scholarly journals Intercellular bridges coordinate the transition from pluripotency to meiosis in mouse fetal oocytes

2021 ◽  
Vol 7 (15) ◽  
pp. eabc6747
Author(s):  
B. Soygur ◽  
R. G. Jaszczak ◽  
A. Fries ◽  
D. H. Nguyen ◽  
S. Malki ◽  
...  

Meiosis is critical to generating oocytes and ensuring female fertility; however, the mechanisms regulating the switch from mitotic primordial germ cells to meiotic germ cells are poorly understood. Here, we implicate intercellular bridges (ICBs) in this state transition. We used three-dimensional in toto imaging to map meiotic initiation in the mouse fetal ovary and revealed a radial geometry of this transition that precedes the established anterior-posterior wave. Our studies reveal that appropriate timing of meiotic entry across the ovary and coordination of mitotic-meiotic transition within a cyst depend on the ICB component Tex14, which we show is required for functional cytoplasmic sharing. We find that Tex14 mutants more rapidly attenuate the pluripotency transcript Dppa3 upon meiotic initiation, and Dppa3 mutants undergo premature meiosis similar to Tex14. Together, these results lead to a model that ICBs coordinate and buffer the transition from pluripotency to meiosis through dilution of regulatory factors.


Reproduction ◽  
2012 ◽  
Vol 144 (5) ◽  
pp. 583-593 ◽  
Author(s):  
F J Stansfield ◽  
J O Nöthling ◽  
J T Soley ◽  
W R Allen

The follicular reserve and its ontogeny in the elephant are of interest because elephants have the longest reproductive life of all land-based mammals. They also have the longest recorded pregnancy, which allows a protracted view of the series of significant events involved in the development of the embryonic and fetal gonads. The large elephant population of Zimbabwe provided the opportunity to collect conceptuses from elephants culled for management reasons and hunted professionally. Five embryos aged 76–96 days and the ovaries of four fetuses aged 4.8–11.2 months were fixed in 4% buffered formalin and studied by conventional histological sectioning and a stereological protocol to calculate the follicle reserve of each fetus. These observations enabled the conclusion that the migration of primordial germ cells into the indifferent gonad terminates at around 76 days of gestation while entry of oogonia into meiosis along with first follicle formation starts at around 5 months. Peak numbers of follicles are present by mid-gestation towards the end of the 6-month mitotic–meiotic transition period. It appears that the cortex of the elephant fetal ovary at mid-gestation (11 months) has already reached a developmental stage exhibited by the ovaries of many other mammals at full term.



PLoS ONE ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. e0200515 ◽  
Author(s):  
Yi-Chen Chen ◽  
Wei-Che Chang ◽  
Shau-Ping Lin ◽  
Masataka Minami ◽  
Christian Jean ◽  
...  


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2422
Author(s):  
Dragos Scarlet ◽  
Stephan Handschuh ◽  
Ursula Reichart ◽  
Giorgia Podico ◽  
Robyn E. Ellerbrock ◽  
...  

It was the aim of this study to characterize the development of the gonads and genital ducts in the equine fetus around the time of sexual differentiation. This included the identification and localization of the primordial germ cell population. Equine fetuses between 45 and 60 days of gestation were evaluated using a combination of micro-computed tomography scanning, immunohistochemistry, and multiplex immunofluorescence. Fetal gonads increased in size 23-fold from 45 to 60 days of gestation, and an even greater increase was observed in the metanephros volume. Signs of mesonephros atrophy were detected during this time. Tubular structures of the fetal testes were present from day 50 onwards, whereas cell clusters dominated in the fetal ovary. The genital ducts were well-differentiated and presented a lumen in all samples. No sign of mesonephric or paramesonephric duct degeneration was detected. Expression of AMH was strong in the fetal testes but absent in ovaries. Irrespective of sex, primordial germ cells selectively expressed LIN28. Migration of primordial germ cells from the mesonephros to the gonad was detected at 45 days, but not at 60 days of development. Their number and distribution within the gonad were influenced (p < 0.05) by fetal sex. Most primordial germ cells (86.8 ± 3.2% in females and 84.6 ± 4.7% in males) were characterized as pluripotent according to co-localization with CD117. However, only a very small percentage of primordial germ cells were proliferating (7.5 ± 1.7% in females and 3.2 ± 1.2% in males) based on co-localization with Ki67. It can be concluded that gonadal sexual differentiation in the horse occurs asynchronously with regard to sex but already before 45 days of gestation.



Reproduction ◽  
2020 ◽  
Author(s):  
Delia Alba Soto ◽  
Pablo Juan Ross

The germ cell lineage ensures the creation of new individuals and perpetuates the genetic information across generations. Primordial germ cells are pioneers of gametes and exist transiently during development until they differentiate into oogonia in females, or spermatogonia in males. Little is known about the molecular characteristics of primordial germ cells in cattle. By performing single-cell RNA-sequencing, quantitative real-time PCR, and immunofluorescence analyses of fetal gonads between 40 and 90 days of fetal age, we evaluated the molecular signatures of bovine germ cells at the initial stages of gonadal development. Our results indicate that at 50 days of fetal age, bovine primordial germ cells were in the early stages of development, expressing genes of early primordial germ cells, including transcriptional regulators of human germline specification (e.g. SOX17, TFAP2C, and PRDM1). Bovine and human primordial germ cells also share expression of KIT, EPCAM, ITGA6, and PDPN genes coding for membrane-bound proteins, and an asynchronous pattern of differentiation. Additionally, the expression of members of Notch, Nodal/Activin, and BMP signaling cascades in the bovine fetal ovary, suggests that these pathways are involved in the interaction between germ cells and their niche. Results of this study provide insights into the mechanisms involved in the development of bovine primordial germ cells and put in evidence similarities between the bovine and human germline.



Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 775 ◽  
Author(s):  
Tsutomu Endo ◽  
Maria M. Mikedis ◽  
Peter K. Nicholls ◽  
David C. Page ◽  
Dirk G. de Rooij

Retinoic acid (RA), a derivative of vitamin A, is critical for the production of oocytes and sperm in mammals. These gametes derive from primordial germ cells, which colonize the nascent gonad, and later undertake sexual differentiation to produce oocytes or sperm. During fetal development, germ cells in the ovary initiate meiosis in response to RA, whereas those in the testis do not yet initiate meiosis, as they are insulated from RA, and undergo cell cycle arrest. After birth, male germ cells resume proliferation and undergo a transition to spermatogonia, which are destined to develop into haploid spermatozoa via spermatogenesis. Recent findings indicate that RA levels change periodically in adult testes to direct not only meiotic initiation, but also other key developmental transitions to ensure that spermatogenesis is precisely organized for the prodigious output of sperm. This review focuses on how female and male germ cells develop in the ovary and testis, respectively, and the role of RA in this process.



Author(s):  
Dragos Scarlet ◽  
Stephan Handschuh ◽  
Ursula Reichart ◽  
Giorgia Podico ◽  
Robyn E Ellerbrock ◽  
...  

It was the aim of this study to provide a more precise timeframe of development of the gonads and genital ducts in the equine fetus around the time of sexual differentiation. This included the identification and localisation of the primordial germ cell population. Equine fetuses between 45 and 60 days of gestation were evaluated using a combination of micro-computed tomography scanning, immunohistochemistry, and multiplex immunofluorescence. Fetal gonads increased in size by 23-fold from 45 to 60 days of gestation, paralleled by a greater increase in metanephros volume. Signs of mesonephros atrophy were detected during this time. Tubular structures of the fetal testes were present from day 50 onwards, whereas cell clusters dominated in the fetal ovary. The genital ducts were well-differentiated and presented a lumen in all samples. No sign of mesonephric or paramesonephric duct degeneration was detected. Expression of AMH was strong in the fetal testes but absent in ovaries. Irrespective of sex, primordial germ cells selectively expressed LIN28. Migration of primordial germ cells from the mesonephros to the gonad was detected at 45 days, but not at 60 days of development. Their number and distribution within the gonad were influenced (p&amp;lt;0.05) by fetal sex. Most primordial germ cells (86.8 &plusmn; 3.2% in females and 84.6 &plusmn; 4.7% in males) were characterized as pluripotent according to co-localization with CD117. However, only a very small percentage of primordial germ cells was proliferating (7.5 &plusmn; 1.7% in females and 3.2 &plusmn; 1.2% in males) based on co-localization with Ki67. It can be concluded that gonadal sexual differentiation in the horse occurs asynchronously with regard to sex but already before 45 days of gestation.



Development ◽  
1994 ◽  
Vol 120 (10) ◽  
pp. 2925-2932 ◽  
Author(s):  
P.P. Tam ◽  
S.X. Zhou ◽  
S.S. Tan

We have determined the timing of the inactivation and reactivation of the X chromosome in the mouse primordial germ cells (PGCs) by monitoring the expression of an X-linked HMG-lacZ reporter gene. PGCs were identified by their distinct alkaline phosphatase activity and they were first localised in the primitive streak and allantoic bud of the 7.5-day gastrulating embryo. Although inactivation of the transgene was found in some PGCs at these sites, at least 85% of the population were still expressing the lacZ gene. This suggests that, although X-inactivation has commenced during gastrulation, the majority of PGCs still possess two active X chromosomes. Transgene activity remained unchanged during the relocation of PGCs to the hindgut endoderm, but decreased abruptly when PGCs left the hindgut and migrated through the mesentery. X-inactivation was completed during the migration of PGCs, but not simultaneously for the whole population. The first wave of PGCs entering the genital ridge at 9.5 days did not immediately re-activate the silent transgene until about 24 hours later. Re-activation of the transgene took place in over 80% of PGCs entering the genital ridge at 10.5-13.5 days p.c., preceding the entry into meiosis. About 90% of the meiotic germ cells in the 14.5-15.5 day fetal ovary expressed the transgene. Similar profiles of transgene activity were observed in PGCs of embryos that have inherited the lacZ transgene from different parents, showing unequivocally that X-inactivation in the germ cell lineage is not related to parental legacy.(ABSTRACT TRUNCATED AT 250 WORDS)



2018 ◽  
Author(s):  
Yi-Chen Chen ◽  
Wei-Che Chang ◽  
Shau-Ping Lin ◽  
Masataka Minami ◽  
Christian Jean ◽  
...  

AbstractScalable production of avian suspension cell exhibits a valuable potential on therapeutic application by producing recombinant protein and as the substrate for virus growth. This study sought to establish a system with chemically defined components for three-dimensional (3D) culture of chicken primordial germ cells (cPGCs), a pluripotent avian cell type. cPGCs were cultured in medium supplemented with the functional polymer FP003. Viscoelasticity was low in this medium, and cPGCs did not sediment,and consequently their expansion was improved. The total number of cPGCs increased by 17-fold after 1week of culture in 3D-FAot medium, an aseric chemically defined medium containing FP003, indicating that this medium enhances the expansion of cPGCs. Moreover, cPGC cell lines stably expressed the germline-specific reporter VASA:tdTOMATO, as well as other markers of cPGCs, for more than 1 month upon culture in 3D-FAot medium, indicating that the characteristics of these cells are maintained. cPGCs harboring both PGK:EGFP and VASA:tdTOMATO robustly expressed both fluorescent proteins upon culture in 3D-FAot, suggesting that this approach is perspective for recombinant protein production. In summary,this novel 3D culture system can be used to efficiently expand cPGCs in suspension without mechanical stirring or loss of cellular properties. This system provides a platform for large-scale culture ofcPGCs in industry.



Author(s):  
J. R. Ruby ◽  
R. F. Dyer ◽  
R. G. Skalko ◽  
R. F. Gasser ◽  
E. P. Volpe

An electron microscope examination of fetal ovaries has revealed that developing germ cells are connected by intercellular bridges. In this investigation several species have been studied including human, mouse, chicken, and tadpole (Rana pipiens). These studies demonstrate that intercellular connections are similar in morphology regardless of the species.Basically, all bridges are characterized by a band of electron-dense material on the cytoplasmic side of the tri-laminar membrane surrounding the connection (Fig.l). This membrane is continuous with the plasma membrane of the conjoined cells. The dense material, however, never extends beyond the limits of the bridge. Variations in the configuration of intercellular connections were noted in all ovaries studied. However, the bridges in each individual species usually exhibits one structural characteristic seldom found in the others. For example, bridges in the human ovary very often have large blebs projecting from the lateral borders whereas the sides of the connections in the mouse gonad merely demonstrate a slight convexity.



Author(s):  
Amreek Singh ◽  
Warren G. Foster ◽  
Anna Dykeman ◽  
David C. Villeneuve

Hexachlorobenzene (HCB) is a known toxicant that is found in the environment as a by-product during manufacture of certain pesticides. This chlorinated chemical has been isolated from many tissues including ovary. When administered in high doses, HCB causes degeneration of primordial germ cells and ovary surface epithelium in sub-human primates. A purpose of this experiment was to determine a no-effect dose of the chemical on the rat ovary. The study is part of a comprehensive investigation on the effects of the compound on the biochemical, hematological, and morphological parameters in the monkey and rat.



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