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

Abstract

Prostaglandin (PG) F 2α and its analogs (aPGF 2α) are used to induce regression of the corpus luteum (CL); their administration during the middle stage of the estrous cycle causes luteolysis in cattle. However, the bovine CL is resistant to the luteolytic actions of aPGF 2α in the early stage of the estrous cycle. The mechanisms underlying this differential luteal sensitivity, as well as acquisition of luteolytic sensitivity by the CL, are still not fully understood. Therefore, to characterize possible differences in response to aPGF 2α administration, we aimed to determine changes in expression of genes related to (1) angiogenesis-fibroblast growth factor 2 (FGF2), fibroblast growth factor receptor 1 (FGFR1), fibroblast growth factor receptor 2 (FGFR2), vascular endothelial growth factor A (VEGFA), vascular endothelial growth factor receptor 1 (VEGFR1), vascular endothelial growth factor receptor 2 (VEGFR2); and (2) steroidogenesis-steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (P450scc), and hydroxy-delta-5-steroid dehydrogenase, 3 β-and steroid delta-isomerase 1 (HSD3B) in early-and middle-stage CL that accompany local (intra-CL) versus systemic (i.m.) aPGF 2α injection. Cows at d 4 (early stage) or d 10 (middle stage) of the estrous cycle were treated as follows: (1) systemic saline injection, (2) systemic aPGF 2α injection (25 mg), (3) local saline injection, and (4) local aPGF 2α injection (2.5 mg). Progesterone (P 4) concentration was measured in jugular vein blood samples during the entire set of experiments. After 4 h of treatment, CL were collected by ovariectomy, and mRNA and protein expression levels were determined by reverse transcription quantitative-PCR and Western blotting, respectively. Local and systemic aPGF 2α injections upregulated FGF2 expression but decreased expression of VEGFA in both CL stages. Both aPGF 2α injections increased the expression of STAR in earlystage CL, but downregulated it in middle-stage CL. In the early-stage CL, local administration of aPGF 2α upregulated HSD3B, whereas systemic injection decreased its mRNA expression in early-and middle-stage CL. Moreover, we observed a decrease in the P 4 level earlier after local aPGF 2α injection than after systemic administration. These results indicate that aPGF 2α acting locally may play a luteotrophic role in early-stage CL. The systemic effect of aPGF 2α on the mRNA expression of genes participating in steroidogenesis seems to be more substantial than its local effect in middle-stage CL.

Comparison of Intra-CL Injection and Peripheral Application of Prostaglandin F2α Analog on Luteal Blood Flow and Secretory Function of the Bovine Corpus Luteum

“…Besides IM administration of PGF 2α analogs, their subcutaneous injection (SC) in the cervical area, or SC injection in the ischio-rectal fossa have also produced declines in P 4 concentration, inducing luteolysis in the cow (40,50,51). Recently, we have noted that intra-CL injection of dinoprost reduced P 4 levels at 4 h in the middle-stage CL, whereas it did not change P 4 profiles in the early-stage CL (22). Moreover, peripheral application of PGF 2α analogs may be subject to side effects, and may have actions that differ from natural PGF 2α (38,(52)(53)(54).…”

“…Quantitative real-time PCR (RT-qPCR) assays were performed in an ABI 7900 HT sequence detection system using SYBR Green PCR master mix (Applied Biosystems, Foster City, CA, USA). The sequences for bovine glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-actin (ACTB), 18S ribosomal RNA (RN18S1), STAR, P450scc, HSD3B, RIPK1, and RIPK3 were reported previously by Jonczyk et al (22,23). All primers were synthesized by Sigma-Aldrich (Custom Oligos Sigma-Aldrich, Haverhill, United Kingdom).…”

“…Prostaglandin (PG) F 2α exerts stage-specific actions on bovine CL development, maintenance, and regression (15)(16)(17)(18). During early luteal phase, PGF 2α may act as a luteo-supporting factor (18)(19)(20) and play a luteoprotective role (21)(22)(23). Uterine PGF 2α is necessary to induce luteolysis on days 17-18 of the estrous cycle in cattle, and initiates a new reproductive cycle (1,(24)(25)(26)(27).…”

“…( 35 – 37 ). Moreover, our previous study has demonstrated that intra-CL vs. intramuscular (IM) administration of PGF 2α differentially affects P 4 secretion, modulating the main genes involved in angiogenic, steroidogenic, and cell death pathways in bovine CL ( 22 , 23 ).…”

Death Processes in Bovine Theca and Granulosa Cells Modelled and Analysed Using a Systems Biology Approach

“…Studies have shown that the apoptotic process occurs in the early- and middle-stage bovine corpus luteum (CL) [ 41 ] and in bovine granulosa cells [ 40 ]. Sinderewicz et al [ 40 ] demonstrated an increase in factors involved in cell apoptosis, e.g., CASP8 of the atretic follicles compared to the healthy follicles.…”