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International Journal of Molecular... May 2024The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and... (Review)
Review
The testes serve as the primary source of androgens and the site of spermatogenesis, with their development and function governed by hormonal actions via endocrine and paracrine pathways. Male fertility hinges on the availability of testosterone, a cornerstone of spermatogenesis, while follicle-stimulating hormone (FSH) signaling is indispensable for the proliferation, differentiation, and proper functioning of Sertoli and germ cells. This review covers the research on how androgens, FSH, and other hormones support processes crucial for male fertility in the testis and reproductive tract. These hormones are regulated by the hypothalamic-pituitary-gonad (HPG) axis, which is either quiescent or activated at different stages of the life course, and the regulation of the axis is crucial for the development and normal function of the male reproductive system. Hormonal imbalances, whether due to genetic predispositions or environmental influences, leading to hypogonadism or hypergonadism, can precipitate reproductive disorders. Investigating the regulatory network and molecular mechanisms involved in testicular development and spermatogenesis is instrumental in developing new therapeutic methods, drugs, and male hormonal contraceptives.
Topics: Humans; Male; Testis; Animals; Spermatogenesis; Follicle Stimulating Hormone; Hypothalamo-Hypophyseal System; Androgens; Testosterone
PubMed: 38891991
DOI: 10.3390/ijms25115805 -
International Journal of Molecular... May 2024The dynamic process of spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders...
The dynamic process of spermatogenesis involves asymmetric division, mitosis, and meiosis, which ultimately results in the production of mature spermatozoa. Disorders of spermatogenesis can lead to infertility in males. ADAR (adenosine deaminase acting on RNA) mutations in cause male infertility, yet the causative factors remain unclear. In this study, immunofluorescence staining was employed to visualize endogenous ADAR proteins and assess protein levels via fluorescence-intensity analysis. In addition, the early differentiation disorders and homeostatic alterations during early spermatogenesis in the testes were examined through quantification of transit-amplifying region length, counting the number of GSCs (germline stem cells), and fertility experiments. Our findings suggest that deletion of ADAR causes testicular tip transit-amplifying cells to accumulate and become infertile in older male . By overexpressing ADAR in early germline cells, male infertility can be partially rescued. Transcriptome analysis showed that ADAR maintained early spermatogenesis homeostasis through the bone-morphogenetic-protein (BMP) signaling pathway. Taken together, these findings have the potential to help explore the role of ADAR in early spermatogenesis.
Topics: Animals; Male; Spermatogenesis; Drosophila melanogaster; Signal Transduction; Drosophila Proteins; Adenosine Deaminase; Bone Morphogenetic Proteins; Infertility, Male; RNA-Binding Proteins; Testis
PubMed: 38891830
DOI: 10.3390/ijms25115643 -
International Journal of Molecular... May 2024The testis-specific double sex and mab-3-related transcription factor 1 () has long been recognized as a crucial player in sex determination across vertebrates, and its...
The testis-specific double sex and mab-3-related transcription factor 1 () has long been recognized as a crucial player in sex determination across vertebrates, and its essential role in gonadal development and the regulation of spermatogenesis is well established. Here, we report the cloning of the key spermatogenesis-related cDNA, named , from the gonads of (), with a molecular weight of 41.93 kDa and an isoelectric point of 7.83 (pI). Our hypothesis is that machinery governs spermatogenesis and regulates gonadogenesis. RNAi-mediated knockdown revealed its critical role in hindering spermatogenesis and reducing expression levels in boring giant clams. A histological analysis showed structural changes, with normal sperm cell counts in the control group (ds-EGFP) but significantly lower concentrations of sperm cells in the experimental group (). transcripts during embryogenesis exhibited a significantly high expression pattern ( < 0.05) during the early zygote stage, and whole-embryo in-situ hybridization confirmed its expression pattern throughout embryogenesis. A qRT-PCR analysis of various reproductive stages revealed an abundant expression of in the gonads during the male reproductive stage. In-situ hybridization showed tissue-specific expression of , with a positive signal detected in male-stage gonadal tissues comprising sperm cells, while no signal was detected in other stages. Our study findings provide an initial understanding of the molecular machinery controlling spermatogenesis and its specificity in male-stage gonads of the key bivalve species, , and suggest that predominantly functions as a key regulator of spermatogenesis in giant clams.
Topics: Animals; Spermatogenesis; Transcription Factors; Male; Testis; Bivalvia; Gene Expression Regulation, Developmental; Gonads; Hermaphroditic Organisms; Cloning, Molecular; Phylogeny; Amino Acid Sequence
PubMed: 38891762
DOI: 10.3390/ijms25115574 -
Animals : An Open Access Journal From... May 2024The transcriptome complexity and splicing patterns in male and female cattle are ambiguous, presenting a substantial obstacle to genomic selection programs that seek to...
The transcriptome complexity and splicing patterns in male and female cattle are ambiguous, presenting a substantial obstacle to genomic selection programs that seek to improve productivity, disease resistance, and reproduction in cattle. A comparative transcriptomic analysis using Oxford Nanopore Technologies (ONT) was conducted in bovine testes (TESTs), ovaries (OVAs), muscles (MUSCs), and livers (LIVs). An average of 5,144,769 full-length reads were obtained from each sample. The TESTs were found to have the greatest number of alternative polyadenylation (APA) events involved in processes such as sperm flagellum development and fertilization in male reproduction. In total, 438 differentially expressed transcripts (DETs) were identified in the LIVs in a comparison of females vs. males, and 214 DETs were identified in the MUSCs between females and males. Additionally, 14,735, 36,347, and 33,885 DETs were detected in MUSC vs. LIV, MUSC vs. TEST, and OVA vs. TEST comparisons, respectively, revealing the complexity of the TEST. Gene Set Enrichment Analysis (GSEA) showed that these DETs were mainly involved in the "spermatogenesis", "flagellated sperm motility", "spermatid development", "reproduction", "reproductive process", and "microtubule-based movement" KEGG pathways. Additional studies are necessary to further characterize the transcriptome in different cell types, developmental stages, and physiological conditions in bovines and ascertain the functions of the novel transcripts.
PubMed: 38891695
DOI: 10.3390/ani14111646 -
Animals : An Open Access Journal From... May 2024Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the...
Upon encountering a virus, fish initiate an innate immune response, guided by IFNs. Foxo3 plays a part in the body's immune response; however, its specific role in the IFN-guided immune response in fish is yet to be clarified. In this study, we characterized in Japanese medaka () and examined its role in the IFN-dependent immune response upon infection with the RGNNV. The results show that the coding region of the medaka gene is 2007 base pairs long, encoding 668 amino acids, and possesses a typical forkhead protein family structural domain. The product of this gene shares high homology with foxo3 in other fish species and is widely expressed, especially in the brain, eyes, testes, and heart. Upon RGNNV infection, mutant larvae showed a lower mortality rate, and adults exhibited a significant reduction in virus replication. Moreover, the absence of expression led to an increase in the expression of , and a decrease in the expression of other IFN-related genes such as and , implying that may function as a negative regulator in the antiviral signaling pathway. These findings provide crucial insights for disease-resistant breeding in the aquaculture industry.
PubMed: 38891634
DOI: 10.3390/ani14111587 -
Cells Jun 2024Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator...
Ferroptosis hallmarked by lipid peroxidation and iron homeostasis imbalance is involved in the occurrence and development of various diseases. The plant growth regulator chlormequat chloride (CCC) can contribute to the causality and exacerbation of reproductive disorders. However, the mechanism by which CCC may cause Leydig cell attenuation remains poorly understood. In this study, TM3 Leydig cells were used to investigate the inhibitory effect of CCC on cell growth and its possible mechanism. The results showed that CCC caused apoptosis, pyroptosis, ferroptosis and necroinflammation in TM3 cells. By comparing the effects of ferroptosis inhibitor Ferrostatin-1 (Fer-1) and pan-Caspase inhibitor Z-VAD-FMK (ZVF) on lipid peroxidation and Caspase-mediated regulated cell death (RCD), we found that Fer-1 was better at rescuing the growth of TM3 cells than ZVF. Although ZVF reduced mitochondrial ROS level and inhibited the activation of Caspase3 and Caspase1, it could not significantly ameliorate lipid peroxidation and the levels of IL-1β and HMGB1 like Fer-1. Therefore, ferroptosis might be a key non apoptotic RCD mode responsible for CCC-driven inflammation, leading to weakened viability and proliferation of TM3 cells. In addition, overexpression of ferritin light chain (FTL) promoted the resistance of TM3 cells to CCC-induced ferroptosis-mediated inflammation and to some extent improved the inhibition of viability and proliferation. Altogether, ferroptosis-initiated inflammation might play a key role in CCC-impaired TM3 cell growth.
Topics: Ferroptosis; Animals; Male; Mice; Leydig Cells; Inflammation; Cell Proliferation; Lipid Peroxidation; Reactive Oxygen Species; Cell Line; Apoptosis; Mitochondria; Amino Acid Chloromethyl Ketones; Cyclohexylamines; Phenylenediamines
PubMed: 38891111
DOI: 10.3390/cells13110979 -
Journal of Assisted Reproduction and... Jun 2024To identify the sperm preparation procedure that selects the best sperm population for medically assisted reproduction.
PURPOSE
To identify the sperm preparation procedure that selects the best sperm population for medically assisted reproduction.
METHODS
Prospective observational study comparing the effect of four different sperm selection procedures on various semen parameters. Unused raw semen after routine diagnostic analysis was split in four fractions and processed by four different methods: (1) density gradient centrifugation (DGC), (2) sperm wash (SW), (3) DGC followed by magnetic activated cell sorting (MACS), and (4) using a sperm separation device (SSD). Each fraction was analyzed for progressive motility, morphology, acrosome index (AI), and DNA fragmentation index (DFI).
RESULTS
With DGC as standard of care in intraclass correlation coefficient analysis, only SSD was in strong disagreement regarding progressive motility and DFI [0.26, 95%CI (- 0.2, 0.58), and 0.17, 95%CI (- 0.19, 0.45), respectively]. When controlling for abstinence duration, DFI was significantly lower after both MACS and SSD compared to DGC [- 0.27%, 95%CI (- 0.47, - 0.06), p = 0.01, and - 0.6%, 95%CI (- 0.80, - 0.41), p < 0.001, respectively]. Further comparisons between SSD and MACS indicate significantly less apoptotic cells [Median (IQR) 4 (5), 95%CI (4.1, - 6.8) vs Median (IQR) 5 (8), 95%CI (4.9, - 9.2), p < 0.001, respectively] and dead cells [Median (IQR) 9.5 (23.3), 95%CI (13.2, - 22.4) vs Median (IQR) 22 (28), 95%CI (23.1, - 36.8), p < 0.001, respectively] in the SSD group.
CONCLUSION
The selection of a population of highly motile spermatozoa with less damaged DNA from unprocessed semen is ideally performed with SSD. Question remains whether this method improves the embryological outcomes in the IVF laboratory.
PubMed: 38890266
DOI: 10.1007/s10815-024-03168-9 -
Early Human Development Jun 2024It is thought that digit ratios (2D:4D) are a correlate of 1st trimester maternal and foetal sex steroids. Here we consider the relationship of 2D:4D to the former.
BACKGROUND
It is thought that digit ratios (2D:4D) are a correlate of 1st trimester maternal and foetal sex steroids. Here we consider the relationship of 2D:4D to the former.
METHOD
Digit lengths were directly measured with a calliper at infant age 13 months. Measures of T and E were obtained from mother's blood at 6-8 weeks, 10-11 weeks and 1st trimester means were calculated.
RESULTS
There were 69 mother-infant pairs (33 boys). Sex differences in 2D:4D (boys
boys) were found. For mothers of girls: there were negative relationships between 2D:4D and T at 6-8 weeks, 10-11 weeks and 1st trimester means. For infants: girls showed more correlations between 2D:4D and hormones than boys. For boys, there was one positive association between 2D:4D and E and two positive associations for E/T. For girls, 2D:4D was negatively related to T (four correlations) and positively related to E/T (four correlations). Considering associations in the total sample and controlling for sex, at 6-8 weeks right and left 2D:4D were positively related to E. At 10-11 weeks, right and left 2D:4D were negatively related to T. For 1st trimester means, 2D:4D's were positively related to E (right and left) and negatively related to T (right). CONCLUSION
Infant 2D:4D was correlated with first trimester maternal sex steroids, particularly at 10-11 weeks. The correlations were negative for T, and positive for E and E/T with weaker effects for male infants. The latter pattern may arise because in boys T produced by foetal testes masks the effect of maternal T.
PubMed: 38889565
DOI: 10.1016/j.earlhumdev.2024.106067 -
Proceedings of the National Academy of... Jun 2024Germ cells are regulated by local microenvironments (niches), which secrete instructive cues. Conserved developmental signaling molecules act as niche-derived regulatory...
Germ cells are regulated by local microenvironments (niches), which secrete instructive cues. Conserved developmental signaling molecules act as niche-derived regulatory factors, yet other types of niche signals remain to be identified. Single-cell RNA-sequencing of sexual planarians revealed niche cells expressing a nonribosomal peptide synthetase (). Inhibiting led to loss of female reproductive organs and testis hyperplasia. Mass spectrometry detected the dipeptide β-alanyl-tryptamine (BATT), which is associated with reproductive system development and requires and a monoamine-transmitter-synthetic enzyme Aromatic L-amino acid decarboxylase (AADC) for its production. Exogenous BATT rescued the reproductive defects after or inhibition, restoring fertility. Thus, a nonribosomal, monoamine-derived peptide provided by niche cells acts as a critical signal to trigger planarian reproductive development. These findings reveal an unexpected function for monoamines in niche-germ cell signaling. Furthermore, given the recently reported role for BATT as a male-derived factor required for reproductive maturation of female schistosomes, these results have important implications for the evolution of parasitic flatworms and suggest a potential role for nonribosomal peptides as signaling molecules in other organisms.
Topics: Animals; Planarians; Female; Male; Peptide Synthases; Sexual Development; Peptides; Reproduction; Signal Transduction
PubMed: 38889152
DOI: 10.1073/pnas.2321349121 -
Reproduction in Domestic Animals =... Jun 2024Dimensions of linear type traits facilitate selection of livestock for breeding and rearing. To date, use of linear type traits for selection of breeding bulls is highly...
Dimensions of linear type traits facilitate selection of livestock for breeding and rearing. To date, use of linear type traits for selection of breeding bulls is highly concentric to scrotal circumference (SC), with probable overlook to other important traits. Present study reported the importance of various gonadal linear type traits on spermatozoa production, age-related changes in gonadal linear type traits of bulls and predictive ability of these traits on bulls' reproductive potentials. Among all gonadal traits, testicular density (TD), scrotal volume (SV), paired testicular weight (PWT) and SC were found most important predictor variables in order, which can discriminate between good/poor breeding bulls, that is, produced frozen semen doses (FSD) or not. Dimensions of gonadal traits increased significantly up to 36 months age and thereafter, development became slow and negligible. In contrast, TD decreased by 30%, 51%, 64%, 68% and 71% at 12, 24, 36, 48 and >49 months age, respectively, from its base value at 6 months. Bulls of lower TD (≤0.88 g/cm) had significantly higher ejaculate volume (+9%), sperm motility, sperm concentration (+100 million/mL) and sperm output (+26%)/ejaculate as compared to bulls of higher TD (>0.88 g/cm). Discriminant function was developed using TD, SV, PWT and SC to identify bulls of superior reproductive potentials. It was concluded that among the investigated traits, TD was the strongest to discriminate between FSD and Non-FSD bulls. Therefore, our findings suggested that TD could be more potential trait than SC for dairy bulls' breeding soundness evaluation and assessment of reproductive ability.
Topics: Animals; Male; Cattle; Testis; Scrotum; Breeding; Reproduction; Sperm Motility; Semen Analysis; Organ Size; Spermatozoa; Sperm Count; Semen Preservation; Dairying
PubMed: 38888049
DOI: 10.1111/rda.14641