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Project description:The tumor suppressor PTEN regulates negatively Sertoli cell proliferation, testis size and sperm production in vivo
| PRJNA507599 | ENA
Project description:Understanding why there is extensive variation in sperm form and function across taxa has been a challenge because sperm are specialized cells operating at a microscopic level in a complex environment. This comparative study collates published data to determine whether the evolution of sperm morphometry (sperm total length and separate component dimensions) is associated with sperm competition (when different males' sperm mix and compete for a female's ova) across 83 mammalian species. We use relative testes mass as an indicator of the intensity of sperm competition across taxa: relative investment into testes is widely accepted to predict the level of sperm competition that a species or population endures. Although we found evidence for positive associations between relative testes mass (controlling for allometry) and sperm morphometry across 83 mammalian species, these relationships were phylogenetically dependent. When we appropriately controlled for phylogenetic association using multiple regression within a phylogenetic framework, there was no relationship between relative testes mass and sperm length across mammals. Furthermore, we found no evidence for associations between relative testes mass and sperm head, mid-piece or flagellar lengths, nor was there a relationship with mid-piece or mitochondrial volumes. Results, therefore, indicate that sperm competition does not select for longer or shorter sperm across mammals, and alternative forces selecting on sperm form and function are discussed.
| S-EPMC1691278 | biostudies-literature
Project description:LIM and SH3 protein 1 (LASP1) enhances tumor growth and metastasis in various cancers, but its role in nasopharyngeal carcinoma (NPC) remains unclear. Herein, we investigated the role of LASP1 in NPC and explored the underlying mechanisms in NPC. Clinically, overexpression of LASP1 is associated with tumor metastasis and poor prognosis of NPC patients. Gain-of-function and loss-of-function assays showed that LASP1 promoted NPC cell proliferation, metastasis, and invasion in vitro and in vivo. Mechanistically, we observed clear co-localization between LASP1 and PTEN in NPC cells. LASP1 interacted with PTEN and decreased the expression of PTEN in NPC. The ubiquitination assay indicated that LASP1 overexpression increased PTEN ubiquitination. PTEN was known as a tumor suppressor by negatively regulating phosphoinositide 3-kinase/AKT signaling pathway. Rescue experiments showed that PTEN weakened LASP1-mediated cell proliferation, migration, and invasive abilities and decreased the phosphorylation of AKT in NPC cells. Our findings suggest that LASP1 has a crucial role in NPC progression via LASP1/PTEN/AKT axis, highlighting LASP1 as a therapeutic target for NPC.
| S-EPMC5847534 | biostudies-literature
Project description:Spermatogenesis is a costly process that is expected to be under selection to maximise sperm quantity and quality. Testis size is often regarded as a proxy measure of sperm investment, implicitly overlooking the quantitative assessment of spermatogenesis. An enhanced understanding of testicular function, beyond testis size, may reveal further sexual traits involved in sperm quantity and quality. Here, we first estimated the inter-male variation in testicular function and sperm traits in red deer across the breeding and non-breeding seasons. Then, we analysed the relationships between the testis mass, eight parameters of spermatogenic function, and seven parameters of sperm quality. Our findings revealed that the Sertoli cell number and function parameters vary greatly between red deer males, and that spermatogenic activity co-varies with testis mass and sperm quality across the breeding and non-breeding seasons. For the first time in a seasonal breeder, we found that not only is the Sertoli cell number important in determining testis mass (r = 0.619, p = 0.007 and r = 0.248, p = 0.047 for the Sertoli cell number assessed by histology and cytology, respectively), but also sperm function (r = 0.703, p = 0.002 and r = 0.328, p = 0.012 for the Sertoli cell number assessed by histology and cytology, respectively). Testicular histology also revealed that a high Sertoli cell number per tubular cross-section is associated with high sperm production (r = 0.600, p = 0.009). Sperm production and function were also positively correlated (r = 0.384, p = 0.004), suggesting that these traits co-vary to maximise sperm fertilisation ability in red deer. In conclusion, our findings contribute to the understanding of the dynamics of spermatogenesis, and reveal new insights into the role of testicular function and the Sertoli cell number on testis size and sperm quality in red deer.
| S-EPMC4592251 | biostudies-literature
Project description:Background: In polygynous species, the development of secondary sexual characters is usually decisive for male reproductive success. However, our understanding about the links between the growth of these traits and reproductive efficiency is still elusive. Most research efforts in this topic have been also focused on adult males, although the development of some secondary sexual characters, like bovid horns, typically starts after birth, continues during the puberty and in some species, such as the common eland, slows or even stops during adulthood. In this study, we investigated the relationships between horn size and testicular function during sexual development in common elands using a comprehensive approach that considers both spermatogenic and sperm parameters. Methods: Twenty-two non-sexually mature common elands were used for the present study. Horn size, body mass, testes mass, and gonadosomatic index were assessed. Spermatogenic activity was determined by cytological and histological analyses. Sperm concentration, morphology, morphometry, and intramale variation in sperm size were evaluated on epididymal sperm samples. Cluster analysis was performed to explore the influence of age on relationships between horn size and reproductive function. Results: We found that bigger horns are associated with increased Sertoli cell efficiency and reduced intramale variation in sperm size. Both parameters were not related to one another while they have shown to be associated with enhanced sperm quality in ungulates. Moreover, horn size was positively linked to the testis mass, sperm concentration, and testicular investment in the seminiferous epithelium. Spiral length and basal circumference were the horn traits most strongly correlated with spermatogenic and sperm parameters as well as those responsible for the sexual dimorphism in this species. Cluster analysis rendered two groups: the first one including males ≤30 months old, while the second one those >30 months old. Horn development and reproductive function were still correlated within age groups, with the strongest relationship found between horn size and sperm size homogeneity in males >30 months old. Conclusion: Taken together, our results indicate that horn size can be regarded as a good index of male reproductive potential during sexual development and provide insights into the role of secondary sexual characters in sexual selection dynamics.
| S-EPMC11368866 | biostudies-literature
Project description:A thorough understanding of the events during mammalian spermatogenesis requires studying specific molecular signatures of individual testicular cell populations as well as their interaction in co-cultures. However, most purification techniques to isolate specific testicular cell populations are time-consuming, require large numbers of animals, and/or are only able to isolate a few cell types. Here we describe a cost-effective and timesaving approach that uses a single protocol to enrich multiple testicular cell populations (Sertoli, Leydig, and several spermatogenic cell populations) from as few as one mouse. Our protocol combines rigorous enzymatic digestion of seminiferous tubules with counter-current centrifugal elutriation, yielding specific testicular cell populations with >80%-95% purity.
| S-EPMC3774005 | biostudies-literature
Project description:The conformation and function of a subset of serine and threonine-phosphorylated proteins are regulated by the prolyl isomerase Pin1 through isomerization of phosphorylated Ser/Thr-Pro bonds. Pin1 is intensely expressed in Sertoli cells, but its function in this post mitotic cell remains unclear. Our aim was to investigate the role of Pin1 in the Sertoli cells. Lack of Pin1 caused disruption of the blood-testis barrier. We next investigated if the activin pathways in the Sertoli cells were affected by lack of Pin1 through immunostaining for Smad3 protein in testis tissue. Indeed, lack of Pin1 caused reduced Smad3 expression in the testis tissue, as well as a reduction in the level of N-Cadherin, a known target of Smad3. Pin1-/- testes express Sertoli cell marker mRNAs in a pattern similar to that seen in Smad3+/- mice, except for an increase in Wt1 expression. The resulting dysregulation of N-Cadherin, connexin 43, and Wt1 targets caused by lack of Pin1 might affect the mesenchymal-epithelial balance in the Sertoli cells and perturb the blood-testis barrier. The effect of Pin1 dosage in Sertoli cells might be useful in the study of toxicant-mediated infertility, gonadal cancer, and for designing male contraceptives.
| S-EPMC5539286 | biostudies-literature
Project description:Spermatogenesis is a complex process that establishes male fertility and involves proper communication between the germline (spermatozoa) and the somatic tissue (Sertoli cells). Many factors that are important for spermatozoa production are also required for Sertoli cell function. Recently, we showed that the transcriptional cofactor ubiquitously expressed transcript (UXT) encodes a protein that is essential in germ cells for spermatogenesis and fertility. However, the role of UXT within Sertoli cells and how it affects Sertoli cell function was still unclear. Here we describe a novel role for UXT in the Sertoli cell's ability to support spermatogenesis. We find that the conditional deletion of Uxt in Sertoli cells results in smaller testis size and weight, which coincided with a loss of germ cells in a subset of seminiferous tubules. In addition, the deletion of Uxt has no impact on Sertoli cell abundance or maturity, as they express markers of mature Sertoli cells. Gene expression analysis reveals that the deletion of Uxt in Sertoli cells reduces the transcription of genes involved in the tight junctions of the blood-testis barrier (BTB). Furthermore, tracer experiments and electron microscopy reveal that the BTB is permeable in UXT KO animals. These findings broaden our understanding of UXT's role in Sertoli cells and its contribution to the structural integrity of the BTB.
| S-EPMC7569350 | biostudies-literature
Project description:The mammalian nuclear hormone receptors LRH1 and SF1 are close paralogs that can bind the same DNA site and play crucial roles in gonadal development and function. Lrh1 has been shown to be essential for follicle development in the ovary and also has been proposed to regulate steroidogenesis in the testis, but genetic analysis of its role in the male gonad has not been reported. Here we use conditional genetics to examine Lrh1 requirements in gonadal cell fate reprogramming and in normal development of the three major cell lineages of the mouse testis. Lrh1 expression is highly elevated by loss of the sex regulator Dmrt1, which triggers male-to-female transdifferentiation of Sertoli cells. We found that loss of Lrh1 suppresses this transdifferentiation, confirming that Lrh1 can act as a key driver in reprogramming sexual cell fate. In otherwise wild-type testes we found that Lrh1 is dispensable in Leydig cells but is required in Sertoli cells for their proliferation, for seminiferous tubule morphogenesis, for maintenance of the blood-testis barrier, for feedback regulation of androgen production, and for support of spermatogenesis. Expression profiling identified misexpressed genes likely underlying most aspects of the Sertoli cell phenotype. In the germ line Lrh1 is required for maintenance of spermatogonial stem cells (SSCs) and mutants progressively lose spermatogenesis. Reduced expression of the RNA binding factor Nxf2 likely contributes to the SSC maintenance defect. Unexpectedly, however, the Lrh1 mutant germ line can recover abundant spermatogenesis and fertility. This finding suggests the presence of a reserve stem cell population with different genetic requirements from the stem cells that normally support steady state spermatogenesis. Together our results demonstrate that Lrh1, like Sf1, is an essential regulator of testis development and function but has a distinct repertoire of functions.
2022-02-10 | GSE180204 | GEO
Project description:BackgroundDuring epididymal transit, spermatozoa go through several functional maturation steps, resulting from interactions with epididymal secretomes specific to each region. In particular, the sperm membrane is under constant remodeling, with sequential attachment and shedding of various molecules provided by the epididymal lumen fluid and epididymosomes, which also deliver sncRNA cargo to sperm. As a result, the payload of sperm sncRNAs changes during the transit from the epididymis caput to the cauda. This work was designed to study the dynamics of cattle sperm sncRNAs from spermatogenesis to final maturation.ResultsComprehensive catalogues of sperm sncRNAs were obtained from testicular parenchyma, epididymal caput, corpus and cauda, as well as ejaculated semen from three Holstein bulls. The primary cattle sncRNA sperm content is markedly remodeled as sperm mature along the epididymis. Expression of piRNAs, which are abundant in testis parenchyma, decreases dramatically at epididymis. Conversely, sperm progressively acquires miRNAs, rsRNAs, and tsRNAs along epididymis, with regional specificities. For instance, miRNAs and tsRNAs are enriched in epididymis cauda and ejaculated sperm, while rsRNA expression peaks at epididymis corpus. In addition, epididymis corpus contains mainly 20 nt long piRNAs, instead of 30 nt in all other locations. Beyond the bulk differences in abundance of sncRNAs classes, K-means clustering was performed to study their spatiotemporal expression profile, highlighting differences in specific sncRNAs and providing insights into their putative biological role at each maturation stage. For instance, Gene Ontology analyses using miRNA targets highlighted enriched processes such as cell cycle regulation, response to stress and ubiquitination processes in testicular parenchyma, protein metabolism in epididymal sperm, and embryonic morphogenesis in ejaculated sperm.ConclusionsOur findings confirm that the sperm sncRNAome does not simply reflect a legacy of spermatogenesis. Instead, sperm sncRNA expression shows a remarkable level of plasticity resulting probably from the combination of multiple factors such as loss of the cytoplasmic droplet, interaction with epididymosomes, and more surprisingly, the putative in situ production and/or modification of sncRNAs by sperm. Given the suggested role of sncRNA in epigenetic trans-generational inheritance, our detailed spatiotemporal analysis may pave the way for a study of sperm sncRNAs role in embryo development.
| S-EPMC8146655 | biostudies-literature