Cyclophosphamide (CY) is a chemotherapeutic drug that is commonly used to treat malignancies of the ovary, breast, and hematology, as well as autoimmune disorders. As a cofactor of mitochondrial multienzyme complexes, alpha lipoic acid (ALA) is well known for its antioxidant characteristics, which operate directly on the scavenging of reactive oxygen species (ROS) and indirectly on the intracellular recycling of other antioxidants. However, the underlying mechanisms through which CY exerts its toxic effects on meiosis and oocyte quality, as well as a viable approach for protecting oocyte quality and preserving fertility, remain unknown. In present study, immunostaining and fluorescence intensity quantification were applied to assess the effects of CY and ALA supplementation on the key processes during the oocyte meiotic maturation. Our results show that supplementing oocytes with ALA, a well-known antioxidant and free radical scavenger, can reverse CY-induced oocyte meiotic maturation failure. Specifically, we found that CY exposure caused oocyte meiotic failure by disrupting meiotic organelle dynamics and arrangement, as well as a prominently impaired cytoskeleton assembly. In addition, CY caused an abnormal distribution of mitochondrion and cortical granules, two indicators of oocyte cytoplasmic maturation. More importantly, we show that ALA supplementation effectively reverses CY-induced meiotic failure and oocyte quality decline by suppressing oxidative stress-induced DNA damage and apoptosis in oocytes. Collectively, our data reveal that ALA supplementation is a feasible approach to protect oocytes from CY-exposed deterioration, providing a better understanding of the mechanisms involved in chemotherapy-induced meiotic failure.

Butylparaben is an ubiquitous environmental endocrine disruptor, that is commonly used in cosmetics and personal care product due to its anti-microbial properties. Butylparaben has been shown to cause developmental toxicity, endocrine and metabolic disorders and immune diseases. However, little is known about the impact on female fertility, especially oocyte quality. In the present study, we reported that butylparaben influenced female fertility by showing the disturbed oocyte meiotic capacity and fertilization potential. Specifically, butylparaben results in the oocyte maturation arrest by impairing spindle/chromosome structure and microtubule stability. Besides, butylparaben results in fertilization failure by impairing the dynamics of Juno and ovastacin and the sperm binding ability. Last, single-cell transcriptome analysis showed that butylparaben-induced oocyte deterioration was caused by mitochondrial dysfunction, which led to the accumulation of ROS and occurrence of apoptosis. Collectively, our study indicates that mitochondrial dysfunction and redox perturbation is the major cause of the weakened female fertility expoesd to butylparaben.

Kif16A, a member of the kinesin‐3 family of motor proteins, has been shown to play crucial roles in inducing mitotic arrest, apoptosis, and mitotic cell death. However, its roles during oocyte meiotic maturation have not been fully defined. In this study, we report that Kif16A exhibits unique accumulation on the spindle apparatus and colocalizes with microtubule fibers during mouse oocyte meiotic maturation. Targeted depletion of Kif16A using gene‐targeting siRNA disrupts the progression of the meiotic cell cycle. Furthermore, Kif16A depletion leads to aberrant spindle assembly and chromosome misalignment in oocytes. Our findings also indicate that Kif16A depletion reduces tubulin acetylation levels and compromises microtubule resistance to depolymerizing drugs, suggesting its crucial role in microtubule stability maintenance. Notably, we find that the depletion of Kif16A results in a notably elevated incidence of defective kinetochore‐microtubule attachments and the absence of BubR1 localization at kinetochores, suggesting a critical role for Kif16A in the activation of the spindle assembly checkpoint (SAC) activity. Additionally, we observe that Kif16A is indispensable for proper actin filament distribution, thereby impacting spindle migration. In summary, our findings demonstrate that Kif16A plays a pivotal role in regulating microtubule and actin dynamics crucial for ensuring both spindle assembly and migration during mouse oocyte meiotic maturation.

Purpose Nano graphene oxide (nGO), as a type of engineered carbon nanomaterial, has witnessed significant growth in biomedical applications. Given the likelihood of accumulation of these materials in human tissues or organs, it becomes imperative to comprehensively assess the toxicological profile of nGO, particularly concerning female reproductive health. Methods Germinal vesicle (GV) porcine oocytes were cultured at 38.5 °C to the specific developmental stage for subsequent analysis. The nGO was diluted with the maturation medium to the final concentrations of 10, 50, 100 and 200 μg/ml, respectively. Immunostaining and fluorescence intensity quantification were applied to assess the effects of nGO exposure on the key processes during the oocyte meiotic maturation. Results We observed that exposure to nGO led to compromised meiotic competency in porcine oocytes during in vitro culture. Specifically, nGO exposure resulted in reduced acetylation levels of α-tubulin and misattachment of kinetochore-microtubules, thereby disrupting spindle/chromosome organization and impeding meiotic progression. Furthermore, nGO exposure perturbed actin dynamics, potentially hindering spindle migration and cortical polarization during oocyte meiosis. Additionally, mislocalization and premature exocytosis of ovastacin were observed following nGO exposure. Notably, nGO exposure induced mitochondrial dysfunction, DNA damage, and oxidative stress, ultimately triggering apoptosis and impeding the maturation of porcine oocytes and the development of post-fertilized embryos. Conclusion Our findings underscore the potential deleterious effects of nGO on mammalian oocyte quality, while also contributing valuable insights into the impact of environmental nanoparticle release on female germ cell development. Graphical Abstract