scholarly journals Apoptosis in the fetal testis eliminates developmentally defective germ cell clones

2019 ◽  
Author(s):  
Daniel H. Nguyen ◽  
Diana J. Laird

SummaryMany germ cells (GCs) are eliminated during development, long before differentiating to egg or sperm, but it is not clear why. Here, we examined how GC composition in the mouse fetal testis is altered by scheduled apoptosis during sex differentiation. Multicolored-lineage tracing revealed that apoptosis affects clonally-related GCs, suggesting that this fate decision occurs autonomously based on shared intrinsic properties. We identified extensive transcriptional heterogeneity among fetal GCs including an apoptosis-susceptible subpopulation delineated by high Trp53 and deviant differentiation. Alternatively, the GC subpopulation most likely to survive was advanced in differentiation. These results indicate that GC developmental fate is based upon discrete and cell-heritable fitnesses and imply that a dichotomy between sex-differentiation and apoptosis coordinates the removal of developmentally incompetent cells to improve gamete quality. Evidence that GC subpopulations are in different epigenetic states suggests that errors in epigenetic reprogramming form the basis of aberrant differentiation and apoptotic selection.One sentence summaryGerm cells undergo autonomous selection in the fetal testis to promote male differentiation


Endocrinology ◽  
2007 ◽  
Vol 149 (4) ◽  
pp. 1813-1819 ◽  
Author(s):  
Eri Shiraishi ◽  
Norifumi Yoshinaga ◽  
Takeshi Miura ◽  
Hayato Yokoi ◽  
Yuko Wakamatsu ◽  
...  

Müllerian inhibiting substance (MIS) is a glycoprotein belonging to the TGF-β superfamily. In mammals, MIS is responsible for the regression of Müllerian ducts in the male fetus. However, the role of MIS in gonadal sex differentiation of teleost fish, which have no Müllerian ducts, has yet to be clarified. In the present study, we examined the expression pattern of mis and mis type 2 receptor (misr2) mRNAs and the function of MIS signaling in early gonadal differentiation in medaka (teleost, Oryzias latipes). In situ hybridization showed that both mis and misr2 mRNAs were expressed in the somatic cells surrounding the germ cells of both sexes during early sex differentiation. Loss-of-function of either MIS or MIS type II receptor (MISRII) in medaka resulted in suppression of germ cell proliferation during sex differentiation. These results were supported by cell proliferation assay using 5-bromo-2′-deoxyuridine labeling analysis. Treatment of tissue fragments containing germ cells with recombinant eel MIS significantly induced germ cell proliferation in both sexes compared with the untreated control. On the other hand, culture of tissue fragments from the MIS- or MISRII-defective embryos inhibited proliferation of germ cells in both sexes. Moreover, treatment with recombinant eel MIS in the MIS-defective embryos dose-dependently increased germ cell number in both sexes, whereas in the MISRII-defective embryos, it did not permit proliferation of germ cells. These results suggest that in medaka, MIS indirectly stimulates germ cell proliferation through MISRII, expressed in the somatic cells immediately after they reach the gonadal primordium.



Development ◽  
1962 ◽  
Vol 10 (4) ◽  
pp. 465-470
Author(s):  
Charles L. Foote ◽  
Florence M. Foote

Earlier reports (Foote & Foote, 1958a, b, 1959) describe growth and maintenance in vitro of larval organs, particularly gonads, of Rana catesbeiana and Xenopus laevis. Immature germ cells of both testes and ovaries are well maintained in vitro, especially if the culture medium is supplemented with watersoluble sex-hormonal substances, although germ cells in process of maturation become necrotic. Recently some urogenital organs from the salamander, Pleurodeles waltlii, have been grown in vitro. Tissues and organs from this amphibian might prove to be more suitable for tissue and organ culture investigations than those of Anurans. Animals at three different ages were used in this study: recently hatched larvae, metamorphosing animals, and adults. To determine whether sex differentiation would occur in vitro, trunk portions of young larvae of Pleurodeles waltlii of developmental stages 37–38 (Gallien & Durocher, 1957) were placed in organ cultures.



Development ◽  
1972 ◽  
Vol 28 (2) ◽  
pp. 385-395
Author(s):  
Noriyuki Satoh ◽  
Nobuo Egami

Mitotic and meiotic activities of germ cells during early development in the medaka, Oryzias latipes, are dealt with in this report. Primordial germ cells were obviously distinguishable from somatic cells 3 days after fertilization and began to proliferate about 7 days after fertilization. The mean number of primordial germ cells increased during a period of 7–10 days after fertilization, reaching about 90 immediately before hatching. Newly hatched fry could be classified into two types according to the number and the nucleic activity of germ cells in the gonadal rudiment. One type consisted of fry containing about 100 germ cells and no cells in the meiotic prophase. In the other type of fry the number of germ cells increased by mitotic divisions and some of the cells began to enter into the meiotic prophase. During the course of further development the fry of the former type differentiated into males and the latter into females. Therefore it can be concluded that the morphological sex differentiation of germ cells occurs at the time of hatching. However, no sexual differences in the histological structure of somatic elements in the gonad are observable at that time.



1941 ◽  
Vol 69 (1) ◽  
pp. 51-81 ◽  
Author(s):  
Kenneth L. Duke


2018 ◽  
Author(s):  
Boris Reznik ◽  
Steven A. Cincotta ◽  
Rebecca G. Jaszczak ◽  
Leslie J. Mateo ◽  
Joel Shen ◽  
...  

AbstractEpigenetic resetting in germ cells during development leads to the de-repression of transposable elements (TEs). piRNAs protect fetal germ cells from potentially harmful TEs by targeted destruction of mRNA and deposition of repressive epigenetic marks. Here we provide the first evidence for an active piRNA pathway and TE repression in germ cells of human fetal testis. We identify pre-pachytene piRNAs with features of secondary amplification that map most abundantly to L1 family TEs. We find that L1-ORF1p expression is heterogeneous in fetal germ cells, peaks at mid-gestation and declines concomitantly with increasing levels of piRNAs and H3K9me3, as well as nuclear localization of HIWI2. Surprisingly, following this decline, the same cells with accumulation of L1-ORF1p display highest levels of HIWI2 and H3K9me3, whereas L1-ORF1p low cells are also low in HIWI2 and H3K9me3. Conversely, earlier in development, the germ cells lacking L1-ORF1p express high levels of the chaperone HSP90a. We propose that a subset of HSP90a-armed germ cells resists L1 expression, whereas only those vulnerable L1-expressing germ cells activate the PIWI-piRNA repression pathway which leads to epigenetic silencing of L1 via H3K9me3.



2018 ◽  
Vol 100 (3) ◽  
pp. 697-710 ◽  
Author(s):  
Akihiko Sakashita ◽  
Takuya Wakai ◽  
Yukiko Kawabata ◽  
Chiaki Nishimura ◽  
Yusuke Sotomaru ◽  
...  

Abstract The fertility of sex-reversed XY female mice is severely impaired by a massive loss of oocytes and failure of meiotic progression. This phenomenon remains an outstanding mystery. We sought to determine the molecular etiology of XY oocyte dysfunction by generating sex-reversed females that bear genetic ablation of Sry, a vital sex determination gene, on an inbred C57BL/6 background. These mutant mice, termed XYsry− mutants, showed severe attrition of germ cells during fetal development, resulting in the depletion of ovarian germ cells prior to sexual maturation. Comprehensive transcriptome analyses of primordial germ cells (PGCs) and postnatal oocytes demonstrated that XYsry− females had deviated significantly from normal developmental processes during the stages of mitotic proliferation. The impaired proliferation of XYsry− PGCs was associated with aberrant β-catenin signaling and the excessive expression of transposable elements. Upon entry to the meiotic stage, XYsry− oocytes demonstrated extensive defects, including the impairment of crossover formation, the failure of primordial follicle maintenance, and no capacity for embryo development. Together, these results suggest potential molecular causes for germ cell disruption in sex-reversed female mice, thereby providing insights into disorders of sex differentiation in humans, such as “Swyer syndrome,” in which patients with an XY karyotype present as typical females and are infertile.



2008 ◽  
Vol 78 (Suppl_1) ◽  
pp. 272-272
Author(s):  
Yukiko Yamazaki ◽  
Hirotaka Yoshioka ◽  
John R McCarrey ◽  
Ryuzo Yanagimachi ◽  
Kazuhiro Iwahashi


2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Lianne Kok ◽  
Feline E. Dijkgraaf ◽  
Jos Urbanus ◽  
Kaspar Bresser ◽  
David W. Vredevoogd ◽  
...  

An increasing body of evidence emphasizes the role of tissue-resident memory T cells (TRM) in the defense against recurring pathogens and malignant neoplasms. However, little is known with regard to the origin of these cells and their kinship to other CD8+ T cell compartments. To address this issue, we followed the antigen-specific progeny of individual naive CD8+ T cells to the T effector (TEFF), T circulating memory (TCIRCM), and TRM pools by lineage-tracing and single-cell transcriptome analysis. We demonstrate that a subset of T cell clones possesses a heightened capacity to form TRM, and that enriched expression of TRM–fate-associated genes is already apparent in the circulating TEFF offspring of such clones. In addition, we demonstrate that the capacity to generate TRM is permanently imprinted at the clonal level, before skin entry. Collectively, these data provide compelling evidence for early stage TRM fate decisions and the existence of committed TRM precursor cells in the circulatory TEFF compartment.



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