Understanding the cascade heterojunction of CuPc/Bi-MOF for photoelectrochemical nitrate reduction.

Herein, a CuPc/Bi-MOF cascade heterojunction is synthesized exhibiting an excellent NH3 yield (7.13 µg h-1 cm-2) and stability. Characterization studies show that the cascade heterostructure with a unique morphology and oxygen vacancies offers new insights into future photoelectrocatalytic material design.

Oral isoniazid causes oxidative stress, oocyte deterioration and infertility in mice.

Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.

Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice.

Lead, a common metallic contaminant, is widespread in the living environment, and has deleterious effects on the reproductive systems of humans and animals. Although numerous toxic effects of lead have been reported, the effects and underlying mechanisms of the impacts of lead exposure on the female reproductive system, especially oocyte maturation and fertility, remain unknown. In this study, mice were treated by gavage for seven days to evaluate the reproductive damage and role of Nrf2-mediated defense responses during lead exposure. Lead exposure significantly reduced the maturation and fertilization of oocytes in vivo. Additionally, lead exposure triggered oxidative stress with a decreased glutathione level, increased amount of reactive oxygen species, and abnormal mitochondrial distribution. Moreover, lead exposure caused histopathological and ultrastructural changes in oocytes and ovaries, along with decreases in the activities of catalase, glutathione peroxidase, total superoxide dismutase, and glutathione-S transferase, and increases in the levels of malonaldehyde in mouse ovaries. Further experiments demonstrated that lead exposure activated the Nrf2 signaling pathway to protect oocytes against oxidative stress by enhancing the transcription levels of antioxidant enzymes. In conclusion, our study demonstrates that lead activates the Nrf2/Keap1 pathway and impairs oocyte maturation and fertilization by inducing oxidative stress, leading to a decrease in the fertility of female mice.

Ochratoxin A exposure causes meiotic failure and oocyte deterioration in mice.

Ochratoxin A (OTA) is a mycotoxin produced by fungi and occurs naturally in various foodstuffs and some animal-derived products. This mycotoxin can cause deleterious effects on kidney, liver, central nervous, and immune system. However, potential mechanisms regarding how OTA disrupts the mammalian oocyte quality have not been clearly defined. In this study, we proved that OTA weakened oocyte quality by impairing oocyte meiotic maturation. We found that female mice treated with 1 mg/kg body weight OTA by intraperitoneal (IP) injection for 7 days displayed ovarian dysfunction and decreased offspring number. We also found that OTA treatment at 7.5 µM for 16 h decreased the rate of first polar body extrusion by disrupting spindle and chromosome alignment. In addition, OTA caused oxidative stress by inducing the accumulation of reactive oxygen species and consumption of antioxidants during meiosis, consequently resulting in oocytes apoptosis. Mitochondrial damage and insufficient energy supply were also observed in OTA-pretreated oocytes, which led to the meiotic failure of oocyte. Moreover, the epigenetic modifications were also affected, showing with altered 5 mC, 5hmC, H3K9ac, and H3K9me3 levels in mice oocytes. In summary, these results showed that OTA could decrease oocyte maturation and fertility by inducing oxidative stress and epigenetic changes.

Reproductive toxicity of acute Cd exposure in mouse: Resulting in oocyte defects and decreased female fertility.

Cadmium (Cd), a known metal contaminant, is widespreadly used in industry, thereby human health is severely affected through the way of occupational and environmental exposure. The adverse effects of the exposure to Cd on the female reproductive system, especially oocyte maturation and fertility have not been clearly defined. In this study, we found the arrested development of ovaries and uteri after Cd exposure and determined oocyte quality via assessing the key regulators during meiotic maturation and fertilization. We found that Cd exposure impeded the mouse oocyte meiotic progression by disrupting the normal spindle assembly, chromosome alignment and actin cap formation. Besides, exposure to Cd induced oxidative stress with the increased reactive oxygen species and apoptosis levels, leading to abnormal mitochondrial distribution, insufficient energy supply, and DNA damage, which ultimately led to oocyte quality deterioration. We also analyzed the effects of cadmium on epigenetic modifications, and the levels of 5mC, H3K9me3 and H3K9ac decreased after acute exposure to cadmium. Further experiments showed that the litter size in Cd-exposed female mice reduced, thereby indicating increased reproductive Cd toxicity. In conclusion, Cd exposure impairs oocyte maturation and fertilization ability induced by oxidative stress, early apoptosis and epigenetic modifications, which lead to the decrease of female fertility.