scholarly journals Loss of protein phosphatase 1cγ (PPP1CC) leads to impaired spermatogenesis associated with defects in chromatin condensation and acrosome development: an ultrastructural analysis

Reproduction ◽  
2010 ◽  
Vol 139 (6) ◽  
pp. 1021-1029 ◽  
Author(s):  
Nicole Forgione ◽  
A Wayne Vogl ◽  
Susannah Varmuza

Human male infertility affects ∼5% of men, with one-third suffering from testicular failure, likely the result of an underlying genetic abnormality that disrupts spermatogenesis during development. Mouse models of male infertility such as thePpp1ccknockout mouse display very similar phenotypes to humans with testicular failure. MalePpp1ccmutant mice are sterile due to disruptions in spermatogenesis that begin during prepubertal testicular development, and continue into adulthood, often resulting in loss of germ cells to the point of Sertoli cell-only syndrome. The current study employs light and electron microscopy to identify new morphological abnormalities inPpp1ccmutant seminiferous epithelium. This study reveals that germ cells become delayed in their development around stages VII and VIII of spermatogenesis. Loss of these cells likely results in the reduced numbers of elongating spermatids and spermatozoa previously observed in mutant animals. Interestingly,Ppp1ccmutants also display reduced numbers of spermatogonia compared with their wild-type counterparts. Using electron microscopy, we have shown that junction complexes inPpp1ccmutants are ultrastructurally normal, and therefore do not contribute to the breakdown in tissue architecture seen in mutants. Electron microscopy revealed major acrosomal and chromatin condensation defects inPpp1ccmutants. Our observations are discussed in the context of known molecular changes inPpp1ccmutant testes.

Author(s):  
Judy Ju-Hu Chiang ◽  
Robert Kuo-Cheng Chen

Germ cells from the rice stem borer Chilo suppresalis, were examined by light and electron microscopy. Damages to organelles within the germ cells were observed. The mitochondria, which provide the cell with metabolic energy, were seen to disintegrate within the germ cell. Lysosomes within the germ cell were also seen to disintegrate. The subsequent release of hydrolytic enzymesmay be responsible for the destruction of organelles within the germ cell. Insect spermatozoa were seen to lose the ability to move because of radiation treatment. Damage to the centrioles, one of which is in contact with the tail, may be involved in causing sperm immobility.


1956 ◽  
Vol 6 (2) ◽  
pp. 272-278
Author(s):  
Cecilie Leuchtenberger ◽  
D.R. Weir ◽  
F. Schrader ◽  
R. Leuchtenberger

2003 ◽  
Vol 69 (3) ◽  
pp. 746-751 ◽  
Author(s):  
J.Y.M. Tse ◽  
E.Y.M. Wong ◽  
A.N.Y. Cheung ◽  
W.S. O ◽  
P.C. Tam ◽  
...  

2001 ◽  
Vol 22 (2) ◽  
pp. 217-233 ◽  
Author(s):  
Guarino Colli ◽  
Gustavo H.C. Vieira ◽  
Sônia Báo ◽  
Helga Wiederhecker

AbstractWe studied the spermiogenesis and testicular cycle of the lizard Tropidurus torquatus, using light and electron microscopy. Males bearing spermatozoa were present practically year-round and spermatogenic activity showed a regenerative phase from late dry season to the end of the rainy season (July to March), with low frequency of initial stages of the spermatogenic cycle, and a brief degenerative phase from April to June, lacking the total regression of seminiferous tubules. These characteristics resemble those from species with continuous reproductive cycles, contrasting with the strongly seasonal reproductive cycle of females. Spermiogenesis includes nuclear elongation, chromatin condensation, acrosomal and flagellar development, and elimination of excessive cytoplasm. We describe some new aspects in the spermiogenesis of T. torquatus, including the interaction between spermatid and Sertoli cell, acrosomal granule, subacrosomal granule, and the fibrous sheath formation. The testicular cycle of T. torquatus is very similar to that of other lizards that inhabit seasonal environments, and its spermiogenesis and ultrastructure of mature sperm display a number of conservative features.


Blood ◽  
1964 ◽  
Vol 23 (3) ◽  
pp. 300-320 ◽  
Author(s):  
ROBERT J. CAPONE ◽  
EVA LURIE WEINREB ◽  
GEORGE B. CHAPMAN

Abstract The development of representative myeloid elements is traced by correlated light and electron microscopy. Cytoplasmic changes during maturation of granulocytes from the myeloblast include loss of basophilia, development of the endoplasmic reticulum complex, decrease in number of mitochondria, and granule formation. The endoplasmic reticulum vesicles increase in size and number during the promyelocyte and myelocyte stages, accompanied by the appearance of non-specific and specific granules, and decrease again during the cytosomal maturation of the metamyelocyte. A reduction in number of mitochondria is noted through the metamyelocyte stage. The apparent continuity of the limiting membranes of both the granules and mitochondria with those of the cisternae of endoplasmic reticulum suggests a direct connection among cytosomal organelles. The role of the endoplasmic reticulum in granulogenesis is discussed. Maturation of the nucleus involves a loss of nucleolar differentiation by a loosening of the compact fibrillar aggregates, and progressive chromatin condensation.


2020 ◽  
Vol 18 (1) ◽  
Author(s):  
Meghali Joshi ◽  
Singh Rajender

Abstract Background Long non-coding RNAs (lncRNAs) have a size of more than 200 bp and are known to regulate a host of crucial cellular processes like proliferation, differentiation and apoptosis by regulating gene expression. While small noncoding RNAs (ncRNAs) such as miRNAs, siRNAs, Piwi-interacting RNAs have been extensively studied in male germ cell development, the role of lncRNAs in spermatogenesis remains largely unknown. Objective In this article, we have reviewed the biology and role of lncRNAs in spermatogenesis along with the tools available for data analysis. Results and conclusions Till date, three microarray and four RNA-seq studies have been undertaken to identify lncRNAs in mouse testes or germ cells. These studies were done on pre-natal, post-natal, adult testis, and different germ cells to identify lncRNAs regulating spermatogenesis. In case of humans, five RNA-seq studies on different germ cell populations, including two on sperm, were undertaken. We compared three studies on human germ cells to identify common lncRNAs and found 15 lncRNAs (LINC00635, LINC00521, LINC00174, LINC00654, LINC00710, LINC00226, LINC00326, LINC00494, LINC00535, LINC00616, LINC00662, LINC00668, LINC00467, LINC00608, and LINC00658) to show consistent differential expression across these studies. Some of the targets of these lncRNAs included CENPB, FAM98B, GOLGA6 family, RPGR, TPM2, GNB5, KCNQ10T1, TAZ, LIN28A, CDKN2B, CDKN2A, CDKN1A, CDKN1B, CDKN1C, EZH2, SUZ12, VEGFA genes. A lone study on human male infertility identified 9879 differentially expressed lncRNAs with three (lnc32058, lnc09522, and lnc98497) of them showing specific and high expression in immotile sperm in comparison to normal motile sperm. A few lncRNAs (Mrhl, Drm, Spga-lncRNAs, NLC1-C, HongrES2, Tsx, LncRNA-tcam1, Tug1, Tesra, AK015322, Gm2044, and LncRNA033862) have been functionally validated for their roles in spermatogenesis. Apart from rodents and humans, studies on sheep and bull have also identified lncRNAs potentially important for spermatogenesis. A number of these non-coding RNAs are strong candidates for further research on their roles in spermatogenesis.


Science ◽  
2013 ◽  
Vol 343 (6166) ◽  
pp. 69-72 ◽  
Author(s):  
Yasuhiro Yamauchi ◽  
Jonathan M. Riel ◽  
Zoia Stoytcheva ◽  
Monika A. Ward

The Y chromosome is thought to be important for male reproduction. We have previously shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factorSryand the spermatogonial proliferation factorEif2s3y.Sryis believed to function primarily in sex determination during fetal life.Eif2s3ymay be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.


2021 ◽  
Author(s):  
Lucia A. Torres-Fernández ◽  
Jana Emich ◽  
Yasmine Port ◽  
Sibylle Mitschka ◽  
Marius Wöste ◽  
...  

AbstractMutations affecting the germline can result in infertility or the generation of germ cell tumors (GCT), highlighting the need to identify and characterize the genes controlling the complex molecular network orchestrating germ cell development. TRIM71 is a stem cell-specific factor essential for embryogenesis, and its expression has been reported in GCT and adult mouse testes. To investigate the role of TRIM71 in mammalian germ cell embryonic development, we generated a germline-specific conditional Trim71 knockout mouse (cKO) using the early primordial germ cell (PGC) marker Nanos3 as a Cre-recombinase driver. cKO mice are infertile, with male mice displaying a Sertoli cell-only (SCO) phenotype, which in humans is defined as a specific subtype of non-obstructive azoospermia characterized by the absence of developing germ cells in the testes’ seminiferous tubules. Infertility originates during embryogenesis, as the SCO phenotype was already apparent in neonatal mice. The in vitro differentiation of mouse embryonic stem cells (ESCs) into PGC-like cells (PGCLCs) revealed reduced numbers of PGCLCs in Trim71-deficient cells. Furthermore, in vitro growth competition assays with wild type and CRISPR/Cas9-generated TRIM71 mutant NCCIT cells, a human GCT-derived cell line which we used as a surrogate model for proliferating PGCs, showed that TRIM71 promotes NCCIT cell proliferation and survival. Our data collectively suggest that germ cell loss in cKO mice results from combined defects during the specification and maintenance of PGCs prior to their sex determination in the genital ridges. Last, via exome sequencing analysis, we identified several TRIM71 variants in a cohort of infertile men, including a loss-of-function variant in a patient with SCO phenotype. Our work reveals for the first time an association of TRIM71 variants with human male infertility, and uncovers further developmental roles for TRIM71 in the generation and maintenance of germ cells during mouse embryogenesis.


2015 ◽  
Vol 27 (1) ◽  
pp. 140
Author(s):  
N. Tiptanavattana ◽  
A. Radtanakatikanon ◽  
S. Buranapraditkun ◽  
P. Hyttel ◽  
H. M. Holmes ◽  
...  

The pubertal age of domestic cat (Felis catus) as defined as a complete spermatogenesis has been reported to occur around 8 months of age. During the initial phase of testicular development, the transition of gonocytes to spermatogonial stem cells (SSC) takes place within the seminiferous cords. This stage-specific transition has been demonstrated to facilitate SSC isolation and enrichment. Because information for this aspect in domestic cats is limited, this study aimed to identify the phase transition of gonocytes to SSC during newborn to puberty. Cat testes were collected and classified by age into 3 groups: group 1: 0–4 months (n = 5), group 2: 4–6 months (n = 5), and group 3: 6–12 months (n = 5). Testes were studied for conventional histology, transmission electron microscopy (TEM), and FACS analysis on GFRα-1 expression, a SSC marker. For histology, tissues were fixed, sectioned, and stained with H&E. Serial changes of germ cell development within the testes were observed using light microscopy. In addition, ultrathin sections (60 nm thickness) of testes were cut and examined with TEM for ultrastructure analysis. Immunolabelling and flow cytometry of GFRα-1 were used to identify the SSC population after testicular cell dissociation. The percentages of spermatogonia per tubule were analysed by one-way ANOVA, and data are presented as mean ± s.e. The development of testicular germ cells from gonocyte to spermatozoon was gradually demonstrated in histological sections, depending on age of the cats. For group 1, the gonocytes were clearly presented in the seminiferous cord. These gonocytes were in proliferative phase, as they frequently contained homogeneous euchromatin and less organelles. In group 2, the gonocytes transformed to spermatogonia as indicated by their small size (range 8.11–13.55 μm) with oval to flattened shape, chromatin condensation, and darkened cytoplasm. These cells migrated and settled onto the basement membrane of seminiferous cord. At this stage, mitochondria and small clumps of heterochromatin increased when compared with group 1. Some spermatogonia occasionally developed through the meiosis by 6 months of age (group 2), whereas complete spermatogenesis was first identified in 9-month testes (group 3). The percentage of spermatogonium/tubule in group 2 (15.84 ± 0.67) was significantly higher (P < 0.001) than group 1 and 3 (1.99 ± 0.22 and 6.88 ± 0.53, respectively). Because the SSC-like cells (based on their histological morphology) were predominantly found in group 2, the testes (n = 5, 4–6 months of age) were additionally digested to confirm GFRα-1 expression. Of total testicular cells, a high proportion of GFRα-1 positive cells (12.32 ± 6.31%) were identified by FACS. In conclusion, this study provides information regarding the age-dependent development of testicular germ cells in domestic cats. The findings provide the transition period of gonocytes to SSC that occurs around 4 to 6 months of age. This study can be applied for the enrichment of feline SSC upon testicular digestion.


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