Effects of prostaglandin F2[alpha]

Background Prostaglandin F.sub.2[alpha] (PGF.sub.2[alpha]) may differentially affect viability of luteal cells by inducing either proliferation or cell death (via apoptosis or necroptosis). The diverse effects of PGF.sub.2[alpha] may depend on its local vs. systemic actions. In our study, we determi...

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Published in:BMC veterinary research 2019-11, Vol.15 (1)
Main Authors: Jonczyk, Agnieszka Walentyna, Piotrowska-Tomala, Katarzyna Karolina, Skarzynski, Dariusz Jan
Format: Article
Language:English
Subjects:
Analysis
Apoptosis
Beef cattle
Biochemistry
Cattle
Cell death
Dinoprost
Genes
Genetic research
Immunohistochemistry
Lymphomas
Messenger RNA
Oophorectomy
Prostaglandins
Protein kinases
RNA
Tumors
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Summary:Background Prostaglandin F.sub.2[alpha] (PGF.sub.2[alpha]) may differentially affect viability of luteal cells by inducing either proliferation or cell death (via apoptosis or necroptosis). The diverse effects of PGF.sub.2[alpha] may depend on its local vs. systemic actions. In our study, we determined changes in expression of genes related to: (i) apoptosis: caspase (CASP) 3, CASP8, BCL2 associated X (BAX), B-cell lymphoma 2 (BCL2) and (ii) necroptosis: receptor-interacting protein kinase (RIPK) 1, RIPK3, cylindromatosis (CYLD), and mixed lineage kinase domain-like (MLKL) in the early and mid-stage corpus luteum (CL) that accompany local (intra-CL) vs. systemic (i.m.) analogue of PGF.sub.2[alpha] (aPGF.sub.2[alpha]) actions. Cows at day 4 (n = 24) or day 10 (n = 24) of the estrous cycle were treated by injections as follows: (1) systemic saline, (2) systemic aPGF.sub.2[alpha] (25 mg; Dinoprost), (3) local saline, (4) local aPGF.sub.2[alpha] (2.5 mg; Dinoprost). After 4 h, CLs were collected by ovariectomy. Expression levels of mRNA and protein were investigated by RT-q PCR, Western blotting and immunohistochemistry, respectively. Results We found that local and systemic administration of aPGF.sub.2[alpha] in the early-stage CL resulted in decreased expression of CASP3 (P < 0.01), but CASP8 mRNA expression was up-regulated (P < 0.05). However, the expression of CASP3 was up-regulated after local aPGF.sub.2[alpha] treatment in the middle-stage CL, whereas systemic aPGF.sub.2[alpha] administration increased both CASP3 and CASP8 expression (P < 0.01). Moreover, we observed that both local and systemic aPGF.sub.2[alpha] injections increased RIPK1, RIPK3 and MLKL expression in the middle-stage CL (P < 0.05) while CYLD expression was markedly higher after i.m. aPGF.sub.2[alpha] injections (P < 0.001). Moreover, we investigated the localization of necroptotic factors (RIPK1, RIPK3, CYLD and MLKL) in bovine CL tissue after local and systemic aPGF.sub.2[alpha] injections in the bovine CL. Conclusion Our results demonstrated for the first time that genes related to cell death pathways exhibit stage-specific responses to PGF.sub.2[alpha] administration depending on its local or systemic actions. Locally-acting PGF.sub.2[alpha] plays a luteoprotective role by inhibiting apoptosis and necroptosis in the early CL. Necroptosis is a potent mechanism responsible for structural CL regression during PGF.sub.2[alpha]-induced luteolysis in cattle. Keywords: Necroptosis, RIPKs,
ISSN:1746-6148
1746-6148
DOI:10.1186/s12917-019-2167-3