BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility

Abstract

Benzo[a]pyrene (BaP) is a ubiquitous environmental pollutant and carcinogen that is frequently found in particulate matter, with a diameter of ≤2.5 μm (PM2.5). It has been reported to interrupt the normal reproductive system, but the exact molecular basis has not been clearly defined. To understand the underlying mechanisms regarding how BaP exposure disrupts female fertility, we evaluated oocyte quality by assessing the critical regulators and events during oocyte meiotic maturation and fertilization. We found that BaP exposure compromised the mouse oocyte meiotic progression by disrupting normal spindle assembly, chromosome alignment, and kinetochore-microtubule attachment, consequently leading to the generation of aneuploid eggs. In addition, BaP administration significantly decreased the fertilization rate of mouse eggs by reducing the number of sperm binding to the zona pellucida, which was consistent with the premature cleavage of N terminus of zona pellucida sperm-binding protein 2 and precocious exocytosis of ovastacin. Furthermore, BaP exposure interfered with the gamete fusion process by perturbing the localization and protein level of Juno. Notably, we found that BaP exposure induced oxidative stress with an increased level of reactive oxygen species and apoptosis in oocytes and thereby led to the deterioration of critical regulators and events during oocyte meiotic progression and fertilization. Our data document that BaP exposure reduces female fertility impairing oocyte maturation and fertilization ability induced by oxidative stress and early apoptosis in murine models.-Zhang, M., Miao, Y., Chen, Q., Cai, M., Dong, W., Dai, X., Lu, Y., Zhou, C., Cui, Z., Xiong, B. BaP exposure causes oocyte meiotic arrest and fertilization failure to weaken female fertility.

Benzo[b]fluoranthene Impairs Mouse Oocyte Maturation via Inducing the Apoptosis

“…Although oocyte maturation progression was not affected by BbF, its toxicity may decrease the embryonic development potential. Previous studies also found that other individual component of PAH was toxic to oocytes; Bap and B[ghi]P exposure caused nuclear and cytoplasmic maturation failure, via impairing the meiotic apparatus ( Miao et al, 2018 ; Zhang et al, 2018 ; Li et al, 2019 ). These studies demonstrated that PAHs showed a similar effect on oocyte maturation.…”

Tributyltin oxide exposure impairs mouse oocyte maturation and its possible mechanisms

“…Several studies indicate that aberrant spindle assemble and chromosome misalignment participate in impairing the female reproduction ability in various species . Also, disrupted spindle assembly and misaligned chromosomes are supposed to be related to producing aneuploidy oocytes, which are important during infertility . Aneuploidy is a contributor to poor quality of gamete, which will also produce a zygote with poor quality.…”

“…The sperm were capacitated in an atmosphere of 5% CO 2 and saturated humidity at 37°C for 1 hour and added to the oocytes at an approximate concentration of 1 to 2.5 × 10 6 /mL sperm for 4 to 6 hours. The presence of two pronuclei was regarded as successful fertilization . Four replicates were performed and about 200 oocytes in total were observed for each group.…”

“…Studies revealed that ROS level was regarded as an important event during oocytes development and might contribute to accelerating apoptosis in oocytes. 26,28 So we next detected the intracellular ROS generation and earlystage apoptosis, to further investigate the underlying mechanism of TBTO's toxicity on mouse oocytes meiotic maturation. As reflected by Figure 3A, TBTO treatment increased the ROS fluorescence signal intensity in a dosedependent manner.…”

Perfect date—the review of current research into molecular bases of mammalian fertilization

“…Yet, fluorescent live imaging of good-quality oocytes is needed to characterize Juno dynamics prior to fertilization and explain the discrepancy between the localization patterns immunodetected in fixed and live human samples reported in this study. Of note, two recent studies reported that the exposure of the female mice to widespread environmental pollutants, melamine and benzo[a]pyrene, altered expression and localization of Juno and adversely effected mouse egg fertilizing capacity assessed in vitro [82,83]. Future studies should address whether the similar risk of reproductive toxicity exists in humans.…”