Endometrial transcriptomic responses associated with a 17α-hydroxyprogesterone caproate-containing formulation and progesterone in Holstein cows: an exploratory RNA-seq analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Bos taurus
PROVIDER: GSE334702 | GEO | 2026/06/16
REPOSITORIES: GEO
Similar Datasets
Project description:G-protein-coupled receptors (GPCRs) mediate most cellular responses to hormones, neurotransmitters as well as environmental stimulants. However, whether GPCRs participate in modulation of tissue homeostasis through ferroptosis remains unclear. By GPCR cDNA library screening, here we identify that GPR56/ADGRG1 remodels ferroptosis plasticity. Loss of GPR56 sensitizes cells to ferroptosis and deficiency of GPR56 deteriorates ferroptosis-mediated liver injury induced by Doxorubicin (DOX) or ischemia-reperfusion (IR). Mechanistically, GPR56 decreases the abundance of phospholipids containing free polyunsaturated fatty acids (PUFAs) by promoting endocytosis-lysosomal degradation of CD36. By screening a panel of steroid hormones, we identified that 17α-hydroxypregnenolone (17-OH PREG) acts as an agonist of GPR56 to antagonize ferroptosis and efficiently attenuates liver injury before or after insult. Moreover, disease associated GPR56 mutants were unresponsive to 17-OH PREG activation and insufficient to defend against ferroptosis. Together, our findings uncover that 17-OH PREG-GPR56 axis-mediated signal transduction works as a new anti-ferroptotic pathway to maintain liver homeostasis, providing novel insights into the potential therapy for liver injury.
2026-01-15 | GSE274998 | GEO
Project description:Purpouse: The aim was evaluated the impact of estradiol cypionate (ECP) supplementation at the onset of a proestrus [i.e. at progesterone (P4) device removal of the synchronization of ovulation protocol] on the global endometrial gene expression of suckled anestrous beef cows Methods: A total of 12 suckled cows presenting absence of corpus luteum detected by ultrasound received 2 mg of estradiol benzoate im and an intravaginal P4 device. Eight days later, P4 devices were removed, and the cows received 500 mg of sodium cloprostenol IM. Cows were blocked according to body condition score and the diameter of largest follicle (LF) at P4 device removal and were randomly assigned to receive an im treatment with 1mg of ECP (ECP, n=6) or not (CON, n=6) at the P4 device removal. All cows received 10μg of buserelin acetate 48 h after the P4 device removal and were timed artificially inseminated immediately after. Cows presenting a new corpus luteum formed 6 d after the GnRH treatment had an endometrial fragment collected by transcervical biopsy Results: The integrated analysis was performed using DAVID database. A total of 135 transcripts were differentially expressed between ECP and CON groups, of which 73 genes were up regulated by ECP suplmentation and 62 genes in the CON cows. Two pathways were overrepresented by the ECP-induced transcripts: pathways in cancer (n=5 genes) and small cell lung cancer (n=3 genes). On the other hand, ECP-inhibited transcripts indicated the enrichment of three pathways: Parkinson’s disease (n=3 genes), oxidative phosphorylation (n=3 genes) and Alzheimer’s disease (n=3 genes). More specifically, ECP-induced transcripts associated with pathways in cancer [gene symbol (fold change); respectively] were LAMC3 (1.55), PTCH1 (1.51), PTCH2 (1.52), PIK3R3 (1.22) and PIAS1 (1.18), whereas ECP-inhibited transcripts associated with oxidative phosphorylation were ATP5F1 (1.18), ATP5J (1.24) and NDUFB3 (1.37). Conclusion: The ECP supplementation at onset of the synchronized proestrous slightly alters the uterine transcriptome.
2017-12-05 | GSE67807 | GEO
Project description:Endometrial transcriptomic responses associated with a 17α-hydroxyprogesterone caproate-containing formulation and progesterone in Holstein cows: an exploratory RNA-seq analysis
| PRJNA1476196 | ENA
Project description:Pregnancy loss is a significant problem when embryos produced in vitro are transferred to a synchronized uterus. Currently, mechanisms that underly losses of in vitro produced embryos during implantation are largely unknown. We investigated this problem using cattle (Bos taurus) as a biomedical model of conceptus attachment by analyzing transcriptome data of paired extraembryonic membrane and endometrial samples collected on gestation days 18 and 25, which spans the attachment window in cattle.
2023-05-17 | GSE232489 | GEO
Project description:Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 μM) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis. We compared early (6-h), intermediate (48-h), and late (14-day) in vitro whole-genome responses of hESF from women with endometriosis (hESFendo) to hESF from women without endometriosis (hESFnonendo) treated with P4 plus E2 (E2P4), E2 alone, or vehicle alone. Using this experimental paradigm, the data demonstrate unique phenotypes, gene expression processes, biochemical and signaling pathways, and networks suggestive of early, intermediate, and late responses of hESFnonendo and hESFendo to P4, giving insights into the complexity of events occurring normally in response to P4 and in the setting of endometriosis.
2012-01-24 | E-GEOD-35287 | biostudies-arrayexpress
Project description:An increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers. Endometiral samples were taken from estrous synchronized beef heifers that were either cyclic or confirmed pregnant with either normal or high concentrations of progesterone on Day 5, 7, 13 and 16 of the estrous cycle/early pregnancy.
2011-10-17 | E-GEOD-33030 | biostudies-arrayexpress
Project description:The data comes from a study, where three-spined sticklebacks (Gasterosteus aculeatus) were exposed to di-n-butyl phthalate (DBP) and 17α ethinyl-oestradiol (EE2) at nominal concentrations 35 μg/L and 40 ng/L, respectively, for four days. The aim of the study was to obtain insight into the acute transcriptional responses putatively associated with endocrine disruption. RNA samples from the testes of eight individuals fish per treatment (including solvent controls, exposed only to DMSO) were used in the microarray analysis, covering the expression of approximately 21000 genes.
2015-10-10 | E-MTAB-3951 | biostudies-arrayexpress
Project description:Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 μM) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis.
2012-01-24 | GSE35287 | GEO
Project description:An increase in circulating progesterone (P4) concentrations is associated with increased pregnancy success in beef and dairy cattle. Our objective was to ascertain differential effects of elevated P4 concentrations following conception on endometrial gene expression in beef heifers on Days 5, 7, 13 and 16 of pregnancy, corresponding to the morula, blastocyst, elongation and maternal recognition of pregnancy stages, respectively. Estrus was synchronized in beef heifers (N=263). Two-thirds (N=140) were inseminated (Day 0), and all animals were randomly assigned to one of the following treatments: (i) pregnant, high P4; (ii) pregnant, normal P4; (iii) cycling, high P4; (iv) and cycling, normal P4. All high P4 groups received a P4 release intravaginal device (PRID) on Day 3 post-estrus/mating. Tissue was collected on Days 5, 7, 13 or 16 of the cycle or pregnancy, and pregnancy was confirmed by the presence of an appropriately developed embryo/conceptus. PRID insertion elevated (P<0.05) P4 concentrations from Day 3.5 to 8 compared with untreated animals and conceptus size was larger (P<0.05) in animals with elevated P4 on Days 13 and 16 compared with normal P4. Total RNA was extracted from predominantly intercaruncular endometria from the ipsilateral uterine horn. Samples from individual heifers were selected on the basis of their P4 profiles and gene expression was analyzed using bovine Affymetrix microarrays (N=5 per treatment per time point). Microarray data from analyses using Bioconductor GCRMA and Limma packages were subjected to a modified t-test and P-values were adjusted for multiple testing using the Benjamin and Hochberg false discovery rate method. Differentially expressed genes were selected on the basis of an adjusted P-value of <0.01. There were no detectable differences in gene expression in endometria from pregnant and cyclic heifers on Days 5, 7 and 13 post-estrus, but, the expression of 764 genes was altered due to the presence of the conceptus at maternal recognition of pregnancy (Day 16). On Days 5 and 7, elevated P4 in pregnant heifers, altered the expression of 36 and 124 genes respectively but on Days 13 and 16 there were relatively few DEG between high and normal P4 heifers (15 and 25). Of the genes that were differentially regulated by P4, the majority were unique to a specific day of the estrous cycle/early pregnancy. In conclusion, gene expression in endometria did not differ between pregnant and cycling heifers until Day 16 of pregnancy (i.e. the time of maternal recognition of pregnancy and production of interferon tau by conceptus trophectoderm); however, elevating P4 in early pregnancy programmed changes in gene expression in endometria that are hypothesized to impact early conceptus growth and development. Thus, on Days 5, 7 and 13 differential gene expression was affected by P4, but on Day 16 the conceptus primarily influenced gene expression in uterine endometria of heifers.
2011-10-18 | GSE33030 | GEO
Project description:Understanding how P4 signaling occurs in endometrial cells is important to guide the development of more effective therapeutic approaches to the numerous reproductive diseases caused by disrupted P4 signaling, resulting in subfertility or infertility (Bunch et al., 2013; Kim et al., 2013; Zhang and Murphy, 2014; Szekeres-Bartho, 2018; Hirota, 2019; Liao et al., 2019). Here, to fill these knowledge gaps, we characterized endometrial PGRMC2 expression throughout the human menstrual cycle and in hEnSCs subjected to an in vitro model of human endometrial decidualization. Additionally, we describe the functional implications of PGRMC2 with a silencing approach assay, integrating RNA-seq and proteomic techniques. We evaluated the functional implication of PGRMC2 in the embryo implantation process with an outgrowth in vitro model. Finally, we also compared endometrial PGRMC2 expression with PGRMC1 and PGR.
2024-06-22 | PXD048494 | Pride