Crotonaldehyde Exposure Decreases Ovarian Quality And Impairs Oocyte Development In Mice

In recent years,reproductive health issues have become a growing concern around the world,and environmental pollution is a key factor in causing reproductive health problems.In environmental pollution,aldehydes have a non-negligible role.Crotonaldehyde,or 2-crotonaldehyde(CR),is anα,β-unsaturated aldehyde with a wide distribution in chemical products and various fumes and exhaust gases.Notably,CR can also be synthesized in vivo through lipid metabolism and is both an initiator and an end product of lipid peroxidation.Current studies have found that CR exerts toxic effects in several human systems;however,it is not clear whether CR exposure has effects on female reproduction.In the present study,we developed a 28-day gavage administration mouse toxicology model.We found that CR exposure affected growth and decreased ovarian weight and ovarian coefficient in mice.We next performed metabolomic analysis of ovaries,and we screened four signaling pathways including steroid biosynthesis,nicotinate and nicotinamide metabolism,oxidative phosphorylation,and adenosine monophosphate-activated protein kinase,from which four differential metabolites including corticosterone,estriol,nicotinamide,and NAD~+were screened as biomarkers.Based on the obtained differential metabolic pathways,we conducted a targeted study on mouse ovaries.We found that CR affected follicular development,and further studies revealed that it interferes with follicular development by affecting the growth differentiation factor 9/bone morphogenetic protein 15(GDF9/BMP15)pathway.In addition,we found that CR triggered ovarian inflammation through the interleukin 1β/tumor necrosis factorα(IL-1β/TNF-α)pathway triggered ovarian inflammation.We attempted to explain the inflammation from a mitochondrial perspective and found that CR caused imbalance in mitochondrial fusion division,decreased the expression of related electron transport chain complexes,and caused mitochondrial autophagy.At the oocyte level,CR caused a decrease in the rate of oocyte first polar body expulsion and interferes with the meiotic progression of oocytes,suggesting that the developmental potential of oocytes is negatively affected.Subsequently,we found that CR increased the level of reactive oxygen species in oocytes and induced the onset of early apoptosis.Taken together,our results suggest that crotonaldehyde exposure leads to decreased ovarian quality and causes impaired oocyte development.