Dibutyl phthalate (DBP), one of the most widely used plasticizers, is a known environmental endocrine disruptor that impairs male and female fertility. In this study, oral administration of DBP was given to pregnant mice on 14.5 days post coitus (dpc) for 3 days; and additionally, DBP was added into the culture of 14.5 dpc fetal ovaries for 3 days. DBP exposure during gestation disturbed the progression of meiotic prophase I of mouse oocytes, specifically from the zygotene to pachytene stages. Meanwhile, the DBP-exposed pachytene oocytes showed increased homologous recombination sites and unrepaired DNA damage. Furthermore, DBP caused DNA damage by increasing oxidative stress, decreased the expression of multiple critical meiotic regulators, and consequently induced oocyte apoptosis. Moreover, the effect of DBP on meiosis I prophase involved estrogen receptors α and β. Collectively, these results demonstrated a set of meiotic defects in DBP-exposed fetal oocytes. As aberrations in homologous recombination can result in aneuploid gametes and embryos, this study provides new support for the deleterious effects of phthalates.

HT-2 toxin (HT-2), a mycotoxin produced by Fusarium species, is detected in a variety of cereal grain-based human food and animal feed. Apart from its well-established immunotoxicity and haematotoxicity, it also causes reproductive disorders. In the present study, we revealed the adverse effects of HT-2 on early oogenesis at the foetal stage. Pregnant mice were orally administered with HT-2 for 3 days at mid-gestation. Oocytes from female foetuses exposed to HT-2 displayed defects in meiotic prophase, including unrepaired DNA damage, elevated recombination levels, and reduced expression of meiotic-related genes. Subsequently, increased oxidative stress was observed in the foetal ovaries exposed to HT-2, along with the elevated levels of reactive oxygen species, malondialdehyde, catalase, and superoxide dismutase 1/2, thereby resulting in impaired mitochondrial membrane potential and cell apoptosis. Furthermore, pre-treatment with urolithin A, a natural compound with antioxidant activities, partially reversed the delayed meiotic process by alleviating oxidative stress. Since early oogenesis is essential to determine female fertility in adult life, this study indicated that brief maternal exposure to HT-2 toxin may compromise the fertility of a developing female foetus.

Diesel engine exhaust (DEE) is a complex mixture of toxic gases, halogenated aromatic hydrocarbons, alkyl polycyclic aromatic hydrocarbons, polycyclic aromatic hydrocarbons, benzene derivatives, metals and diesel exhaust particles (DEPs) generated from the incomplete combustion of diesel fuel. Many of the compounds in this mixture can cause oxidative damage to DNA and are considered carcinogenic for humans. Further, chronic DEE exposure increases risks of cardiovascular and pulmonary diseases. Despite these pervasive health risks, there is limited and inconsistent information regarding genetic factors conferring susceptibility or resistance to DEE genotoxicity. The present study evaluated the effects of polymorphisms in two base excision repair (BER) genes (OGG1 Ser326Cys and XRCC1 Arg280His), one homologous recombination (HRR) gene (XRCC3 Thr241Met) and two xenobiotic metabolism genes (GSTM1 and GSTT1) on the genotoxicity profiles among 123 mechanics exposed to workplace DEE. Polymorphisms were determined by PCR-RFLP. In comet assay, individuals with the GSTT1 null genotype demonstrated significantly greater % tail DNA in lymphocytes than those with non-null genotype. In contrast, these null individuals exhibited significantly lower frequencies of binucleated (BN) cells and nuclear buds (NBUDs) in buccal cells than non-null individuals. Heterozygous hOGG1 326 individuals (hOGG1 326 Ser/Cys) exhibited higher buccal cell NBUD frequency than hOGG1 326 Ser/Ser individuals. Individuals carrying the XRCC3 241 Met/Met polymorphism also showed significantly higher buccal cell NBUD frequencies than those carrying the XRCC3 241 Thr/Thr polymorphism. We found a high flow of particulate matter with a diameter of < 2.5 μm (PM₂.₅) in the workplace. The most abundant metals in DEPs were iron, copper, silicon and manganese as detected by transmission electron microscopy–energy-dispersive X-ray spectroscopy (TEM-EDX). Scanning electron microscopy (SEM-EDS) revealed particles with diameters smaller than PM₂.₅, including nanoparticles forming aggregates and agglomerates. Our results demonstrate the genotoxic effects of DEE and the critical influence of genetic susceptibility conferred by DNA repair and metabolic gene polymorphisms that shed light into the understanding of underlying mechanisms.