scholarly journals Disorganization of the germ cell pool leads to primary ovarian insufficiency

Reproduction ◽  
2017 ◽  
Vol 153 (6) ◽  
pp. R205-R213 ◽  
Author(s):  
Ikko Kawashima ◽  
Kazuhiro Kawamura
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
Embryonic Stem ◽  
Primordial Follicle ◽  
Cell Development ◽  
Primary Ovarian Insufficiency ◽  
Ovarian Insufficiency ◽  
Germ Cell Development ◽  
Female Germ Cell

The mammalian ovary is an organ that controls female germ cell development, storing them and releasing mature oocytes for transporting to the oviduct. During the fetal stage, female germ cells change from a proliferative state to meiosis before forming follicles with the potential for the growth of surrounding somatic cells. Understanding of molecular and physiological bases of germ cell development in the fetal ovary contributed not only to the elucidation of genetic disorders in primary ovarian insufficiency (POI), but also to the advancement of novel treatments for patients with POI. Accumulating evidence indicates that mutations inNOBOX,DAZLandFIGLAgenes are associated with POI. In addition, cell biology studies revealed the important roles of these genes as essential translational factors for germ cell development. Recent insights into the role of the PI3K (phosphatidylinositol 3-kinase)-Akt signaling pathway in primordial follicle activation allowed the development of a new infertility treatment, IVA (in vitroactivation), leading to successful pregnancy/delivery in POI patients. Furthermore, elucidation of genetic dynamics underlying female germ cell development could allow regeneration of oocytes from ES (embryonic stem)/iPS (induced pluripotent stem) cells in mammals. The purpose of this review is to summarize basic findings related to female germ cell development and potential clinical implications, especially focusing on POI etiologies. We also summarize evolving new POI therapies based on IVA as well as oocyte regeneration.

scholarly journals Survival Motor Neuron Protein Participates in Mouse Germ Cell Development and Spermatogonium Maintenance

2020 ◽  
Vol 21 (3) ◽  
pp. 794 ◽  
Author(s):  
Wei-Fang Chang ◽  
Jie Xu ◽  
Tzu-Ying Lin ◽  
Jing Hsu ◽  
Hsiu-Mei Hsieh-Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Motor Neuron ◽  
Cell Biology ◽  
Critical Role ◽  
Embryonic Stem ◽  
Cell Development ◽  
Survival Motor Neuron ◽  
Specific Marker ◽  
Germ Cell Development

The defective human survival motor neuron 1 (SMN1) gene leads to spinal muscular atrophy (SMA), the most common genetic cause of infant mortality. We previously reported that loss of SMN results in rapid differentiation of Drosophila germline stem cells and mouse embryonic stem cells (ESCs), indicating that SMN also plays important roles in germ cell development and stem cell biology. Here, we show that in healthy mice, SMN is highly expressed in the gonadal tissues, prepubertal spermatogonia, and adult spermatocytes, whereas low SMN expression is found in differentiated spermatid and sperm. In SMA-like mice, the growth of testis tissues is retarded, accompanied with gamete development abnormalities and loss of the spermatogonia-specific marker. Consistently, knockdown of Smn1 in spermatogonial stem cells (SSCs) leads to a compromised regeneration capacity in vitro and in vivo in transplantation experiments. In SMA-like mice, apoptosis and accumulation of the R-loop structure were significantly elevated, indicating that SMN plays a critical role in the survival of male germ cells. The present work demonstrates that SMN, in addition to its critical roles in neuronal development, participates in mouse germ cell and spermatogonium maintenance.

In vitro reconstitution of germ cell development†

2019 ◽  
Vol 101 (3) ◽  
pp. 567-578 ◽  
Author(s):  
Katsuhiko Hayashi
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
New Technology ◽  
Rapid Development ◽  
Cell Development ◽  
Alternative Source ◽  
Germ Cell Development ◽  
In Vitro Reconstitution ◽  
Key Issues

Abstract Germ cell development is a series of highly specialized processes through which diploid pluripotent cells differentiate into haploid gametes. The processes include biologically important events such as epigenetic reprogramming, sex determination, and meiosis. The mechanisms underlying these events are key issues in reproductive and developmental biology, yet they still remain elusive. As a tool to elucidate these mechanisms, in vitro gametogenesis, which reproduces germ cell development in culture, has long been sought for decades. Recently, methods of in vitro gametogenesis have undergone rapid development in association with stem cell biology, opening many possibilities in this field. This new technology is considered an alternative source of gametes for the reproduction of animals and perhaps humans. This review summarizes current advances and problems in in vitro gametogenesis.

Induction of the germ cell fate from pluripotent stem cells in cynomolgus monkeys†

2019 ◽  
Vol 102 (3) ◽  
pp. 620-638 ◽  
Author(s):  
Yoshitake Sakai ◽  
Tomonori Nakamura ◽  
Ikuhiro Okamoto ◽  
Sayuri Gyobu-Motani ◽  
Hiroshi Ohta ◽  
...  
Keyword(s):  
Stem Cells ◽  
Germ Cell ◽  
Cell Fate ◽  
Pluripotent Stem Cells ◽  
Primordial Germ Cell ◽  
Embryonic Stem ◽  
Cell Development ◽  
Cynomolgus Monkeys ◽  
Germ Cell Development

Abstract In vitro reconstitution of germ-cell development from pluripotent stem cells (PSCs) has created key opportunities to explore the fundamental mechanisms underlying germ-cell development, particularly in mice and humans. Importantly, such investigations have clarified critical species differences in the mechanisms regulating mouse and human germ-cell development, highlighting the necessity of establishing an in vitro germ-cell development system in other mammals, such as non-human primates. Here, we show that multiple lines of embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) in cynomolgus monkeys (Macaca fascicularis; cy) can be maintained stably in an undifferentiated state under a defined condition with an inhibitor for WNT signaling, and such PSCs are induced efficiently into primordial germ cell-like cells (PGCLCs) bearing a transcriptome similar to early cyPGCs. Interestingly, the induction kinetics of cyPGCLCs from cyPSCs is faster than that of human (h) PGCLCs from hPSCs, and while the transcriptome dynamics during cyPGCLC induction is relatively similar to that during hPGCLC induction, it is substantially divergent from that during mouse (m) PGCLC induction. Our findings delineate common as well as species-specific traits for PGC specification, creating a foundation for parallel investigations into the mechanism for germ-cell development in mice, monkeys, and humans.

scholarly journals In vitro post-meiotic germ cell development from human embryonic stem cells

2009 ◽  
Vol 24 (12) ◽  
pp. 3150-3159 ◽  
Author(s):  
B. Aflatoonian ◽  
L. Ruban ◽  
M. Jones ◽  
R. Aflatoonian ◽  
A. Fazeli ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Germ Cell ◽  
Human Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Cell Development ◽  
Germ Cell Development

Dynamic changes in the subnuclear organisation of pre-mRNA splicing proteins and RBM during human germ cell development

1998 ◽  
Vol 111 (9) ◽  
pp. 1255-1265 ◽  
Author(s):  
D.J. Elliott ◽  
K. Oghene ◽  
G. Makarov ◽  
O. Makarova ◽  
T.B. Hargreave ◽  
...  
Keyword(s):  
Germ Cell ◽  
Cell Biology ◽  
Rna Binding ◽  
Spatial Association ◽  
Cell Types ◽  
Cell Development ◽  
Mrna Splicing ◽  
Human Testis ◽  
Germ Cell Development ◽  
Nuclear Regions

RBM is a germ-cell-specific RNA-binding protein encoded by the Y chromosome in all mammals, implying an important and evolutionarily conserved (but as yet unidentified) function during male germ cell development. In order to address this function, we have developed new antibody reagents to immunolocalise RBM in the different cell types in the human testis. We find that RBM has a different expression profile from its closest homologue hnRNPG. Despite its ubiquitous expression in all transcriptionally active germ cell types, RBM has a complex and dynamic cell biology in human germ cells. The ratio of RBM distributed between punctate nuclear structures and the remainder of the nucleoplasm is dynamically modulated over the course of germ cell development. Moreover, pre-mRNA splicing components are targeted to the same punctate nuclear regions as RBM during the early stages of germ cell development but late in meiosis this spatial association breaks down. After meiosis, pre-mRNA splicing components are differentially targeted to a specific region of the nucleus. While pre-mRNA splicing components undergo profound spatial reorganisations during spermatogenesis, neither heterogeneous ribonucleoproteins nor the transcription factor Sp1 show either developmental spatial reorganisations or any specific co-localisation with RBM. These results suggest dynamic and possibly multiple functions for RBM in germ cell development.

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