Long-acting injectable progesterone (P4) supplementation at the onset of diestrous increases the conception rate of beef cows. However, the anticipation of functional and structural regression of the corpus luteum (CL; i.e. anticipated luteolysis) has been observed, resulting in subsequent pregnancy loss in 30-50% of animals subjected to this treatment, reducing the efficacy of P4-supplementation strategy. To explain the occurrence of anticipated luteolysis in P4-supplemented cows, two non-exclusive hypothesis were formulated: (1) the early release of endometrial prostaglandin F2-alpha (PGF2±) luteolytic pulses and (2) the formation of a sub-functional CL lead to an anticipated luteolysis. The general objective is to comprehend and manipulate the endocrine, molecular, endometrial and luteal mechanisms associated with anticipated luteolysis in beef cattle treated with long-acting P4 at diestrous. Cyclic multiparous Nelore (Bos indicus) cows will be submitted to a hormonal protocol to have their ovulations synchronized and will receive placebo or injectable long-acting P4 at the beginning of diestrous. The follicular growth, growth and vascularization of luteal tissue will be evaluated by ultrasonography and P4 plasma concentration will be measured by radioimmunoassay. Endometrial samples will be collected with cytological brushes and luteal samples by biopsy. Transcripts will be measured by qPCR. The aim of Experiment 1 is to evaluate the progressive dynamics of gene expression that (1) control [e.g., progesterone receptor (PGR), estrogen receptor 1 (ESR1), estrogen receptor 2 (ESR2), oxytocin receptor (OXTR)] and promotes PGF2± release at the endometrium [eg, phospholipase A2, group X (PLA2G10), prostaglandin-endoperoxidase synthase 2 (PTGS2) aldo-keto reductase family 1, member B1 (AKR1B1) aldo-keto reductase family 1, member C3 (AKR1C3) , aldo-keto reductase family 1, member C4 (AKR1C4), carbonyl reductase 1 (CBR1)] and (2) genes associated with the development [vascular endothelial growth factor A (VEGFA), fibroblast growth factor 2 (FGF2), fms-related tyrosine kinase 1 (FLT1), kinase insert domain receptor (KDR), luteinizing hormone / choriogonadotropin receptor (LHCGR)], operation [steroidogenic acute regulatory protein (STAR), hydroxy-delta-5-steroid dehydrogenase, 3-beta-and steroid delta-isomerase 4 (HSD3B4), cytochrome P450, family 11, subfamily a, polypeptide 1 (CYP11A1), nuclear receptor subfamily 5, group A, member 1 (NR5A1), peripheral benzodiazepine receptor-; PBR)] and response to PGF2± [PTGS2, prostaglandin-F synthase (PTGFS), prostaglandin F receptor (PTGFR), FBJ murine osteosarcoma viral oncogene homology (FOS), proto-oncogene jun (JUN), early growth response 1 (EGR1) , Hydroxyprostaglandin dehydrogenase 15 - NAD (HPGD), Fas (FAS), Fas - Ligand (FASLG), interleukin 1 beta (IL1B), interleukin 8 (IL8), nuclear receptor subfamily 1, group H, member 3 (NR1H3) nuclear receptor subfamily 1, group H, member 2 (NR1H2), ATP binding cassette subfamily 1, ABCA1) in CL during the diestrous. In Experiment 2 the aim is to evaluate the effect of estradiol (E2) during proestrous in the modulation of the expression of the same genes listed in Experiment 1 and at the occurrence of anticipated luteolysis. After post-doctoral training is expected that the candidate will be acquired substantial training in molecular and endocrine aspects of the control of luteolysis in cattle. It is also expected that the understanding of this process will give base to search new ways to improve the use of P4 supplementation on early diestrous, improving results in fertility.
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