Lipotoxicity is characterized by excessive saturated fatty acids in the blood, increasing storage in non-adipose cells, which leads to changes in the expression pattern of genes related to endoplasmic reticulum stress (e.g., ATF4, ATF6, CHOP, and GRP78), pro- and anti-apoptotic pathways (e.g., Bax and Bcl-2, and protein stability, including heat shock proteins, e.g., HSP70). A negative sub-cellular effect is usually an end result, which also occurs in the ovarian follicular population, affecting granulosa cells and cumulus-oocyte complexes (COCs), which leads to a decrease in oocyte quality and mitochondrial activity, and increased apoptosis. The addition of high doses of non-esterified fatty acids to oocyte in vitro maturation medium has been shown to slow the progression of meiosis, hampering oocyte maturation and subsequent in vitro embryo development. Due to its importance in the control of cellular lipid droplets and expression correlation with cytosolic lipid accumulation, the expression of the Plin 2 (Perilipin 2) protein is also highlighted. The aim of this review is to discuss some reproductive implications of dietary lipid supplementation in ruminant females, and the potential effects of lipotoxicity on oocyte quality and reproduction, and the main mechanisms involved in the expression of genes related to endoplasmic reticulum stress and cellular lipid accumulation