Reproductive chemical database: a curated database of chemicals that modulate protein targets regulating important reproductive biological processes.

Recent studies have shifted the spotlight from adult disease to gametogenesis and embryo developmental events, and these are greatly affected by various environmental chemicals, such as drugs, metabolites, pollutants, and others. Growing research has highlighted the critical importance of identifying and understanding the roles of chemicals in reproductive biology. However, the functions and mechanisms of chemicals in reproductive processes remain incomplete.

Metformin promotes female germline stem cell proliferation by upregulating Gata-binding protein 2 with histone β-hydroxybutyrylation.

Background: Metformin as a first-line clinical anti-diabetic agent prolongs the lifespan of model animals and promotes cell proliferation. However, the molecular mechanisms underlying the proliferative phenotype, especially in epigenetics, have rarely been reported. The aim of this study was to investigate the physiological effects of metformin on female germline stem cells (FGSCs) in vivo and in vitro, uncover β-hydroxybutyrylation epigenetic modification roles of metformin and identify the mechanism of histone H2B Lys5 β-hydroxybutyrylation (H2BK5bhb) in Gata-binding protein 2 (Gata2)-mediated proliferation promotion of FGSCs.

YTHDF1 phase separation triggers the fate transition of spermatogonial stem cells by activating the IκB-NF-κB-CCND1 axis.

N-methyladenosine (mA) modification controls cell fate determination. Here, we show that liquid-liquid phase separation (LLPS) of YTH N-methyladenosine RNA binding protein 1 (YTHDF1), a pivotal mA "reader" protein, promotes the transdifferentiation of spermatogonial stem cells (SSCs) into neural stem cell-like cells by activating the IκB-nuclear factor κB (NF-κB)-CCND1 axis. The inhibition of IκBα/β mRNA translation mediated by YTHDF1 LLPS is the key to the activation of the IκB-NF-κB-CCND1 axis.

Mechanistic insights into HuR inhibitor MS-444 arresting embryonic development revealed by low-input RNA-seq and STORM.

With improvements in the survival rate of patients with cancer, fertility maintenance has become a major concern in terms of cancer treatment for women of reproductive age. Thus, it is important to examine the impact on fertility of anticancer drugs that are used clinically or are undergoing trials. The HuR small-molecule inhibitor MS-444 has been used in many cancer treatment studies, but its reproductive toxicity in females is unknown.

Three-dimensional genome structure shapes the recombination landscape of chromatin features during female germline stem cell development.

Background: During meiosis of mammalian cells, chromatin undergoes drastic reorganization. However, the dynamics of the three-dimensional (3D) chromatin structure during the development of female germline stem cells (FGSCs) are poorly understood.

Methods: The high-throughput chromosome conformation capture technique was used to probe the 3D structure of chromatin in mouse germ cells at each stage of FGSC development.

Retinoic acid induced meiosis initiation in female germline stem cells by remodelling three-dimensional chromatin structure.

Objectives: This study aimed to clarify the regulation and mechanism of meiotic initiation in FGSC development.

Materials And Methods: FGSCs were induced to differentiate into meiosis in differentiation medium. RNA sequencing was performed to analysis the difference of transcription level.

Regulates the Development of Female Germline Stem Cells by Modulating Chromatin Structure and DNA Methylation.

Female germline stem cells (FGSCs) have the ability to self-renew and differentiate into oocytes. , encoded by a maternal effect gene, plays an important role in oogenesis and early embryonic development. However, its function in FGSCs remains unclear.

Offspring production of haploid spermatid-like cells derived from mouse female germline stem cells with chromatin condensation.

Background: During male meiosis, the Y chromosome can form perfect pairing with the X chromosome. However, it is unclear whether mammalian Female germline stem cells (FGSCs) without a Y chromosome can transdifferentiate into functional haploid spermatid-like cells (SLCs).

Results: We found that spermatogenesis was restarted by transplanting FGSCs into Kit mutant testes.

Integrative analysis of the 3D genome structure reveals that CTCF maintains the properties of mouse female germline stem cells.

The three-dimensional configuration of the genome ensures cell type-specific gene expression profiles by placing genes and regulatory elements in close spatial proximity. Here, we used in situ high-throughput chromosome conformation (in situ Hi-C), RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) to characterize the high-order chromatin structure signature of female germline stem cells (FGSCs) and identify its regulating key factor based on the data-driven of multiple omics data. By comparison with pluripotent stem cells (PSCs), adult stem cells (ASCs), and somatic cells at three major levels of chromatin architecture, A/B compartments, topologically associating domains, and chromatin loops, the chromatin architecture of FGSCs was most similar to that of other ASCs and largely different from that of PSCs and somatic cells.

Offspring production of ovarian organoids derived from spermatogonial stem cells by defined factors with chromatin reorganization.

Introduction: Fate determination of germline stem cells remains poorly understood at the chromatin structure level.

Objectives: Our research hopes to develop successful offspring production of ovarian organoids derived from spermatogonial stem cells (SSCs) by defined factors.

Methods: The offspring production from oocytes transdifferentiated from mouse SSCs with tracking of transplanted SSCs in vivo, single cell whole exome sequencing, and in 3D cell culture reconstitution of the process of oogenesis derived from SSCs.

Spermidine induces cytoprotective autophagy of female germline stem cells in vitro and ameliorates aging caused by oxidative stress through upregulated sequestosome-1/p62 expression.

Background: Autophagy is required for oogenesis and plays a critical role in response to aging caused by oxidative stress. However, there have been no reports on regulation of cytoprotective autophagy in female germline stem cells (FGSCs) in response to aging caused by oxidative stress.

Results: We found that Spermidine (SPD) significantly increased protein expression of autophagy markers microtubule-associated protein 1 light chain 3 beta-II (MAP1LC3B-II/LC3B-II) and sequestosome-1/p62 (SQSTM1/p62), and evoked autophagic flux in FGSCs.

Comparison of RNA mA and DNA methylation profiles between mouse female germline stem cells and STO cells.

N-methyladenosine (mA) methylation modification is the most prevalent and abundant internal modification of eukaryotic mRNAs. Increasing evidence has shown that mRNA mA plays important roles in the development of stem cells. However, to the best of our knowledge, no reports about the roles of mRNA mA in mouse female germline stem cells (mFGSCs) have been published.

Identifying cortical specific long noncoding RNAs modified by mA RNA methylation in mouse brains.

Proper development of the mammalian cerebral cortex relies on precise gene expression regulation. Increasing evidence shows that cortical development is regulated by both mRNAs and long noncoding RNAs (lncRNAs), which also are modified by -methyladenosine (mA). Patterns of mA-methylation in lncRNAs in the developing cortex have not been uncovered.

C28 induced autophagy of female germline stem cells in vitro with changes of H3K27 acetylation and transcriptomics.

There are a few studies indicating that small molecular compounds affect the proliferation, differentiation, apoptosis, and autophagy of female germline stem cells (FGSCs). However, whether small molecular compound 28 (C28) affect development of FGSCs remains unknown. In this study, we found that C28 reduced the viability and proliferation of FGSCs, respectively.

Integrated Glycosylation Patterns of Glycoproteins and DNA Methylation Landscapes in Mammalian Oogenesis and Preimplantation Embryo Development.

Glycosylation is one of the most fundamental post-translational modifications. However, the glycosylation patterns of glycoproteins have not been analyzed in mammalian preimplantation embryos, because of technical difficulties and scarcity of the required materials. Using high-throughput lectin microarrays of low-input cells and electrochemical techniques, an integration analysis of the DNA methylation and glycosylation landscapes of mammal oogenesis and preimplantation embryo development was performed.

Alternative splicing signatures in preimplantation embryo development.

Background: Preimplantation embryo development is a highly ordered sequence of processes and it requires a precise temporal and spatial control of gene expression. Alternative splicing (AS) is a crucial process that changes the genomic instructions into functional proteins, playing a critical role in the regulation of gene expression. Therefore, studies of AS can significantly improve our understanding of transcription and splicing events in preimplantation embryo development.

Expression profiling dataset of competing endogenous RNA in pre-eclampsia.

This data descriptor is an extended version of the methodologies which have been described in a related paper [1]; its purpose is to disseminate the raw data and analyzed data produced in this experiment. For more insight please see the research article, "competing endogenous RNA expression profiling in pre-eclampsia identifies hsa_circ_0036877 as a potential novel blood biomarker for early pre-eclampsia" (Xiaopeng Hu and Junping Ao, 2018) [1]. Using microarray analysis, we investigated competing endogenous RNA (ceRNA) expression profiles in placentas of women with severe pre-eclampsia (SPE) and normal pregnancies.

Comprehensive Transcriptomic Analysis of Mouse Gonadal Development Involving Sexual Differentiation, Meiosis and Gametogenesis.

Background: Mammalian gonadal development is crucial for fertility. Sexual differentiation, meiosis and gametogenesis are critical events in the process of gonadal development. Abnormalities in any of these events may cause infertility.

C89 Induces Autophagy of Female Germline Stem Cells via Inhibition of the PI3K-Akt Pathway In Vitro.

Postnatal female germline stem cells (FGSCs) are a type of germline stem cell with self-renewal ability and the capacity of differentiation toward oocyte. The proliferation, differentiation, and apoptosis of FGSCs have been researched in recent years, but autophagy in FGSCs has not been explored. This study investigated the effects of the small-molecule compound 89 (C89) on FGSCs and the underlying molecular mechanism in vitro.

Genome-wide identification and characterization of long noncoding and circular RNAs in germline stem cells.

Germline stem cells are germ cells at an early developmental stage, so their development is key to ensuring human reproduction. There is increasing evidence that long noncoding RNA (lncRNA) and circular RNA (circRNA) play important roles in the development of germ cells. This data descriptor provides unique lncRNA and circRNA transcriptomic information for mouse germline stem cells.

Long noncoding RNA growth arrest-specific 5 promotes proliferation and survival of female germline stem cells in vitro.

Female germline stem cells (FGSCs) are proposed to be a key factor for ameliorating female infertility. Previously we have shown that neonatal and adult FGSCs could be isolated and purified from mouse ovarian tissues. The long noncoding (lnc) RNA growth arrest-specific 5 sequence (GAS5) transcribed from mammalian genomes plays important regulatory roles in various developmental processes.