Primordial germ cell

The mammalian genome undergoes two global epigenetic reprogramming events during the establishment of primordial germ cells and in the pre-implantation embryo after fertilization. These events involve the erasure and re-establishment of DNA methylation marks. However, imprinted genes and transposable elements (TEs) maintain their DNA methylation signatures to ensure normal embryonic development and genome stability. Despite extensive research in mice and humans, there is limited knowledge regarding environmentally induced epigenetic marks that escape epigenetic reprogramming in other species...

Premature ovarian insufficiency (POI) is a common reproductive aging disorder due to a dramatic decline of ovarian function before 40 years of age. Accumulating evidence reveals that genetic defects, particularly those related to DNA damage response, are a crucial contributing factor to POI. We have demonstrated that the functional Fanconi anemia (FA) pathway maintains the rapid proliferation of primordial germ cells to establish a sufficient reproductive reserve by counteracting replication stress, but the clinical implications of this function in human ovarian function remain to be established...

BACKGROUND: Recapitulating mammalian cell type differentiation in vitro promises to improve our understanding of how these processes happen in vivo, while bringing additional prospects for biomedical applications. The establishment of stem cell-derived embryo models and embryonic organoids, which have experienced explosive growth over the last few years, open new avenues for research due to their scale, reproducibility, and accessibility. Embryo models mimic various developmental stages, exhibit different degrees of complexity, and can be established across species...

Maternal exposures during pregnancy can impact the establishment of the ovarian reserve in offspring, the lifetime supply of germ cells that determine a woman's reproductive lifespan. However, despite alcohol consumption being common in women of reproductive age, the impact of prenatal alcohol on ovarian development is rarely investigated. This study used an established rat model of periconceptional ethanol exposure (PCEtOH; 12.5% v / v ethanol) for 4 days prior to 4 days post-conception. Ovaries were collected from neonates (day 3 and day 10), and genes with protein products involved in regulating the ovarian reserve analyzed by qPCR...

Gametogenesis is the process through which germ cells differentiate into sexually dimorphic gametes, eggs and sperm. In the teleost fish medaka (Oryzias latipes), a germ cell-intrinsic sex determinant, foxl3, triggers germline feminization by activating two genetic pathways that regulate folliculogenesis and meiosis. Here, we identified a pathway involving a dome-shaped microtubule structure that may be the basis of oocyte polarity. This structure was first established in primordial germ cells in both sexes, but was maintained only during oogenesis and was destabilized in differentiating spermatogonia under the influence of Sertoli cells expressing dmrt1...

Both ovarian and testicular germ cell tumors (GCTs) arise from the primordial germ cell and share many similarities. Both malignancies affect mainly young patients, show remarkable responsiveness to cisplatin-based therapy, and have an excellent prognosis, which also highlights the importance of minimizing long-term side effects. However, certain differences can be noted: The spreading of the disease differs, and the staging system and treatment recommendations are dissimilar. Moreover, the prognosis for ovarian GCTs is significantly inferior to that for testicular cancer, as exemplified in this review comparing the survival in Swedish patients diagnosed with testicular (1995-2022) and ovarian (1990-2018) GCTs...

Certain environmental factors can impact fertility and reproductive parameters such as the number and quality of sperm and eggs. One possible mechanism is the perturbation of epigenetic landscapes in the germline. To explore this possibility, we conducted a CRISPRi screen of epigenetic-related genes to identify those that specifically perturb the differentiation of embryonic stem cells (ESCs) into primordial germ cell-like cells (PGCLCs), exploiting a highly scalable cytokine-free platform. Of the 701 genes screened, inhibition of 53 decreased the efficiency of PGCLC formation...

Multiple theories exist to explain cancer initiation, although a consensus on this is crucial for developing effective therapies. 'Somatic mutation theory' suggests that mutations in somatic cells during DNA repair initiates cancer but this concept has several attached paradoxes. Research efforts to identify quiescent cancer stem cells (CSCs) that survive therapy and result in metastasis and recurrence have remained futile. In solid cancers, CSCs are suggested to appear during epithelial-mesenchymal transition by the dedifferentiation and reprogramming of epithelial cells...

Meiosis is a specialized type of cell division that occurs physiologically only in germ cells. We previously demonstrated that MYC-associated factor X (MAX) blocks the ectopic onset of meiosis in embryonic and germline stem cells in culture systems. Here, we investigated the Max gene's role in mouse primordial germ cells. Although Max is generally ubiquitously expressed, we revealed that sexually undifferentiated male and female germ cells had abundant MAX protein because of their higher Max gene expression than somatic cells...

Introduction: Retention of source cell-type epigenetic memory may mitigate the potential for induced pluripotent stem cells (iPSCs) to fully achieve transitions in cell fate in vitro . While this may not preclude the use of iPSC-derived somatic cell types for therapeutic applications, it becomes a major concern impacting the potential use of iPSC-derived germline cell types for reproductive applications. The transition from a source somatic cell type to iPSCs and then on to germ-cell like cells (GCLCs) recapitulates two major epigenetic reprogramming events that normally occur during development in vivo -embryonic reprogramming in the epiblast and germline reprogramming in primordial germ cells (PGCs)...

Primordial germ cells (PGC) are pivotal for gonadal development and reproductive success. Though artificial induction of sterility by targeting PGC are gaining popularity due to its advantages in fish surrogacy and biodiversity management, it is often skill and time intensive. In this study, we have focused on understanding the role of PGCs and the chemotactic SDF-1/CXCR4 signaling on gonad development of Japanese anchovy (JA, Engraulis japonicus), an upcoming marine model organism with eco-commercial values, with an aim to develop a novel, easy, and versatile gonad sterilization method...

The Infinium BeadChip is the most widely used DNA methylome assay technology for population-scale epigenome profiling. However, the standard workflow requires over 200 ng of input DNA, hindering its application to small cell-number samples, such as primordial germ cells. We developed experimental and analysis workflows to extend this technology to suboptimal input DNA conditions, including ultra-low input down to single cells. DNA preamplification significantly enhanced detection rates to over 50% in five-cell samples and ∼25% in single cells...

Primordial germ cells (PGCs) are the founder cells of the germline. The ability to generate PGC-like cells (PGCLCs) from pluripotent stem cells has advanced our knowledge of gametogenesis and holds promise for developing infertility treatments. However, generating an ample supply of PGCLCs for demanding applications such as high-throughput genetic screens has been a limitation. Here, we demonstrated that simultaneous overexpressing 4 transcriptional factors - Nanog and three PGC master regulators Prdm1 , Prdm14 and Tfap2c - in suspended mouse epiblast like cells (EpiLCs) and formative embryonic stem cells (ESCs) results in efficient and cost-effective production of PGCLCs...

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model...

The number of embryonic primordial germ cells in Drosophila is determined by the quantity of germ plasm, whose assembly starts in the posterior region of the oocyte during oogenesis. Here, we report that extending JAK-STAT activity in the posterior somatic follicular epithelium leads to an excess of primordial germ cells in the future embryo. We show that JAK-STAT signaling is necessary for the differentiation of approximately 20 specialized follicle cells maintaining tight contact with the oocyte. These cells define, in the underlying posterior oocyte cortex, the anchoring of the germ cell determinant oskar mRNA...

SDF-1/CXCR4 chemokine signaling are indispensable for cell migration, especially the Primordial Germ Cell (PGC) migration towards the gonadal ridge during early development. We earlier found that this signaling is largely conserved in the Japanese anchovy ( Engraulis japonicus , EJ), and a mere treatment of CXCR4 antagonist, AMD3100, leads to germ cell depletion and thereafter gonad sterilization. However, the effect of AMD3100 was limited. So, in this research, we scouted for CXCR4 antagonist with higher potency by employing advanced artificial intelligence deep learning-based computer simulations...

Bloom (BLM) helicase plays an important role in DNA replication and the maintenance of genome integrity. BLM protein deficiency, which plays a vital role in the sperm-egg union and germ-cell development during reproduction, can lead to severe DNA damage in goats. However, the effect of BLM protein deficiency on goat litter size has not been reported. Herein, we studied the association between the genetic variation in the BLM gene and the number of kids per litter in Guizhou white goats. We explored differences in the expression of the BLM protein in the follicles of single and multi-kid nanny goats...

Primordial germ cells (PGCs) are the earliest precursors of the gametes. During normal development, PGCs only give rise to oocytes or spermatozoa. However, PGCs can acquire pluripotency in vitro by forming embryonic germ (EG) cells and in vivo during teratocarcinogenesis. Classic embryological experiments directly assessed the potency of PGCs by injection into the pre-implantation embryo. As no contribution to embryos or adult mice was observed, PGCs have been described as unipotent. Here, we demonstrate that PGCs injected into 8-cell embryos can initially survive, divide, and contribute to the developing inner cell mass...

The induction of the germ cell lineage from pluripotent stem cells (in vitro gametogenesis) will help understand the mechanisms underlying germ cell differentiation and provide an alternative source of gametes for reproduction. This technology is especially important for cattle, which are among the most important livestock species for milk and meat production. Here, we developed a new method for robust induction of primordial germ cell-like cells (PGCLCs) from newly established bovine embryonic stem (bES) cells...

In vitro induction of primordial germ cell like-cells (PGCLCs) from pluripotent stem cells (PSCs) is a robust method that will contribute to understanding the fundamentals of cell fate decisions, animal breeding, and future reproductive medicine. Here, we introduce this system established in the rat model. We describe a stepwise protocol to induce epiblast-like cells and subsequent PGCLCs by forming spherical aggregates from rat PSCs. We also describe a protocol to mature these PGCLCs from specified/migratory to the gonadal stage by aggregation with female gonadal somatic cells...