Success in assisted reproductive techniques (ART) is influenced by gamete and embryo quality but the assessment of these parameters has been thwarted by the lack of reliable biomarkers. Follicular fluid and cumulus oophorus cells may provide biomarkers due to their close relationship to the oocyte. These cells produce antioxidants and thus protect the oocyte from oxidative damage exerted by reactive oxygen species (ROS). ROS and antioxidants are known to intervene in reproductive physiology and pathology, but their roles are unclear. It is hypothesized that superoxide dismutase (SOD), a first line antioxidant enzyme, is associated with oocyte quality. Cells obtained in the course of ART for the treatment of infertility due to male factor or female pathology were processed for SOD intracellular isoforms (CuZnSOD and MnSOD) immunodetection, total SOD activity and isoforms content. Cells presented strong positive staining for CuZnSOD and MnSOD. SOD activity decreased with increasing female age but was increased in endometriosis and in ovulatory dysfunction. When male factor was the cause for infertility, successful ART was associated with higher SOD activity. Variations in SOD emphasize the relevance of oxidative stress in the oocyte maturation process. These variations also suggest that SOD is a potential biomarker for ART success.

The aging process is characterized by progressive accumulation of damaged biomolecules in the endoplasmic reticulum, as result of increased oxidative stress accompanying cellular senescence. In agreement, we hypothesized that WI-38 human cellular models of replicative senescence and stress-induced premature senescence (SIPS) induced by hydrogen peroxide (H₂O₂-SIPS) or copper sulfate (CuSO₄-SIPS) would present endoplasmic reticulum chaperoning mechanisms impairment and unfolded protein response activation. Results show that in replicative senescence and CuSO₄-SIPS, immunoglobulin binding protein, calnexin, protein disulfide isomerase, and ER oxireductin-1 levels adjust to restore proteostasis and inositol-requiring enzyme-1 (IRE1)-, activating transcription factor 6 (ATF6)-, and pancreatic ER kinase (PERK)-mediated unfolded protein response are activated. However, H₂O₂-SIPS does not exhibit IRE1 and ATF6 pathways activation but a PERK-mediated upregulation of CCAAT/enhancer-binding protein homologous protein, showing that CuSO₄-SIPS mimics better the endoplasmic reticulum molecular events of replicative senescence than H₂O₂-SIPS. Moreover, unfolded protein response activation is required for both SIPS models induction, because PERK and IRE1 inhibitors decreased senescence-associated beta-galactosidase appearance. In CuSO₄-SIPS, the decrease in senescence levels is associated with PERK-driven, but IRE1 independent, cell cycle arrest while in H₂O₂-SIPS cell proliferation is PERK independent. These results add a step further on the molecular mechanisms that regulate senescence induction; moreover, they validate CuSO₄-SIPS model as a useful tool to study cellular stress responses during aging, hoping to postpone age-related health decline.

As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF). In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu. An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction. In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.

For a successful pregnancy to occur, a predecidualized receptive endometrium must be invaded by placental differentiated cells (extravillous trophoblast cells (EVTs)) and, at the same time, continue decidualization. EVT invasion is aimed at anchoring the placenta to the maternal uterus and ensuring local blood supply increase necessary to provide normal placental and foetal development. The first is achieved by migrating through the maternal endometrium and deeper into the myometrium, while the second by transforming uterine spiral arteries into large vessels. This process is a tightly regulated battle comprising interests of both the mother and the foetus. Invading EVTs are required to perform a scope of functions: move, adhere, proliferate, differentiate, interact, and digest the extracellular matrix (ECM); tolerate hypoxia; transform the maternal spiral arteries; and die by apoptosis. All these functions are modulated by their surrounding microenvironment: oxygen, soluble factors (e.g., cytokines, growth factors, and hormones), ECM proteins, and reactive oxygen species. A deeper comprehension of oxidative uterine microenvironment contribution to trophoblast function will be addressed in this review.