Programmed necrosis - a new mechanism of steroidogenic luteal cell death and elimination during luteolysis in cows

Abstract

Programmed necrosis (necroptosis) is an alternative form of programmed cell death that is regulated by receptor-interacting protein kinase (RIPK) 1 and 3-dependent, but is a caspase (CASP)-independent pathway. In the present study, to determine if necroptosis participates in bovine structural luteolysis, we investigated RIPK1 and RIPK3 expression throughout the estrous cycle, during prostaglandin F2α (PGF)-induced luteolysis in the bovine corpus luteum (CL), and in cultured luteal steroidogenic cells (LSCs) after treatment with selected luteolytic factors. In addition, effects of a RIPK1 inhibitor (necrostatin-1, Nec-1; 50 μM) on cell viability, progesterone secretion, apoptosis related factors and RIPKs expression, were evaluated. Expression of RIPK1 and RIPK3 increased in the CL tissue during both spontaneous and PGF-induced luteolysis (P < 0.05). In cultured LSCs, tumor necrosis factor α (TNF; 2.3 nM) in combination with interferon γ (IFNG; 2.5 nM) up-regulated RIPK1 mRNA and protein expression (P < 0.05). TNF + IFNG also up-regulated RIPK3 mRNA expression (P < 0.05), but not RIPK3 protein. Although Nec-1 prevented TNF + IFNG-induced cell death (P < 0.05), it did not affect CASP3 and CASP8 expression. Nec-1 decreased both RIPK1 and RIPK3 protein expression (P < 0.05). These findings suggest that RIPKs-dependent necroptosis is a potent mechanism responsible for bovine structural luteolysis induced by pro-inflammatory cytokines.

Effects of prostaglandin F2α on angiogenic and steroidogenic pathways in the bovine corpus luteum may depend on its route of administration

“…based on previous reports that identified this as a suitable time (Mondal et al, 2011;Zalman et al, 2012;Hojo et al, 2016). Until now, however, there have been no reports indicating a clear difference in the actions of aPGF 2α on the CL with regard to local versus systemic administration.…”

“…Previous studies have examined the effect of aPGF 2α treatment on bovine CL at specific time points after its administration (Berisha et al, 2010;Hojo et al, 2016). We elected to collect CL 4 h after aPGF 2α treatment Figure 6.…”

“…Protein expression levels for FGF2, FGFR1, FGFR2, VEGFA, VEGFR1, VEGFR2, STAR, P450scc, HSD3B, and GAPDH in the tissues were determined by Western blotting as previously described (Hojo et al, 2016). Specific antibodies are described in detail in Table 2.…”

Necrosis and necroptosis in germ cell depletion from mammalian ovary

“…ACh: acetylcholine; AChE-R: read-through acetylcholinesterase; ATP: adenosine triphosphate; CYLD: cylindromatosis; DHEA: dehydroepiandrosterone; MLKL: mixed lineage kinase domain-like protein; FADD: Fas-associating protein with death domain; ROS: reactive oxygen species; RIPK1: receptor interacting protein kinase-1; RIPK3: receptor interacting protein kinase-3; TNF-α: tumor necrosis factor-α; TNFR: TNF receptor; TRADD: TNFR1-associated death domain protein, TRAF2: TNFR-associated factor 2 [Color figure can be viewed at wileyonlinelibrary.com] Wu et al, 2012). Involvement of RIPK1, RIPK3, and MLKL proteins in TNFR-mediated necroptosis have been reported in rat brain and male reproductive system of the mouse as well as in luteal cells of the cow (Hojo et al, 2016;Q. Cai et al, 2017;S.…”

Necroptosis in stressed ovary

“…Studies suggest that regulated form of necrosis so called necroptosis shows morphological features similar to necrosis [33]. A few studies indicate the occurrence of OS-mediated necroptosis in cow [34] and human ovary [35]. The OS-mediated necroptosis in granulosa cells and oocyte remains ill understood.…”