction in human sperm cells. Semen parameters, apoptotic cells, sperm DNA fragmentation, genomic stability and oxidative stress were investigated after sperm incubation in cadmium alone and in combination with TiO₂NPs at different times (15, 30, 45 and 90 min). Our results showed that cadmium reduced sperm DNA integrity, and increased sperm DNA fragmentation and oxidative stress. The genotoxicity induced by TiO₂NPs-cadmium co-exposure was lower compared to single cadmium exposure, suggesting an interaction of the substances to modulate their reactivity. The Quantitative Structure-Activity Relationship (QSAR) computational method showed that the interaction between TiO₂NPs and cadmium leads to the formation of a sandwich-like structure, with cadmium in the middle, which results in the inhibition of its genotoxicity by TiO₂NPs in human sperm cells.

Agarwal A, et al. World J Mens Health. 2022 Oct;40(4):636-652. https://doi.org/10.5534/wjmh.210202

Titanium dioxide nanoparticles (NPs-TiO₂ or TiO₂-NPs) have been employed in many commercial products such as medicines, foods and cosmetics. TiO₂-NPs are able to carry antibiotics to target cells enhancing the antimicrobial efficiency; so that these nanoparticles are generally used in antibiotic capsules, like lincomycin, added as a dye. Lincomycin is usually used to treat pregnancy bacterial vaginosis and its combination with TiO₂-NPs arises questions on the potential effects on fetus health. This study investigated the potential impact of TiO₂-NPs and lincomycin co-exposure on human amniocytes in vitro. Cytotoxicity was evaluated with trypan blue vitality test, while genotoxic damage was performed by Comet Test, Diffusion Assay and RAPD-PCR for 48 and 72 exposure hours. Lincomycin exposure produced no genotoxic effects on amniotic cells, instead, the TiO₂-NPs exposure induced genotoxicity. TiO₂-NPs and lincomycin co-exposure caused significant increase of DNA fragmentation, apoptosis and DNA damage in amniocytes starting from 48 exposure hours. These results contribute to monitor the use of TiO₂-NPs combined with drugs in medical application. The potential impact of antibiotics with TiO₂-NPs during pregnancy could be associated with adverse effects on embryo DNA. The use of nanomaterials in drugs formulation should be strictly controlled in order to minimize risks.

Reproductive tract infections account for approximately 15% of male infertility cases. Escherichia coli (E. coli) represents the most frequently isolated bacterial strain in the semen of infertile men. All Gram-negative bacteria constitutively produce outer membrane vesicles (OMVs). The present study proved, for the first time, the involvement of OMVs in human sperm function. E. coli OMVs were isolated by ultracentrifugation and characterized via sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis. Human sperm was exposed to OMVs (8 µg/mL) for different times (30, 45, 60 and 90 min). The vitality, motility, morphology, ROS level and DNA fragmentation of spermatozoa were evaluated. OMVs reduced the progressive motility and increased the immobile spermatozoa amount after 30 min of treatment. In addition, a significant increase in the percentage of intracellular ROS and sperm DNA fragmentation was recorded for each vesicular exposure time. These preliminary findings prove that OMVs contribute to altering human sperm function via two mechanisms: (i) impaired motility and (ii) DNA fragmentation.