Abstract:-It is well-known that indomethacin (the cyclooxygenase 1 & 2 inhibitor) and RU486 (or mifepristone, the progesterone receptor antagonist) block follicular rupture in rats. To characterize genetic alterations in unruptured follicles, gene expression profiles in ovarian follicle were analyzed in indomethacin-and RU486-treated female Sprague-Dawley rats. Ovaries are collected at 22:00 on the proestrus day and 10:00 on the following estrus day after a single dose of indomethacin and RU486. Histopathologically, ch… Show more
“…ADAMTS9 increased expression in human granulosa cells after hCG treatment (Rosewell et al., ), as well as in dominant follicle of rhesus macaques after ovulatory stimulus (Peluffo, Murphy, Baughman, Stouffer, & Hennebold, ). In progesterone receptor antagonist‐treated rats, ADAMTS9 was downregulated, resulting in a block follicular rupture (Tsubota et al., ). Further research is required to improve the current understanding of the role these proteins play in follicular development.…”
Follicular fluid (FF) accumulates in the antrum of the ovarian follicle. In addition, FF provides the microenvironment for oocyte development, oocyte maturation and competence, which are acquired during follicular development. Superstimulatory treatment of 1-month-old lambs can achieve synchronous development of numerous growing follicles. However, these growing follicles are unable to completely mature and ovulate. Furthermore, the oocytes exhibit lower competence compared with those of ewes. In this study, we utilized an isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics analysis and compare protein composition between pre-pubertal and adult superstimulated follicle FF in sheep. In total, 243 differentially expressed proteins were identified, including 155 downregulated and 88 upregulated between lamb and ewe. Gene ontology (GO) and KEGG pathway analysis indicated that the differentially expressed proteins are involved in signal transduction, anatomical structure development, stress response, metabolic pathways, and the complement and coagulation cascades. Many of the proteins known to affect follicle development were observed in lower abundance in FF of lamb (e.g. ADAMTS9, CD14, CTNNB1, FST, GCLC, HSPG2, IGFBP2, IGFBP6, INHBA, PRL, PAPPA, POSTN, PRDX1, SERPINA1, SOD3, STC1, VEGFC, etc.). However, a higher abundance was observed for proteasome proteins. Inadequate amounts of these proteins in FF may be lead to the unique characteristics of follicular development in lamb. These differentially expressed proteins illuminate the age-dependent changes in protein expression in the follicle microenvironment.
“…ADAMTS9 increased expression in human granulosa cells after hCG treatment (Rosewell et al., ), as well as in dominant follicle of rhesus macaques after ovulatory stimulus (Peluffo, Murphy, Baughman, Stouffer, & Hennebold, ). In progesterone receptor antagonist‐treated rats, ADAMTS9 was downregulated, resulting in a block follicular rupture (Tsubota et al., ). Further research is required to improve the current understanding of the role these proteins play in follicular development.…”
Follicular fluid (FF) accumulates in the antrum of the ovarian follicle. In addition, FF provides the microenvironment for oocyte development, oocyte maturation and competence, which are acquired during follicular development. Superstimulatory treatment of 1-month-old lambs can achieve synchronous development of numerous growing follicles. However, these growing follicles are unable to completely mature and ovulate. Furthermore, the oocytes exhibit lower competence compared with those of ewes. In this study, we utilized an isobaric tag for relative and absolute quantification (iTRAQ)-based proteomics analysis and compare protein composition between pre-pubertal and adult superstimulated follicle FF in sheep. In total, 243 differentially expressed proteins were identified, including 155 downregulated and 88 upregulated between lamb and ewe. Gene ontology (GO) and KEGG pathway analysis indicated that the differentially expressed proteins are involved in signal transduction, anatomical structure development, stress response, metabolic pathways, and the complement and coagulation cascades. Many of the proteins known to affect follicle development were observed in lower abundance in FF of lamb (e.g. ADAMTS9, CD14, CTNNB1, FST, GCLC, HSPG2, IGFBP2, IGFBP6, INHBA, PRL, PAPPA, POSTN, PRDX1, SERPINA1, SOD3, STC1, VEGFC, etc.). However, a higher abundance was observed for proteasome proteins. Inadequate amounts of these proteins in FF may be lead to the unique characteristics of follicular development in lamb. These differentially expressed proteins illuminate the age-dependent changes in protein expression in the follicle microenvironment.
“…LH mainly triggers the ERK1/ ERK2 signaling cascade in granulosa cells (GCs) to induce the expression of many genes crucial for ovulation, oocyte meiosis, and extracellular matrix (ECM) remodeling [1]. Many of these ERK1/ERK2-dependent genes, including AREG, ADAMTS1, and CITED2, in GCs were associated with oocyte quality and IVF outcomes [2][3][4][5][6][7].…”
Purpose The study investigated potential correlations between the expression levels of ADAMTS1 and HSPG2 in cumulus cells (CCs) and controlled ovarian hyperstimulation (COH) outcomes. Methods RT-PCR was used to determine ADAMTS1 and HSPG2 mRNA levels in mice CCs at different timepoints (0, 4, 8, 12, and 16 h) after human chorionic gonadotropin (hCG) injection, and in CCs after RNAi treatment. Women with polycystic ovary syndrome (PCOS) (n = 45) and normal ovulatory controls (n = 103) undergoing IVF/ICSI were recruited. Relative ADAMTS1 and HSPG2 mRNA levels were measured by RT-PCR. Moreover, correlations of ADAMTS1 and HSPG2 levels with COH outcomes were analyzed. Results At different timepoints after hCG treatment, ADAMTS1 mRNA had the highest level at 12 h, whereas HSPG2 showed opposite profiles to ADAMTS1 with the lowest level at 12 h. HSPG2 expression was upregulated after ADAMTS1 RNAi treatment The PCOS group had higher HSPG2 and lower ADAMTS1 expression levels than controls. In normal ovulatory women (control group), a higher expression of ADAMTS1 and lower expression of HSPG2 were associated with more mature oocytes, transplantable embryos, and good quality embryos, whereas higher transplantable embryo rates and good quality embryo rates were obtained only with lower HSPG2 expression. ROC curves showed the co-measurement of ADAMTS1 and HSPG2 had a better predictive power than separate analyses. Conclusion The dynamic profiles of ADAMTS1 and HSPG2 were inversely correlated in CCs. In PCOS and normal ovulatory patients, higher ADAMTS1 and lower HSPG2 expression levels in CCs were related to better COH outcomes.
“…In addition, some genes ( MAPK1 , BUB1 , CANA2 and IGF1) involved in the RELN pathway were down-regulated in both hCG and RU486 treatment (Additional file 3 : Table S2). These expression differences were considered relevant to the induction of ruptured and un-ruptured follicles and other features such as inflammation, tissue remodeling, extracellular matrix release, and steroid metabolism [ 2 , 7 , 17 ]. Fig.…”
Section: Resultsmentioning
confidence: 99%
“…Data were acquired from the Gene Expression Omnibus (GEO) ( http://www.ncbi.nlm.nih.gov/geo/ ) database. Two data sets, GSE54584 (this research clarified genetic alteration induced by the inhibition of cyclooxygenase or progesterone receptor) and GSE41836 (This study provided comprehensive information about regulated genes during late follicle development and ovulation induction), were contributed by Kenjiro et al [ 17 ] and Cansu et al [ 18 ], respectively. GSE41836 total contains 12 samples of cumulus oocyte complexes, among which only three samples with human Chorionic Gonadotropins (hCG) treatment were selected.…”
Section: Methodsmentioning
confidence: 99%
“…GSE41836 total contains 12 samples of cumulus oocyte complexes, among which only three samples with human Chorionic Gonadotropins (hCG) treatment were selected. GSE54584 total contains 18 samples, six samples including three samples with hCG treatment and three samples with RU486 (100 mg/kg) treatment in preovulatory were selected [ 17 , 18 ]. These selected samples were analyzed by the GEO2R ( http://www.ncbi.nlm.nih.gov/geo/geo2r/ ) with respect to the control groups (samples with same dose normal saline treatment).…”
BackgroundProgesterone plays an essential role in mammalian ovulation. Although much is known about this process, the gene networks involved in ovulation have yet to be established. When analyze the mechanisms of ovulation, we often need to determine key genes or pathways to investigate the reproduction features. However, traditional experimental methods have a number of limitations.ResultsData, in this study, were acquired from GSE41836 and GSE54584 which provided different samples. They were analyzed with the GEO2R and 546 differentially expressed genes were obtained from two data sets using bioinformatics (absolute log2 FC > 1, P < 0.05). This study identified four genes (PGR, RELN, PDE10A and PLA2G4A) by protein-protein interaction networks and pathway analysis, and their functional enrichments were associated with ovulation. Then, the top 25 statistical pathway enrichments related to hCG treatment were analyzed. Furthermore, gene network analysis identified certain interconnected genes and pathways involved in progestogenic mechanisms, including progesterone-mediated oocyte maturation, the MAPK signaling pathway, the GnRH signaling pathway and focal adhesion, etc. Moreover, we explored the four target gene pathways. q-PCR analysis following hCG and RU486 treatments confirmed the certain novel progestogenic-associated genes (GNAI1, PRKCA, CAV1, EGFR, RHOA, ZYX, VCL, GRB2 and RAP1A).ConclusionsThe results suggested four key genes, nine predicted genes and eight pathways to be involved in progestogenic networks. These networks provide important regulatory genes and signaling pathways which are involved in ovulation. This study provides a fundamental basis for subsequent functional studies to investigate the regulation of mammalian ovulation.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0577-7) contains supplementary material, which is available to authorized users.
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