Dataset Information

Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules.

ABSTRACT: Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermatogonia using the Stra8 promoter was constructed to explore the roles of upregulated lncRNA-Gm2044 in male fertility. Testicular morphology and fertility weren't affected in transgenic mice expressing lncRNA-Gm2044. However, overexpression of lncRNA-Gm2044 in spermatogonia partially impaired spermatogenesis in the transgenic mice. Then, transcriptome sequencing was executed to find the potential signaling pathway repressing spermatogenesis in germ cells of lncRNA-Gm2044 transgenic mice. Through quantitative analysis of differentially expressed genes, 442 upregulated mRNAs and 147 downregulated mRNAs were displayed in male germ cells of Gm2044-transgenic mice (Gm2044-Tg) compared with non-transgenic mice (Non-Tg). Using gene ontology (GO) analysis, differentially expressed genes were shown to play vital roles in RNA_metabolic_process, Central_element, Enzyme_binding, and Intracellular_bridge. Using Kyoto encyclopedia of genes and genomes (KEGG) analysis, differentially expressed genes were shown to participate in RNA_transport, Cell_cycle, Renin-angiotensin_system, and Chemokine_signaling_pathway. Gene Set Enrichment Analysis (GSEA) revealed that Acrosome_assembly and Sperm_plasma_membrane were involved in the overexpression of lncRNA-Gm2044 blocking spermatogenesis. Furthermore, some of the most differentially expressed mRNAs were verified by RT-qPCR. In addition, we determined that the lncRNA-Gm2044 has no ability to translate into peptides by the bioinformatics method and molecular experiment. Thus, lncRNA-Gm2044 is a novel molecular target for the diagnosis and treatment of male infertility.

SUBMITTER: Hu K

PROVIDER: S-EPMC9192819 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules.

Hu Ke K Gao Yuanyuan Y Xu Yifan Y He Chaofan C Wang Kaixian K Li Leina L Liao Yaping Y Liu Xiaohua X Liang Meng M

Poultry science 20220427 7

Long noncoding RNAs (lncRNAs) have been demonstrated to regulate reproduction in mammals. Our previous study revealed that the expression level of lncRNA-Gm2044 was obviously elevated in nonobstructive azoospermia with spermatogonial arrest. Here, a transgenic mouse model of lncRNA-Gm2044 in spermatogonia using the Stra8 promoter was constructed to explore the roles of upregulated lncRNA-Gm2044 in male fertility. Testicular morphology and fertility weren't affected in transgenic mice expressing ...[more]

PMID: 35691049

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Project description:Study questionCan transplanted primate testicular cells form seminiferous tubules de novo, supporting complete spermatogenesis?Summary answerCryopreserved testicular cells from a prepubertal monkey can reorganize in an adult monkey recipient testis forming de novo seminiferous tubular cords supporting complete spermatogenesis.What is known alreadyDe novo morphogenesis of testicular tissue using aggregated cells from non-primate species grafted either subcutaneously or in the testis can support spermatogenesis.Study design, size, durationTwo postpubertal rhesus monkeys (Macaca mulatta) were given testicular irradiation. One monkey was given GnRH-antagonist treatment from 8 to 16 weeks after irradiation, while the other received sham injections. At 16 weeks, cryopreserved testicular cells from two different prepubertal monkeys [43 × 106 viable (Trypan-blue excluding) cells in 260 μl, and 80 × 106 viable cells in 400 μl] were transplanted via ultrasound-guided injections to one of the rete testis in each recipient, and immune suppression was given. The contralateral testis was sham transplanted. Testes were analyzed 9 months after transplantation.Participants/materials, setting, methodsSpermatogenic recovery was assessed by testicular volume, weight, histology and immunofluorescence. Microsatellite genotyping of regions of testicular sections obtained by LCM determined whether the cells were derived from the host or transplanted cells.Main results and the role of chanceTransplanted testis of the GnRH-antagonist-treated recipient, but not the sham-treated recipient, contained numerous irregularly shaped seminiferous tubular cords, 89% of which had differentiating germ cells, including sperm in a few of them. The percentages of donor genotype in different regions of this testis were as follows: normal tubule, 0%; inflammatory, 0%; abnormal tubule region, 67%; whole interior of abnormal tubules, >99%; adluminal region of the abnormal tubules, 92%. Thus, these abnormal tubules, including the enclosed germ cells, were derived de novo from the donor testicular cells.Large scale dataNot applicable.Limitations, reasons for cautionThe de novo tubules were observed in only one out of the two monkeys transplanted with prepubertal donor testicular cells.Wider implications of the findingsThese findings may represent a promising strategy for restoration of fertility in male childhood cancer survivors. The approach could be particularly useful in those exposed to therapeutic agents that are detrimental to the normal development of the tubule somatic cells affecting the ability of the endogenous tubules to support spermatogenesis, even from transplanted spermatogonial stem cells.Study funding/competing interest(s)This work was supported by research grants P01 HD075795 from Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD/NIH) to K.E.O and Cancer Center Support Grant P30 CA016672 from NCI/NIH to The University of Texas MD Anderson Cancer Center. The authors declare that they have no competing interests.

Project description:The study of spermatogenesis in the horse is challenging because of the absence of an in vitro system that is capable of reproducing efficient spermatogenesis and because of the difficulties and costs associated with performing well-controlled studies in vivo. In an attempt to develop novel methods for the study of equine spermatogenesis, we tested whether cells from enzymatically digested pre-pubertal equine testicular tissue were capable of de novo tissue formation and spermatogenesis following xenografting under the back skin of immunocompromised mice. Testes were obtained from normal pre-pubertal colts and dissociated into cell suspensions using trypsin/collagenase digestion. Resulting cell pellets, consisting of both somatic and germ cells, were injected into fascial pockets under the back skin of immunocompromised, castrated mice and maintained for between 1 and 14 months. Mice were killed and grafts were recovered and analyzed. As has been reported for testis cell suspensions from pigs, mice, cattle, and sheep, de novo formation of equine testicular tissue was observed, as evidenced by the presence of seminiferous tubules and an interstitial compartment. There was an increased likelihood of de novo testicular formation as grafting period increased. Using indirect immunofluorescence, we confirmed the presence of spermatogonia in de novo formed seminiferous tubules. However, we found no evidence of meiotic or haploid cells. These results indicate that dissociated pre-pubertal equine testis cells are capable of reorganizing into the highly specialized endocrine and spermatogenic compartments of the testis following ectopic xenografting. However, in spite of the presence of spermatogonia within the seminiferous tubules, spermatogenesis does not occur. Although this technique does allow access to the cells within the seminiferous tubule and interstitial compartments of the equine testis prior to reaggregation, the absence of spermatogenesis will limit its use as a method for the study of testicular function in the horse.

Project description:Objectives:Spermatogenesis is a regular and lengthy process in which the function of testicular cells may potentially be influenced by several extrinsic and intrinsic stressors, including environmental factors such as magnetic resonance imaging (MRI) waves and radiation. Our study aimed to investigate the effects of MRI waves and fields on the testicular histology and morphometry of seminiferous tubules in mice. Methods:The experiment was conducted on 40 adult Naval Medical Research Institute mice. The control group was located in the center of the MRI bore while it was turned off, while the exposed group was exposed to the active scanner for 36 minutes once a week for three weeks. Our study included four groups: group I (control group at one hour after last exposure), group II (experimental group at one hour after last exposure), group III (control group at 35 days after last virtual exposure), and group IV (experimental group at 35 days after last exposure). We then assessed the tube and lumen diameters, as well as epithelium thickness of the seminiferous tubules. Results:Our data showed that MRI waves partially reduced testicular weight one hour after the last exposure (group II) compared to group I (p = 0.240). On the other hand, in group II the Johnson's score (score 10, complete spermatogenesis and perfect tubules) was 87.5% which was slightly less than recorded in groups I, III, and IV (91.4%, 92.2%, and 90.5%, respectively). Furthermore, the MRI in group II revealed induces vacuolization in the epithelium, arrest in primary spermatocytes in the pachytene stage as well as disruption in the testicular parenchyma. Conclusions:Long-term exposure to MRI waves has deleterious effects on the male reproductive system, fertility parameters, and the quantity of germ cells in the seminiferous tubules with the exception of the number of round spermatid cells and epithelial thickness. All these effects were reversible after a new period of spermatogenesis.

Dataset Information

Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules.

Publications

Overexpression of lncRNA-Gm2044 in spermatogonia impairs spermatogenesis in partial seminiferous tubules.

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