Dataset Information

Estrogen promotes luteolysis by redistributing prostaglandin F2? receptors within primate luteal cells.

ABSTRACT: Prostaglandin F2? (PGF2?) has been proposed as a functional luteolysin in primates. However, administration of PGF2? or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2? receptors (PTGFRs) or responsiveness to PGF2? at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from healthy women undergoing follicle aspiration. PTGFRs were present in the cytoplasm of monkey granulosa cells, while PTGFRs were localized in the perinuclear region of large, granulosa-derived monkey luteal cells by mid-late luteal phase. A PTGFR agonist decreased progesterone production in luteal cells obtained at mid-late and late luteal phases, but did not decrease progesterone production by granulosa cells or luteal cells from younger corpora lutea. These findings are consistent with a role for perinuclear PTGFRs in functional luteolysis. This concept was explored using human luteinizing granulosa cells maintained in vitro as a model for luteal cell differentiation. In these cells, PTGFRs relocated from the cytoplasm to the perinuclear area in an estrogen- and estrogen receptor-dependent manner. Similar to our findings with monkey luteal cells, human luteinizing granulosa cells with perinuclear PTGFRs responded to a PTGFR agonist with decreased progesterone production. These data support the concept that PTGFR stimulation promotes functional luteolysis only when PTGFRs are located in the perinuclear region. Estrogen receptor-mediated relocation of PTGFRs within luteal cells may be a necessary step in the initiation of luteolysis in primates.

SUBMITTER: Kim SO

PROVIDER: S-EPMC4380810 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells.

Kim Soon Ok SO Markosyan Nune N Pepe Gerald J GJ Duffy Diane M DM

Reproduction (Cambridge, England) 20150216 5

Prostaglandin F2α (PGF2α) has been proposed as a functional luteolysin in primates. However, administration of PGF2α or prostaglandin synthesis inhibitors in vivo both initiate luteolysis. These contradictory findings may reflect changes in PGF2α receptors (PTGFRs) or responsiveness to PGF2α at a critical point during the life span of the corpus luteum. The current study addressed this question using ovarian cells and tissues from female cynomolgus monkeys and luteinizing granulosa cells from he ...[more]

PMID: 25687410

Similar Datasets

Project description:BackgroundPGF2? is essential for the induction of the corpus luteum regression which in turn reduces progesterone production. Early growth response (EGR) proteins are Cys2-His2-type zinc-finger transcription factor that are strongly linked to cellular proliferation, survival and apoptosis. Rapid elevation of EGR1 was observed after luteolytic dose of PGF2?. EGR1 is involved in the transactivation of many genes, including TGF?1, which plays an important role during luteal regression.MethodsThe current study was conducted in buffalo luteal cells with the aim to better understand the role of EGR1 in transactivation of TGF?1 during PGF2? induced luteal regression. Luteal cells from mid stage corpus luteum of buffalo were cultured and treated with different doses of PGF2? for different time durations. Relative expression of mRNAs encoding for enzymes within the progesterone biosynthetic pathway (3?HSD, CYP11A1 and StAR); Caspase 3; AKT were analyzed to confirm the occurrence of luteolytic event. To determine if EGR1 is involved in the PGF2? induced luteal regression via induction of TGF?1 expression, we knocked out the EGR1 gene by using CRISPR/Cas9.ResultThe present experiment determined whether EGR1 protein expression in luteal cells was responsive to PGF2? treatment. Quantification of EGR1 and TGF?1 mRNA showed significant up regulation in luteal cells of buffalo at 12 h post PGF2? induction. In order to validate the role of PGF2? on stimulating the expression of TGF?1 by an EGR1 dependent mechanism we knocked out EGR1. The EGR1 ablated luteal cells were stimulated with PGF2? and it was observed that EGR1 KO did not modulate the PGF2? induced expression of TGF?1. In PGF2? treated EGR1 KO luteal cell, the mRNA expression of Caspase 3 was significantly increased compared to PGF2? treated wild type luteal cells maintained for 12 h. We also studied the influence of EGR1 on steroidogenesis. The EGR1 KO luteal cells with PGF2? treatment showed no substantial difference either in the progesterone concentration or in StAR mRNA expression with PGF2?-treated wild type luteal cells.ConclusionThese results suggest that EGR1 signaling is not the only factor which plays a role in the regulation of PGF2? induced TGF?1 signaling for luteolysis.

Project description:BACKGROUND:Prostaglandin F2? (PGF2?) is an important component for the physiology of female reproductive processes. In the literature, the data pertaining to the synthesis and action of PGF2? in early embryonic bovine development are limited. In our study, we used the bovine in vitro culture model based on the time of first cleavage to determine the mRNA expression and immunolocalization of PGF2? synthase and its receptor in bovine embryos from the 2-cell stage to the hatched blastocyst stage. We also evaluated PGF2? production at 2, 5 and 7?days of in vitro culture. RESULTS:We found a significantly higher proportion of blastocysts obtained from the early-cleaved embryos than from the late-cleaved embryos (37.7% vs. 26.1% respectively, P?<?0.05). The PGFS mRNA expression was significantly higher in the late-cleaved group than in the early-cleaved group at the 2-, 4- and 16-cell stages (P?<?0.05). For PTGFR, we observed that within the late-cleaved group, the mRNA abundance was significantly higher in embryos at the 2- and 16-cell stages than in embryos at the 4- and 8-cell stages (P?<?0.05). We observed that PTGFR mRNA expression was significantly higher in the 2- and 16-cell embryos in the late-cleaved group than that in the early-cleaved group embryos (P?<?0.05). Among the blastocysts, the PGFS and PTGFR expression levels showed a trend towards higher mRNA expression in the late-cleaved group than in the early-cleaved group. Analysis of PGF2? production showed that within the early-cleaved group, the content of PGF2? in the in vitro culture medium was significantly higher on day 7 than it was on day 2 (P?<?0.05). CONCLUSIONS:The mRNA expression levels of PGF2? synthase and its receptor depend on the developmental stage and the embryo quality. Analyses of PGFS and PTGFR expression in bovine blastocysts and of PGF2? embryo production suggest that prostaglandin F2? can act in an autocrine and paracrine manner in bovine in vitro-produced preimplantation embryos. Moreover, the tendency of PTGFR and PGFS mRNA expression to be upregulated in embryos with low developmental potential can indicate a compensation mechanism related to high PGFS and PTGFR mRNA expression levels in low-quality embryos.

Dataset Information

Estrogen promotes luteolysis by redistributing prostaglandin F2? receptors within primate luteal cells.

Publications

Estrogen promotes luteolysis by redistributing prostaglandin F2α receptors within primate luteal cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets