BDNF Promotes In Vitro Maturation of Sheep Oocytes by Alleviating Oxidative Stress and Endoplasmic Reticulum Stress

In vitro maturation (IVM) is highly susceptible to influences of the culture environment, which can lead to increased intracellular reactive oxygen species (ROS) levels and thereby induce a stress response in oocytes, ultimately reducing the developmental potential of early embryos. Brain-derived neurotrophic factor (BDNF) is an ovarian endocrine factor that can enhance the function of follicular granulosa cells and promote oocyte maturation, but the specific pathways remain unclear. We supplemented IVM cultures of sheep oocytes with BDNF and examined aspects of oocyte nuclear and cytoplasmic maturation. The addition of 50 ng/mL BDNF promoted the expansion of cumulus cells and increased the rates of first polar body extrusion, cleavage, and blastocyst formation. Compared with untreated controls, BDNF-treated oocytes had improved Ca²⁺ homeostasis, enhanced expression of antioxidant genes, decreased ROS levels and expression of endoplasmic reticulum stress genes, and increased mitochondrial membrane potential, mitochondrial biogenesis, and numbers of cells with proper distributions of mitochondria and endoplasmic reticulum. Further analysis indicated that BDNF affected oocyte maturation by increasing the numbers of transzonal projections and gap junctions during the IVM process. In summary, the addition of BDNF during the IVM process improved sheep oocyte maturation and embryo development by reducing oxidative stress and endoplasmic reticulum stress. These findings deepen our understanding of the regulatory mechanisms of BDNF during IVM and provide experimental data to improve in vitro embryo production from sheep oocytes.