Steroid Receptor Coregulators Can Modulate the Action of Progesterone Receptor during the Estrous Cycle in Cow Endometrium.
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ABSTRACT:
SUBMITTER: Rekawiecki R
PROVIDER: S-EPMC8614263 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Although the corpus luteum (CL) contains high concentrations of lipid in the form of steroid hormone precursors and prostaglandins, little is known about the abundance or function of other luteal lipid mediators. To address this, 79 lipid mediators were measured in bovine CL, using ultra performance liquid chromatography-tandem mass spectrometry. CL from estrous cycle days 4, 11, and 18 were compared and, separately, CL from days 18 of the estrous cycle and pregnancy were compared. Twenty-three lipids increased as the estrous cycle progressed (P < 0.05), with nine increasing between days 4 and 11 and fourteen increasing between days 4 and 18. Overall, this indicated a general upregulation of lipid mediator synthesis as the estrous cycle progressed, including increases in oxylipins and endocannabinoids. Only 15-KETE was less abundant in the CL of early pregnancy (P < 0.05), with a tendency (P < 0.10) for four others to be less abundant. Notably, 15-KETE also increased between estrous cycle days 4 and 18. Ingenuity Pathway Analysis (IPA, Qiagen) indicated that functions associated with differentially abundant lipids during the estrous cycle included leukocyte activation, cell migration, and cell proliferation. To investigate changes in CL during maternal recognition of pregnancy, this lipid dataset was integrated with a published dataset from mRNA profiling during maternal recognition of pregnancy. This analysis indicated that lipids and mRNA that changed during maternal recognition of pregnancy may regulate some of the same functions, including immune cell chemotaxis and cell-cell communication. To assess effects of these lipid mediators, luteal cells were cultured with 5-KETE or 15-KETE. One ng/mL 5-KETE reduced luteal progesterone on day 1 of culture, only in the absence of luteinizing hormone (LH), while 1 ng/mL 15-KETE induced progesterone only in the presence of LH (10 ng/mL). On day 7 of culture, 0.1 ng/mL 15-KETE reduced prostaglandin (PG)F2A-induced inhibition of LH-stimulated progesterone production, while 1 ng/mL 15-KETE did not have this effect. Overall, these data suggest a role for lipid mediators during luteal development and early pregnancy, as regulators of steroidogenesis, immune cell activation and function, intracellular signaling, and cell survival and death.
| S-EPMC6788218 | biostudies-literature
Project description:Several reports suggest the participation of progesterone receptor membrane component 1 (PGRMC1) in progesterone signaling in the reproductive system. This study aimed at investigating the presence and localization of PGRMC1 in bovine ovary, oviduct and uterus, during the follicular and luteal phases of the estrous cycle. In the ovary, PGRMC1 has been detected in surface germinal epithelium, granulosa cells, theca cells and in the germinal vesicle of the oocytes at all stages of folliculogenesis. In the corpus luteum the expression of PGRMC1 was influenced by the stage of the estrous cycle. In the oviducts and in the uterus horns, PGRMC1 was immunolocalized in the luminal epithelium, in the muscle layer cells and in the endothelial cells. In the uterus, PGRMC1 was intensely localized also in the glandular endometrium. However, in the oviducts and in the uterus horns, the localization of PGRMC1 was independent on the stage of the estrous cycle and on whether evaluating the ipsilateral or the contralateral organ. In conclusion, the present immunohistochemical study showed that PGRMC1 is located in various compartments of the bovine female reproductive organs. With the exception of the corpora lutea, PGRMC1 localization showed similar pattern during different stages of the estrous cycle.
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Project description:OBJECTIVE:Leukemia inhibitory factor (LIF) binds to a heterodimeric receptor composed of LIF receptor (LIFR) and glycoprotein 130 (GP130) to transmit signals into the cell. LIF plays an important role in reproduction by regulating immune response, decidualization, and implantation in several species. However, the expression of LIF and LIFR in the endometrium throughout the estrous cycle and pregnancy in pigs is not fully understood. METHODS:We analyzed the expression of LIF and LIFR in the endometrium on days 0 (estrus), 3, 6, 9, 12, 15, and 18 of the estrous cycle, and days 12, 15, 30, 60, 90, and 114 of pregnancy, in conceptuses on days 12 and 15, and in chorioallantoic tissues on days 30, 60, 90, and 114 of pregnancy in pigs. We also determined the effects of estrogen and progesterone on the expression of LIF and LIFR in endometrial tissues. RESULTS:The expression of LIF increased in the endometrium during the late diestrus phase of the estrous cycle and during mid- to late- pregnancy, while the expression of LIFR increased during early pregnancy. The expression of LIF was induced by increasing doses of estrogen, whereas the expression of LIFR was induced by increasing doses of progesterone. CONCLUSION:These results indicate that the expression of LIF and its receptor LIFR in the endometrium is regulated in a stage-specific manner during the estrous cycle and pregnancy, suggesting that LIF and its receptor signaling system may play critical roles in regulating endometrial function in pigs.
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Project description:Despite the importance of the mouse in biomedical research, the levels of circulating gonadal steroids across the estrous cycle are not established with any temporal precision. Using liquid chromatography-mass spectrometry, now considered the gold standard for steroid hormone analysis, we aimed to generate a detailed profile of gonadal steroid levels across the estrous cycle of C57BL/6J mice. For reference, luteinizing hormone (LH) and prolactin concentrations were measured in the same samples by sandwich ELISA. Terminal blood samples were collected at 8-hour intervals (10 am, 6 pm, 2 am) throughout the four stages of the estrous cycle. As expected, the LH surge was detected at 6 pm on proestrus with a mean (±SEM) concentration of 11 ± 3 ng/mL and occurred coincident with the peak in progesterone levels (22 ± 4 ng/mL). Surprisingly, estradiol concentrations peaked at 10 am on diestrus (51 ± 8 pg/mL), with levels on proestrus 6 pm reaching only two-thirds of this value (31 ± 5 pg/mL). We also observed a proestrous peak in prolactin concentrations (132.5 ± 17 ng/mL) that occurred earlier than expected at 2 am. Estrone and androstenedione levels were often close to the LOD and showed no consistent changes across the estrous cycle. Testosterone levels were rarely above the LOD (0.01 ng/mL). These observations provide the first detailed assessment of fluctuating gonadal steroid and reproductive hormone levels across the mouse estrous cycle and indicate that species differences exist between mice and other spontaneously ovulating species.
| S-EPMC10225909 | biostudies-literature
Project description:Caspases, a family of cysteine protease enzymes, are a critical component of apoptotic cell death, but they are also involved in cellular differentiation. The expression of caspases during apoptotic processes in reproductive tissues has been shown in some species; however, the expression and regulation of caspases in the endometrium and placental tissues of pigs has not been fully understood. Therefore, we determined the expression of caspases CASP3, CASP6, CASP7, CASP8, CASP9, and CASP10 in the endometrium throughout the estrous cycle and pregnancy. During the estrous cycle, the expression of all caspases and during pregnancy, the expression of CASP3, CASP6, and CASP7 in the endometrium changed in a stage-specific manner. Conceptus and chorioallantoic tissues also expressed caspases during pregnancy. CASP3, cleaved-CASP3, and CASP7 proteins were localized to endometrial cells, with increased levels in luminal and glandular epithelial cells during early pregnancy, whereas apoptotic cells in the endometrium were limited to some scattered stromal cells with increased numbers on Day 15 of pregnancy. In endometrial explant cultures, the expression of some caspases was affected by steroid hormones (estradiol-17β and/or progesterone), and the cytokines interleukin-1β and interferon-γ induced the expression of CASP3 and CASP7, respectively. These results indicate that caspases are dynamically expressed in the endometrium throughout the estrous cycle and at the maternal-conceptus interface during pregnancy in response to steroid hormones and conceptus signals. Thus, caspase action could be important in regulating endometrial and placental function and epithelial cell function during the implantation period in pigs.
| S-EPMC7907442 | biostudies-literature
Project description:Interferon tau (IFN-τ) is a ruminant-specific type I IFN secreted by a conceptus before its attachment to the uterus. IFN-τ induces the expression of IFN-stimulated genes (ISGs) via the type I IFN receptor (IFNAR), which is composed of IFNAR1 and IFNAR2 subunits in the endometrium. However, expression patterns of IFNARs during the estrous cycle have not been reported. We hypothesized that the response to a type I IFN changes along with IFNARs and the IFN-regulatory factors (IRFs) driving transcription of IFN signal-related genes and modulating a type I IFN signal during the estrous cycle. We investigated the estrous cycle stage-dependent type I IFN induction of ISGs and expression patterns of IFN signal-related genes in bovine endometrial tissues. Endometrial tissue pieces collected from bovine uteri at each estrous stage (early, mid, and late) were cultured with or without recombinant bovine IFN-α or concentrated pregnant uterine flushing (PUF) on day 18 after confirming the presence of a conceptus. IFN-α and PUF each significantly increased the expression of ISGs in endometrial tissues. The induction levels of the typical ISGs (MX1-a and ISG15) were significantly higher at the mid stage and correlated with high expression of IRFs at the mid stage. The immunostaining of IFNARs showed strong fluorescence intensities in luminal and glandular epithelia at the early and mid stages. Collectively, these results suggest that the endometrium exhibits estrous cycle stage-dependent responsiveness to type I IFN that may be associated with the expression of IFNARs and IRFs for pregnancy recognition.
| S-EPMC5481623 | biostudies-literature
Project description:BACKGROUND: Implantation in humans involves cross talk between an active blastocyst and receptive endometrium. The role of the endometrial receptors in this complex embryo-maternal interaction is still unclear. We tested gene and protein expression of endometrial receptors (Progesterone receptor (PR) and c-Met) and the effect of theses receptors in endometrial receptivity. METHODS: Two endometrial cell lines were used: HEC-1A and RL95-2 considered as being of low and high receptivity, respectively. Western blot and RT-PCR analysis were utilized to study the receptor expression profile.The role of endometrial receptors in endometrial receptivity was studied by attachment and invasion assays of JAR spheroids (made of a trophoblast cell line) on endometrial cells. Different manipulations of inhibition and stimulation of the endometrial receptors were used including: inhibition by specific antibodies against the receptors, or antagonist of the receptors, as well as transfection with antisense for the endometrial receptors, stimulation by specific ligands for the receptors and transfection with the gene for endometrial receptors. RESULTS: Different protein expression patterns of endometrial receptors were observed between the tested endometrial cell lines. The expression levels of PRA ratio to PRB, and the 50 kDa c-MET isoform were significantly lower in HEC-1A as compared with RL95-2. Attachment rates and growth of JAR spheroids into HEC-1A were significantly lower as compared with RL95-2. Stimulation of PR with progesterone altered attachment rates to HEC-1A. Inhibition of PR with RU-486 mildly increased attachment rate to HEC-1A whereas it slightly decreased attachment rate to RL95-2. c-Met inhibition decreased attachment rates only to HEC-1A cells that expressing high levels of Plexin-B1 (PB1). Immunoprecipitation studies revealed that c-Met and PB1 associate in complexes in the endometrial cell lines. CONCLUSION: Differential endometrial receptor profiles are expressed during the receptivity period. The attachment and invasion processes are separately regulated. We suggest a biologically functional role for PRA in endometrial receptivity and in the attachment process. c-Met contribution is minor and related with creation of a complex with PB1.
| S-EPMC2649138 | biostudies-literature
Project description:Progesterone receptor (PGR) for its action required connection of the coregulatory proteins, including coactivators and corepressors. The former group exhibits a histone acetyltransferase (HAT) activity, while the latter cooperates with histone deacetylase (HDAC). Regulations of the coregulators mRNA and protein and HAT and HDAC activity can have an indirect effect on the PGR function and thus progesterone (P4) action on target cells. The highest mRNA expression levels for the coactivators-histone acetyltransferase p300 (P300), cAMP response element-binding protein (CREB), and steroid receptor coactivator-1 (SRC-1)-and nuclear receptor corepressor-2 (NCOR-2) were found in the corpus luteum (CL) on days 6 to 16 of the estrous cycle. The CREB protein level was higher on days 2-10, whereas SRC-1 and NCOR-2 were higher on days 2-5. The activity of HAT and HDAC was higher on days 6-10 of the estrous cycle. All of the coregulators were localized in the nuclei of small and large luteal cells. The mRNA and protein expression levels of the examined coactivators and corepressor changed with the P4 level. Thus, P4 may regulate CL function via the expression of coregulators, which probably affects the activity of the PGR.
| S-EPMC7465684 | biostudies-literature
Project description:The equine endometrium exhibits characteristic morphological and functional changes during the estrous cycle controlled by the interplay of progesterone and estradiol. A microarray analysis of endometrial tissue samples derived from 5 time points of the estrous cycle (D0, D3, D8, D12, and D16) was performed to study the dynamics of endometrial gene expression. Endometrial biopsies were collected from five mares (Bavarian Warmblood) at the respective time points. Samples were divided and subjected to isolation of RNA for microarray analysis and analysis of tissue composition. Blood samples were collected to determine serum progesterone levels for every sample. Statistical analysis of microarray data revealed almost 10,000 differential probes corresponding to 4,996 differentially expressed genes. A cluster analysis based on gene expression profiles during the estrous cycle revealed 8 major gene expression profiles: mRNAs with highest levels 1) at D0, 2) from D0 to D3, 3) at D3, 4) from D3 to D8, 5) at D8, 6) from D8 to D12, 7) from D12 to D16, and 8) at D16. DAVID Functional Annotation Clustering revealed overrepresentation of distinct functional terms in different phases of the cycle, e.g. M-bM-^@M-^Xextracellular matrixM-bM-^@M-^Y and M-bM-^@M-^Xprotein transportM-bM-^@M-^Y during estrus, M-bM-^@M-^XDNA replication and M-bM-^@M-^Xcell cycleM-bM-^@M-^Y during early luteal phase, M-bM-^@M-^Xendoplasmic reticulumM-bM-^@M-^Y and M-bM-^@M-^Xprotein transportM-bM-^@M-^Y in the luteal phase, and M-bM-^@M-^Xinflammatory responseM-bM-^@M-^Y in the late luteal and follicular phase. Expression of selected genes of the expression clusters was validated by quantitative Real-time PCR (qPCR). This study provides new insights into global changes of equine endometrial gene expression during the estrous cycle. Equine endometrial tissue samples were collected at 5 time points during the sexual (estrous) cycle from 5 mares (5 biological replicates per time point) and analyzed with Agilent microarrays.
2012-10-23 | E-GEOD-39043 | biostudies-arrayexpress
Project description:Deletion of the heme oxygenase-1 (HO-1) (Hmox1) locus in mice results in intrauterine lethality. The expression of the heme catabolizing enzyme encoded by this gene, namely HO-1, is required to successfully support reproductive events. We have previously observed that HO-1 acts at several key events in reproduction ensuring pregnancy. HO-1 defines ovulation, positively influences implantation and placentation, and ensures fetal growth and survival. Here, we embarked on a study aimed to determine whether hormonal changes during the estrous cycle in the mouse define HO-1 expression that may influence receptivity. We analyzed the serum levels of progesterone and estrogen by ELISA and HO-1 mRNA expression in uterus by real time RT-PCR at the metestrus, proestrus, estrus, and diestrus phases of the estrous cycle. Further, we studied the HO-1 protein expression by western blot upon hormone addition to cultured uterine AN3 cells. We observed that HO-1 variations in uterine tissue correlated to changes in hormonal levels at different phases of the estrus cycle. In vitro, HO-1 protein levels in AN3 cells augmented after the addition of physiological concentrations of progesterone and estradiol, which confirmed our in vivo observations. Our data suggest an important role for hormones in HO-1 regulation in uterus during receptivity, a process known to have a significant impact in receptivity and later on blastocyst implantation.
| S-EPMC3952397 | biostudies-literature