Fig. 1

Pathological conditions, environmental pollutants, starvation and lifestyle changes generate stress in the body. Stress increases extracellular ROS production from macrophages, OS and cytokines level in the granulosa cell of mammalian ovary. Stress as well as enhanced OS generates TNF-α that binds to its receptor present on the granulosa cell membrane and induces conformational changes that results a binding of TRADD with death domain of a receptor. TRADD recruits RIPK1 as well as TRAF2 forming complex-I. CYLD deubiquitinates RIPK1 allowing complex-I to dissociate from membrane. Complex-I moves into cytoplasm and associates with FADD as well as caspase-8 forming complex-II. Complex-II is responsible for the induction of apoptosis. Inhibition of caspase-8 allows the formation of necrosome and association of RIPK1 with RIPK3 that induce autophosphorylation of RIPK1 as well as RIPK3. RIPK1-RIPK3 complex phosphorylates MLKL that triggers damage of cell membrane resulting in necroptosis. Granulosa cell death deprives oocyte from survival factor, nutrients and cyclic nucleotides that lead to generation of ROS and thereby OS. The OS as well as increased level of intracellular calcium triggers oocyte necroptosis following a similar pathway as described for granulosa cell necroptosis