Dataset Information

MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis.

ABSTRACT: MicroRNAs (miRNAs) are short, noncoding RNAs that posttranscriptionally regulate gene expression. In the past decade, studies on miRNAs in ovaries have revealed the key roles of miRNAs in ovarian development and function. In this review, we first introduce the development of follicular atresia research and then summarize genome-wide studies on the ovarian miRNA profiles of different mammalian species. Differentially expressed miRNA profiles during atresia and other biological processes are herein compared. In addition, current knowledge on confirmed functional miRNAs during the follicular atresia process, which is mostly indicated by granulosa cell (GC) apoptosis, is presented. The main miRNA families and clusters, including the let-7 family, miR-23-27-24 cluster, miR-183-96-182 cluster and miR-17-92 cluster, and related pathways that are involved in follicular atresia are thoroughly summarized. A deep understanding of the roles of miRNA networks will not only help elucidate the mechanisms of GC apoptosis, follicular development, atresia and their disorders but also offer new diagnostic and treatment strategies for infertility and other ovarian dysfunctions.

SUBMITTER: Zhang J

PROVIDER: S-EPMC6329178 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis.

Zhang Jinbi J Xu Yinxue Y Liu Honglin H Pan Zengxiang Z

Reproductive biology and endocrinology : RB&E 20190110 1

MicroRNAs (miRNAs) are short, noncoding RNAs that posttranscriptionally regulate gene expression. In the past decade, studies on miRNAs in ovaries have revealed the key roles of miRNAs in ovarian development and function. In this review, we first introduce the development of follicular atresia research and then summarize genome-wide studies on the ovarian miRNA profiles of different mammalian species. Differentially expressed miRNA profiles during atresia and other biological processes are herei ...[more]

PMID: 30630485

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Project description:High temperature affects egg quality and increases follicular atresia in teleosts. The present study aimed to explore the regulated mechanism of ovary syndrome of Nile tilapia (Oreochromis niloticus) exposed to heat stress. To this end, we conducted histological and biochemical analyses and integrated miRNA-target gene analyses. The histochemical analyses confirmed that heat stress promoted the apoptosis of granulosa cell and therefore resulted in increased follicular atresia in the ovary. Heat stress led to the differential expression of multiple miRNAs (miR-27e, -27b-3p, -33, -34a -133a-5p, and -301b-5p). In a luciferase activity assay, miR-33 bound to the 3′-untranslated region (UTR) of the TGFβ1I1 (transforming growth factor-β1-induced transcript 1) gene and inhibited its expression. A TGFβ1I1 gene signal was detected in the granulosa cells of Nile tilapia by immunohistochemical analysis. Up-regulation of the miR-33 of tilapia at 6 d and 12 d exposed to heat (34.5 °C ± 0.5 °C) had significant down-regulation of the TGFβ1I1 expression of the gene and protein in tilapia ovaries. An miRNA-target gene integrated analysis revealed that miR-33 and TGFβ1I1 function in an apoptosis-related signal pathway. The signal transduction of the vascular endothelial growth factor (VEGF) family members VEGFA and its receptor (KDR) in the heat-stressed group decreased significantly compared with the control group. Transcript-levels of the Bax and Caspase-3 as apoptotic promotors were activated and Bcl-2 and Caspase-8 as apoptotic inhibitors were suppressed in the heat-stressed tilapia. These results suggest that heat stress increases the expression of miR-33, which targets TGFβ1I1 and inhibits its expression, resulting in decreased levels of follicle-stimulating hormone and 17β-estradiol and increased apoptosis by suppressing VEGF signaling, eventually inducing follicular atresia. In conclusion, our results show that the miR-33/TGFβ1I1 axis of Nile tilapia is involved in the follicular development of broodstock, and can suppress VEGF signaling to accelerate follicular atresia. Our findings demonstrate the suppressive role of miR-33 during oocyte development in Nile tilapia.

Project description:BackgroundThe major function of the ovary is to produce oocytes for fertilisation. Oocytes mature in follicles surrounded by nurturing granulosa cells and all are enclosed by a basal lamina. During growth, granulosa cells replicate and a large fluid-filled cavity (the antrum) develops in the centre. Only follicles that have enlarged to over 10 mm can ovulate in cows. In mammals, the number of primordial follicles far exceeds the numbers that ever ovulate and atresia or regression of follicles is a mechanism to regulate the number of oocytes ovulated and to contribute to the timing of ovulation. To better understand the molecular basis of follicular atresia, we undertook transcriptome profiling of granulosa cells from healthy (n = 10) and atretic (n = 5) bovine follicles at early antral stages (< 5 mm).ResultsPrincipal Component Analysis (PCA) and hierarchical classification of the signal intensity plots for the arrays showed primary clustering into two groups, healthy and atretic. These analyses and size-frequency plots of coefficients of variation of signal intensities revealed that the healthy follicles were more heterogeneous. Examining the differentially-expressed genes the most significantly affected functions in atretic follicles were cell death, organ development, tissue development and embryonic development. The overall processes influenced by transcription factor gene TP53 were predicted to be activated, whereas those of MYC were inhibited on the basis of known interactions with the genes in our dataset. The top ranked canonical pathway contained signalling molecules common to various inflammatory/fibrotic pathways such as the transforming growth factor-β and tumour necrosis factor-α pathways. The two most significant networks also reflect this pattern of tissue remodelling/fibrosis gene expression. These networks also contain molecules which are present in the canonical pathways of hepatic fibrosis/hepatic stellate cell activation and transforming growth factor-β signalling and were up regulated.ConclusionsSmall healthy antral follicles, which have a number of growth outcomes, exhibit greater variability in gene expression, particularly in genes associated with cell division and other growth-related functions. Atresia, on the other hand, not only involves cell death but clearly is an active process similar to wound healing.

Dataset Information

MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis.

Publications

MicroRNAs in ovarian follicular atresia and granulosa cell apoptosis.

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