The tumor microenvironment (TME) in ovarian cancer (OC) has much greater complexity than previously understood. In response to aggressive pro-angiogenic stimulus, blood vessels form rapidly and are dysfunctional, resulting in poor perfusion, tissue hypoxia, and leakiness, which leads to increased interstitial fluid pressure (IFP). Decreased perfusion and high IFP significantly inhibit the uptake of therapies into the tumor. Within the TME, there are numerous inhibitor cells, such as myeloid-derived suppressor cells (MDSCs), tumor association macrophages (TAMs), regulatory T cells (Tregs), and cancer-associated fibroblasts (CAFs) that secrete high numbers of immunosuppressive cytokines. This immunosuppressive environment is thought to contribute to the lack of success of immunotherapies such as immune checkpoint inhibitor (ICI) treatment. This review discusses the components of the TME in OC, how these characteristics impede therapeutic efficacy, and some strategies to alleviate this inhibition.

There has been emerging research linking per- and poly-fluoroalkyl substances (PFAS) to gamete viability and fertility. PFAS, prevalent in the environment and water supplies, undergo slow degradation due to their C-F bond and a long half-life (2.3–8.5 years). In females, PFAS inhibit the hypothalamic–pituitary–gonadal (HPG) axis, reducing follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, leading to the inhibition of androgen and estradiol production. PFAS have been found to cause detrimental effects on egg quality through impairing folliculogenesis. In males, PFAS can impair sperm motility and morphology: two fundamental qualities of successful fertilization. PFAS exposure has been proven to inhibit testosterone production, sperm capacitation, and acrosomal reaction. After fertilization, the results of PFAS exposure to embryos have also been investigated, showing reduced development to the blastocyst stage. The aim of this review is to report the main findings in the literature on the impact of PFAS exposure to gamete competency and fertilization capability by highlighting key studies on both male and female fertility. We report that there is significant evidence demonstrating the negative impacts on fertility after PFAS exposure. At high doses, these environmentally abundant and widespread compounds can significantly affect human fertility.

The expansion of the Alberta Oil Sands Region (AOSR) has increased the deposition of petroleum-derived chemicals into the surrounding environment. Among these, polycyclic aromatic compounds (PACs), including sulfur-containing heterocyclic hydrocarbons, have been detected in exposed local wildlife, yet the reproductive toxicity and genotoxicity of this suite of PACs remain largely unexplored. This study examined the effects of dibenzothiophene (DBT) and its alkylated congener, 2,4,7-trimethyldibenzothiophene (2,4,7-DBT), on estradiol (E2) synthesis and metabolism in granulosa cells (SIGCs). Cells were exposed to DBT or 2,4,7-DBT for 24 h at concentrations detected in AOSR wildlife tissues (0, 0.1, 1 and 10 nM). We measured the gene expression of markers involved in E2 synthesis, signaling and metabolism, E2 output via ELISA and E2 metabolite production via HPLC-MS/MS. Exposure to 2,4,7-DBT, but not DBT, shifted E2 metabolism towards 4-OHE2, a genotoxic E2 metabolite. DNA damage was assessed by γH2Ax expression, alongside DNA repair (Parp1) and survival markers (pAKT). Interestingly, both DBT and 2,4,7-DBT increased DNA damage and triggered apoptosis via a caspase-independent mechanism. Given the critical role of granulosa cells in steroidogenesis and fertility, these findings highlight the endocrine-disruptive effects of sulfur-containing heterocyclic PACs and their potential to compromise reproductive health in exposed mammals.