In-depth analysis of transcriptomes in ovarian cortical follicles from children and adults reveals interfollicular heterogeneity [RNA-Seq 2]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE241982 | GEO | 2024/06/26
REPOSITORIES: GEO
Similar Datasets
Project description:The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages.
2024-06-26 | GSE241983 | GEO
Project description:The ovarian cortical reserve of follicles is vital for fertility. Some medical treatments are toxic to follicles, leading to premature ovarian insufficiency. Ovarian tissue cryopreservation is an established method to preserve fertility in adults and even applied in prepuberty despite unproven efficacy. Here, we analyze transcriptomes of 120 cortical follicles from children and adults for detailed comparison. We discover heterogeneity with two main types of follicles in both age groups: one with expected oocyte-granulosa profiles and another with predicted role in signaling. Transcriptional changes during growth to the secondary stage are similar overall in children and adults, but variations related to extracellular matrix, theca cells, and miRNA profiles are found. Notably, cyclophosphamide dose correlates with interferon signaling in child follicles. Additionally, morphology alone is insufficient for follicle categorization suggesting a need for additional markers. Marker genes for early follicle activation are determined. These findings will help refine follicular classification and fertility preservation techniques across critical ages.
2024-06-26 | GSE241981 | GEO
Project description:A key transition in ovarian follicular development is the activation of resting primordial follicles to the growing primary follicle stage. The signals that regulate activation are still not well understood, especially in non-rodent species. we combined a microarray approach with an in vitro system to gain insight into the regulation of follicle activation. Genes and pathways identified in this study provide interesting candidates for further investigation of mechanisms underlying follicle activation. Fetal bovine ovarian cortical pieces enriched for primordial or primary follicles were obtained by culture with cotrol medium supplemented with TS+ (transferrin, selenous acid, BSA, and linoleic acid) or with insulin (ITS+), a factor that stimulate bovine follicle activation. Total RNA was extracted. Differences in global gene expression profiles between pieces enriched for primordial or primary follicles were determined by microcarray analysis.
2015-10-31 | E-GEOD-69094 | biostudies-arrayexpress
Project description:Ovarian follicle selection plays an important role in the reproduction of sexually mature hens, and this process can directly affect the growth and development of follicles until the final ovulation, thus affecting laying performance and fecundity of hens. In the laying hen ovary, one follicle from a cohort of 8-13 follicles of 6-8 mm in diameter is selected daily to enter the preovulatory hierarchy. In this study, we globally compared the proteomes of chicken ovarian follicles before and after follicle selection. A total of 5883 proteins were identified in the proteomes of chicken 6-8 mm prehierarchical follicles and 12-15 mm hierarchical follicles. 259 proteins are differentially expressed in 12-15 mm hierarchical follicle compared with prehierarchical follicle, of which 175 proteins are up-regulated and 84 proteins are down-regulated. The Gene Ontology enrichment of differentially expressed proteins revealed enriched GO terms for peptidase activity, acrosin binding for their molecular function and in the process of negative regulation of peptidase activity, and regulation of fertilization. The KEGG pathway analysis indicated that differentially expressed proteins were enriched for ribosome, lysine degradation, and endocytosis pathways. Nine differentially expressed proteins including vitellogenin-1 were validated with Parallel Reaction Monitoring (PRM) analysis, and their functions were discussed. This study provided a global proteomic view of the development of chicken ovarian follicles, which will serve as a foundation for understanding the molecular signatures and pathways of follicle selection in hens.
2021-09-08 | PXD011470 | Pride
Project description:Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells. Experiment Overall Design: RNA samples from two control groups (pooled untreated cultured ovaries) are compared to two treated groups (pooled cultured ovaries treated with GDNF)
2008-06-11 | E-GEOD-11133 | biostudies-arrayexpress
Project description:Female fertility is determined in part by the size and development of the primordial follicle pool. The current study investigates the role of glial cell-line derived neurotrophic factor (GDNF) in the regulation of primordial follicle development in the ovary. Ovaries from four-day old female rat pups were maintained in organ culture for ten days in the absence (control) or presence of GDNF or kit ligand/stem cell factor (KL). Ovaries treated with GDNF contained a significant increase in developing follicles, similar to that observed with KL treatment previously shown to promote follicle development. The actions of GDNF on the ovarian transcriptome were investigated with a microarray analysis. Immunohistochemical studies demonstrated that GDNF is localized to oocyte cytoplasm in follicles of all developmental stages, as well as to cumulus granulosa cells and theca cells in antral follicles. GDNF receptor alpha 1 (GFRalpha1) staining was localized to oocyte cytoplasm of primordial and primary follicles, and at reduced levels in oocytes of antral follicles. GFRalpha1 was present in mural granulosa cells of antral follicles, theca cells, and the ovarian surface epithelium. The localization studies were confirmed with molecular analysis. Microarray analysis was used to identify changes in the ovarian transcriptome and further elucidate the signaling network regulating early follicle development. Observations indicate that GDNF promotes primordial follicle development and mediates autocrine and paracrine cell-cell interactions required during folliculogenesis. In contrast to the testis, ovarian GDNF is predominantly produced by germ cells (oocytes) rather than somatic cells. Keywords: expression analysis, glial derived neurotrophic factor, follicle transition, ovary
2008-04-11 | GSE11133 | GEO
Project description:Previous studies have suggested that adamts9 (a disintegrin and metalloprotease with thrombospondin type-1 motifs, member 9), an extracellular matrix (ECM) metalloprotease, participates in primordial germ cell (PGC) migration and necessary for female fertility. In this study, we found that adamts9 knockout (KO) led to reduced body size, and female to male sex conversion in adult mature zebrafish prior to or after 90 days post fertilization (dpf); however, primary sex determination was not affected in early juveniles of adamts9 KO at 35 dpf. Overfeeding and lowering the rearing density rescued growth defects in female adamts9 KO fish but did not rescue defects in ovarian development in adamts9 KO. Delayed PGC proliferation, significantly reduced number and size of Stage IB follicles (equivalent to primary follicle) in early juveniles of adamts9 KO, and arrested development at Stage IB follicles in mid- or late-juveniles of adamts9 KO are likely causes of female infertility and sex conversion. Via RNAseq, we found significant enrichment of differentially expressed genes involved in ECM organization during sexual maturation in ovaries of wildtype fish; and significant dysregulation of these genes in adamts9 KO ovaries. RNAseq analysis also showed enrichment of inflammatory transcriptomic signatures in adult ovaries of these adamts9 KO. Taken together, our results indicate that adamts9 is critical for development of primary ovarian follicles and maintenance of female sex in zebrafish, and loss of adamts9 in zebrafish leads to ovarian follicle arrest, female infertility, and sex conversion in late juveniles and mature adults.
2024-04-16 | GSE264143 | GEO
Project description:Dibutyl phthalate (DBP), di-2-ethylhexyl phthalate (DEHP), and benzyl butyl phthalate (BBP) are three phthalates commonly found in consumer products, including the plastic coating of pharmaceuticals and personal care products. Folliculogenesis, a tightly regulated process occurring in the ovary, is the maturation of an immature primordial follicle to a mature antral follicle. Follicles house the oocyte and antral follicles specifically play a crucial role in ovarian steroidogenesis and ovulation. DBP, BBP, and DEHP have been associated with inhibited antral follicle growth in vitro, decreased ovulation rates in vitro, and decreased antral follicle counts in women. However, little is known about the effects of a three-phthalate mixture on antral follicles in vivo. The objective of this study was to evaluate the effects of a human relevant mixture of DBP, BBP, and DEHP on ovarian follicles through proteome profiling analysis. CD-1 female mice (60 days old) were pipet fed tocopherol stripped corn oil (vehicle control) only or a phthalate mixture (52% DBP, 36% DEHP, and 12% BBP dissolved in vehicle) which modeled human follicular fluid concentrations. The mice were treated with 32µg/kg/day (PHT Mix 32; cumulative estimate in general population) and 500µg/kg/day (PHT Mix 500; cumulative estimate in occupationally exposed individuals) for 10 consecutive days. Proteome profiling of antral follicles (>250µm) was performed via label-free tandem mass spectrometry. A total of 5,417 antral follicle proteins were identified in the three groups, of which 194 were differentially abundant between the vehicle and PHT Mix 32 group, and 136 between the vehicle and PHT Mix 500 group. Gene ontology analysis revealed that the two treatments of the phthalate mixture upregulate and downregulate distinctive processes, supporting non-monotonic effects of phthalates on the antral follicle proteome. Taken together, these results reveal that a human relevant mixture of DBP, BBP, and DEHP alters the antral follicle proteome and merits further evaluation to elucidate the molecular mechanisms by which phthalates cause negative reproductive outcomes.
2024-07-18 | PXD047061 | Pride
Project description:The dormant population of ovarian primordial follicles is determined at birth and serves as the reservoir for future female fertility. Of equal importance to fertility is the rate that primordial follicles activate and enter folliculogenesis, yet our understanding of the molecular, biochemical, and cellular processes underpinning primordial follicle activation remains limited. The survival of primordial follicles relies on the correct complement and morphology of granulosa cells, which provide signalling factors essential for oocyte and follicular survival. To investigate the contribution of granulosa cells in the primordial-to-primary follicle transition, ovaries from C57Bl/6 mice were enzymatically dissociated at two time points spanning the initial wave of primordial follicle activation. Post-natal day (PND) 1 ovaries yielded primordial granulosa cells, and PND4 ovaries yielded a mixed population of both primordial and primary granulosa cells. The comparative transcriptome of granulosa cells at these time points was generated via the Illumina NextSeq 500 system which identified 132 significantly differentially expressed transcripts. This transcriptomic dataset confirmed the expression of factors known to be involved in primordial follicle activation belonging to TGF-B and EIF4E signalling pathways, as well as novel factors linked to pathways involved in primordial follicle activation (ZFX, POD1, FRZB). This study highlights the dynamic changes in gene expression of granulosa cells during primordial follicle activation and provides evidence for a renewed focus into the Wnt signalling pathway’s role in primordial follicle activation.
2020-12-10 | GSE162927 | GEO
Project description:The assembly of the developmentally arrested primordial follicle and subsequent transition to the primary follicle are poorly understood processes critical to ovarian biology. Abnormal primordial follicle development can lead to pathologies such as premature ovarian failure. The current study used a genome-wide expression profile to investigate primordial follicle assembly and development. Rat ovaries with predominantly unassembled, primordial, or primary follicles were obtained. RNA from these ovaries was hybridized to rat microarray gene chips, and the gene expression (i.e., ovarian transcriptome) was compared between the developmental stages. Analysis of the ovarian transcriptome demonstrated 148 genes up-regulated and 50 genes down-regulated between the unassembled and primordial follicle stages. Observations demonstrate 80 genes up-regulated and 44 genes down-regulated between the primordial and primary follicle stages. The analysis demonstrated 2332 genes common among the three developmental stages, 146 genes specific for the unassembled follicles, 94 genes specific for the primordial follicles, and 151 genes specific for the primary follicles. Steroidogenic genes are up-regulated between unassembled and primordial follicles, and then many are again down-regulated between primordial and primary follicles. The hormones inhibin and Mullerian inhibitory substance (MIS) display a similar pattern of expression with the highest levels of mRNA in the primordial follicles. Several novel unknown genes that had dramatic changes in expression during primordial follicle development were also identified. Gene families/clusters identified that were up-regulated from unassembled to primordial follicles include growth factors and signal transduction gene clusters, whereas a down-regulated gene family was the synaptonemal complex genes associated with meiosis. Gene families/clusters that were up-regulated between primordial and primary follicles included immune response genes, metabolic enzymes, and proteases, whereas down-regulated gene families include the globulin genes and some steroidogenic genes. The expression of several growth factors changed during primordial follicle development, including vascular endothelial growth factor and insulin-like growth factor II. Elucidation of how these changes in gene expression coordinate primordial follicle assembly and the primordial to primary follicle transition provides a better understanding of these critical biological processes and allows selection of candidate regulatory factors for further investigation. Experiment Overall Design: RNA samples from two control groups (pooled untreated cultured ovaries) are compared to two treated groups (pooled cultured ovaries treated with progesterone)
2008-06-16 | E-GEOD-9300 | biostudies-arrayexpress