MicroRNA-202 is a gatekeeper of meiosis initiation and regulates recombination in male germ line
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE126936 | GEO | 2020/02/15
REPOSITORIES: GEO
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Project description:Meiosis is a specialized form of cell division essential for sexual reproduction. The unique cellular events of meiosis have been extensively studied in model eukaryotes, including mammals. In mammals, the molecular and cellular changes that germ cells must undergo to transition from mitotic spermatogonia to meiotic spermatocytes remain largely undefined. Retinoic acid (RA) has been proposed as the meiosis inducing substance (MIS) required for female and male meiotic initiation. However, evidence for this presumption is based on studies of fetal gonads – meiosis is initiated in fetal ovaries but suppressed in fetal testes. Critically, the requirement for RA in meiosis has never been formally tested because germ cell differentiation and meiotic initiation in the fetal ovary are temporally inseparable. Using the postnatal mouse testis, where differentiation and meiotic initiation are temporally distinct (8.6 days apart), we test the hypothesis that RA is dispensable for initiation and progression through meiosis. Complementary in vivo experimental models were designed to address the hypothesis. In the first, “RA-sufficient” (RA-suf) model, spermatogenesis was synchronized by administration of potent and selective RA synthesis inhibitor; as a result, testes contained only undifferentiated spermatogonia. Then, the inhibitor was discontinued, and mice were given a single dose of exogenous RA to initiate spermatogonial differentiation. Germ cells completed differentiation, entered and completed meiosis, and formed haploid gametes at predicted timepoints. In the second, “RA-deficient” (RA-def) model, mice were treated as above, except the inhibitor was administered continuously. The lack of testicular RA in this model was confirmed in multiple ways, including assessment of RA-responsive gene expression, in vitro serum-free cultures, and dose-response experiments. To our surprise, germ cells in RA-def testes completed differentiation, underwent meiotic DNA replication, completed the landmark cytological processes of meiosis, and formed postmeiotic haploid spermatids, all on the predicted timeline of the RA-suf model. To define the effect of RA-deficiency on gene expression during meiotic initiation, large, highly enriched populations of premeiotic spermatogonia from RA-suf mice, and meiotic preleptotene spermatocytes from both models were FACS-isolated and subjected to bulk RNA-seq. Interestingly, analyses revealed few significant differences in expression of characteristic meiotic genes at the mRNA level. However, genes that were significantly different between RA-suf and RA-def preleptotene spermatocytes were associated with spermiogenesis functions. Taken together, our data reveal that, after initiating spermatogonial differentiation, RA is dispensable for initiation, progression through, and completion of meiosis in the male germline.
2023-07-03 | GSE194376 | GEO
Project description:MicroRNA-202 is a gatekeeper of meiosis initiation and regulates recombination in male germ line
| PRJNA523810 | ENA
Project description:Prophase I of male meiosis involves dynamic chromosome segregation processes during early spermatogenesis, including synapsis, meiotic recombination, and cohesion. Genetic defects in genes participating in these processes consistently cause reproduction failure in mice. To identify candidate genes responsible for infertility in humans, we performed expression profiling of mouse spermatogenic cells undergoing meiotic prophase I. Cell fractions enriched in spermatogonia, leptotene/zygotene spermatocytes, or pachytene spermatocytes were separately isolated from mouse testes for RNA extraction. To minimize the contamination of other cell types, we fractionated the testicular cells undergoing the first round of spermatogenesis using Percoll gradient procedure. The cell fractions were characterized by morphological analysis by phase contrast microscopy and Nomarski interference microscopy, and then expression of cell lineage- and spermatogenesis stage-specific genes were examined by RT-PCR. The most enriched fractions for spermatogonia (fraction2 from day8), leptotene/zygotene spermatocytes (fraction5 from day12), and pachytene spermatocytes (fraction8 from day15) were subjected to hybridization on Affymetrix microarrays.
2010-03-31 | E-GEOD-19532 | biostudies-arrayexpress
Project description:As a serine/threonine phosphatase, protein phosphatase 2A (PP2A) is essential in numerous physiological processes. Our previously study confirmed PP2A dysfunction can cause azoospermia by generating catalytic subunit of PP2A (Ppp2ca) conditional knockout (CKO) in C57BL/6J mice. Here, we further explored the possible mechanisms by focusing on meiosis initiation and spermatogenesis. The deficiency of Ppp2ca in germ cells conspicuously disturbed spermatogonial differentiation and lead to pachytene arrest, accompanied by defects in programmed double-strand break (DSB) repair and meiotic sex chromosome inactivation (MSCI). Furthermore, Ppp2ca-deficient spermatocytes exhibited abnormal agglutination and cohesion complex degradation of chromosome, probably contributing to pachytene arrest. Our study demonstrates the irreplaceable role of PP2A in spermatogenesis and provide more evidences on azoospermia etiology.
2021-12-01 | GSE181132 | GEO
Project description:We report bulk RNA-sequencing data for undifferentiated and defined subpopulations of differentiating murine spermatogonia. We have sequenced two replicates each of wild-type and STRA8 knock-out sets of spermatogonia to assess transcriptional changes that occur throughout spermatogonial development prior to meiotic entry.
2020-07-29 | GSE155307 | GEO
Project description:Active enhancers are identified by H3K27ac ChIP-seq analysis. To determine the dynamics of active enhancers during spermatogenesis, we performed H3K27ac ChIP-seq and detected reagions of active enhancers during spermatogenesis. We analyzed four representative stages of spermatogenesis: Thy1+ undifferentiated spermatogonia, which contains spermatogonial stem cells and progenitor cells; c-Kit+ differentiating spermatogonia from P7 testes; purified pachytene spermatocytes (PS) undergoing meiosis; and postmeiotic round spermatids (RS) from adult testes.
2020-05-02 | GSE130652 | GEO
Project description:To determine the dynamics of open chromatin at a genomic resolution during spermatogenesis, we performed ATAC-seq and detected genomic regions of accessible chromatin by Tn5 transposase during spermatogenesis. We analyzed four representative stages of spermatogenesis: Thy1+ undifferentiated spermatogonia, which contains spermatogonial stem cells and progenitor cells; c-Kit+ differentiating spermatogonia from P7 testes; purified pachytene spermatocytes (PS) undergoing meiosis; and postmeiotic round spermatids (RS) from adult testes
2017-10-18 | GSE102954 | GEO
Project description:Spermatogenesis is dependent primarily on testosterone action on the Sertoli cells. Although the identification of testosterone-regulated target genes in Sertoli cells has been approached using microarray analysis to compare gene expression in mice with androgen receptor (AR) elimination in the Sertoli cells (SCARKO) and wild type mice, the analysis has been complicated by alteration of germ cell composition of the testis when pubertal or adult mice were used and differences in Sertoli-cell gene expression from those in adult when prepubertal mice were used. Since the testicular cell components of adult jsd (Utp14bjsd ,juvenile spermatogonial depletion) mice and SCARKO-jsd mice are essentially identical, consisting of only type A spermatogonia and somatic cells, comparisons of gene expression profiles between jsd and SCARKO-jsd testes would identify AR regulated genes in adult Sertoli cells, with minimum effects of cell number changes. Microarray analysis identified 161 genes as downregulated and 202 genes as upregulated in the SCARKO-jsd mice compared to jsd mice. Some of the genes identified in the previous studies, including Rhox5, Drd4, and Fhod3, were also AR-regulated in the jsd testes but others, such as proteases and components of junctional complexes, were not androgen regulated in our model. Surprisingly, a set of germ-cell-specific genes preferentially expressed in differentiated spermatogonia and meiotic cells, including Meig1, Sycp3, and Ddx4, were all upregulated about 2-fold in SCARKO-jsd testes, demonstrating that, although there was no significant differentiation to spermatocytes in SCARKO-jsd mice, AR-regulated genes in Sertoli cells are involved in the regulation of spermatogonial differentiation. Further gene ontogeny analysis revealed possible sets of genes whose expression changes may be involved in the disruption of Sertoli cell organization in SCARKO-jsd testes. Comparisons of gene expression profiles between the testis of jsd mice (n=3) and SCARKO-jsd mice (n=3).
2010-09-06 | E-GEOD-20918 | biostudies-arrayexpress
Project description:Monopolar spindle 1 (Mps1), which plays a critical role in somatic mitosis, has also been revealed to be essential for meiosis I in oocytes. Spermatogenesis is an important process involving successive mitosis and meiosis, but the function of Mps1 in spermatogenesis remains unclear. Here, we generated Mps1 conditional knockout mice and found that Ddx4-cre-driven loss of Mps1 in male mice resulted in depletion of undifferentiated spermatogonial cells and subsequently of differentiated spermatogonia and spermatocytes. In addition, Stra8-cre-driven ablation of Mps1 in male mice led to germ cell loss and fertility reduction. Spermatocytes lacking Mps1 were blocked at the zygotene-to-pachytene transition in prophase of meiosis I, and the expression of many meiotic genes was decreased, while that of apoptotic genes was increased. Moreover, we also detected increased apoptosis in spermatocytes with Mps1 knockout, which may have been the reason why germ cells were lost. Taken together, our findings indicate that Mps1 is required for mitosis of gonocytes and spermatogonia, differentiation of undifferentiated spermatogonia, and progression of meiosis I in spermatocytes.
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Project description:To reveal distinct transcriptomes associated with various spermatogenic cells, including spermatogonial stem cells and all of their subsequent progeny, single-cell transcriptomes from Adult human spermatogonia, StaPut-enriched spermatocytes and spermatids, or unselected steady-state spermatogenic cells were used for Drop-Seq analysis. We used the 10x Genomics Chromium (Drop-Seq) to perform single-cell RNA-seq
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