Figure 1.

The effects of the high levels of NEFA in ovarian cells. Some pathological nutrition statuses including negative energy balance or obesity or high-fat diet and in vitro exposure cause elevated NEFA levels in serum and follicular fluid. Impaired energy metabolism, ER stress, mitochondrial dysfunction, increased lipid content, increased ROS production, and increased oxidative stress are the common consequences of high levels of NEFA on ovarian cells (including granulosa cells, cumulus cells, and theca cells), oocytes, and blastocysts. Besides, there are some specific consequences in different cell types. The cell survival, proliferation, and steroidogenesis of granulosa cells and cumulus cells are affected by exposure to the high levels of NEFA. Besides, the epithelial-mesenchymal transition of granulosa cells to luteal cells is also negatively affected, and the transcriptomic pattern was altered. In oocytes, the high level of NEFA impairs the nuclear maturation, inhibits FA β-oxidation, and decreases ATP content. Blastocysts originating from oocytes exposed to the high level of NEFA showed less total cell number and altered transcriptomic and DNA methylation patterns. Moreover, granulosa cells and cumulus cells protect the oocyte when they are exposed to a high fatty acid environment via reducing the quantity of NEFAs that oocyte-exposed either through lipid droplets storage or oxidization. Besides, the granulosa cells can produce and deliver some anti-inflammatory factors to cumulus cells and oocytes through the bidirectional communication. Therefore, the anti-inflammatory response exists in blastocyst originated from the high level of NEFAs-exposed oocyte.