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Scientific Reports Nov 2023There is little information on the effects of exposure to light emitting diode (LED) illumination on the welfare of laboratory animals. Nesfatin-1, a satiety-regulation...
There is little information on the effects of exposure to light emitting diode (LED) illumination on the welfare of laboratory animals. Nesfatin-1, a satiety-regulation peptide present in various tissues, is found in the central nervous system and participates in the stress response. The present study investigated whether exposure to blue and white LED lights for 14 weeks affected growth and reproductive, biochemical and histopathological parameters in male Sprague Dawley (SD) rats as well as whether subcutaneous (SC) injection of nesfatin-1 (0.5 mg/kg bodyweight) in the last two weeks of the experimental period alleviated these effects. Forty male SD rats (21 days of age) were randomly allotted to 6 groups. The animals were exposed to routine fluorescent light (the control [C] and control + sesame oil [CS] groups) or blue/white LEDs (the blue-LED and white-LED groups), accompanied by nesfatin-1 administration (the blue-LED-N1 and white-LED-N1 groups). White-LED rats had significantly higher testis weights (p < 0.05) than control and blue-LED rats. Serum melatonin levels were significantly lower in blue-LED rats, but nesfatin-1 injection rescued melatonin levels in blue-LED-N1 rats (p < 0.05). Blue-LED rats showed the highest serum nesfatin-1 levels, but nesfatin-1 injection decreased nesfatin-1 levels in blue-LED-N1 rats (p < 0.0001). Blue-LED rats showed a significant reduction in sperm motility compared to the other groups (p < 0.0001). White and blue LED exposure caused significant negative histopathological changes in the testes, but nesfatin-1 administration reduced edema in the intertubular spaces, hyperemia in the interstitial cells, degeneration of spermatocytes and thinning of the tubular wall in the testicular tissues; these restorative effects were larger in blue-LED-N1 rats than white-LED-N1 rats. Blue and white LED exposures had negative effects on melatonin levels, testis weights and tissue health. Nesfatin-1 alleviated some of the negative effects of LED lighting.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Melatonin; Reproductive Health; Sperm Motility; Testis
PubMed: 37968298
DOI: 10.1038/s41598-023-46137-5 -
JBRA Assisted Reproduction Feb 2024Penconazole is used in agriculture and human and veterinary medicine applications. It has been included in the acute toxicity hazard category by the WHO. This study...
OBJECTIVE
Penconazole is used in agriculture and human and veterinary medicine applications. It has been included in the acute toxicity hazard category by the WHO. This study examines the protective effect of selenium and vitamin C on the fertility of male rats given penconazole.
METHODS
Nine groups of rats were given penconazole at concentrations of 50 and 75 mg/ml and selenium and vitamin C at concentrations of 0.5 and 100 mg/ml, respectively. Serum levels of LH and FSH were measured with ELISA kits; β-actin, GPX4, AQP7, PRM2, and BAX gene expression was evaluated with real-time PCR performed on the left testis of each rat.
RESULTS
LH, FSH, and testosterone levels were lower in the groups given penconazole (50 and 75 mg/kg). Histopathology showed that the groups given penconazole had the lowest number of spermatogonia and primary spermatocytes; these numbers were greater in the groups receiving penconazole together with selenium or vitamin C; and the highest counts were observed in separate groups given Se and vitamin C. GPX4, AQP7, PRM2 and BAX gene expression in the groups receiving penconazole was different from controls and was modulated by treatment with selenium or vitamin C.
CONCLUSIONS
This study showed that antioxidant compounds have a strengthening effect on the reproductive system and can mitigate the destructive effects of chemical fungicides.
Topics: Humans; Rats; Male; Animals; Ascorbic Acid; Selenium; bcl-2-Associated X Protein; Fertility; Follicle Stimulating Hormone; Triazoles
PubMed: 37962947
DOI: 10.5935/1518-0557.20230042 -
Toxicological Sciences : An Official... Nov 2023The blood-testis barrier (BTB) is constituted by tight junctions between adjacent Sertoli cells (SC) that create a specialized adluminal microenvironment to foster the...
The blood-testis barrier (BTB) is constituted by tight junctions between adjacent Sertoli cells (SC) that create a specialized adluminal microenvironment to foster the development of spermatocytes and spermatids. The BTB is a well-studied target of numerous environmental toxicants, including di-(2-ethylhexyl) phthalate (DEHP), a compound widely used in various consumer products. MEHP is the active toxic metabolite of DEHP that has long been recognized in postnatal rodents to disrupt SC function. This study evaluates the impact of MEHP on the integrity of the BTB in both pubertal and adult rats and the signal transduction pathways known to be involved in the disruption of the BTB. Treatment of prepubertal rats with 700 mg/kg MEHP for 24 hours functionally disrupted the BTB integrity. A similar treatment of adult rats with MEHP did not disrupt the integrity of the BTB. The observed disruption of the BTB integrity in the MEHP-treated prepubertal rats occurred concomitantly with a decreased expression and mislocalization of both the ZO1 and occludin tight junction-associated proteins, as well as sloughing of spermatocytes and spermatids. At this same time, MEHP treatment induced a transient surge of p44/42 mitogen-activated protein kinase (MAPK) pathway. Interestingly, after a recovery period of 5 weeks, the BTB recovered and was functionally intact. This is the first report to indicate that acute MEHP exposure of prepubertal rats, but not adult rats, disrupts the functional integrity of the BTB and that this effect on the BTB is reversible.
PubMed: 37941498
DOI: 10.1093/toxsci/kfad116 -
Ecotoxicology and Environmental Safety Nov 2023Nanoplastics (NPs) and Microplastics (MPs) pollution has become a severe threat to the planet and is a growing concern. However, their effects on male reproductive...
Nanoplastics (NPs) and Microplastics (MPs) pollution has become a severe threat to the planet and is a growing concern. However, their effects on male reproductive toxicity remain poorly understood. In this study, a series of morphological analyses were completed to explore the influence of NPs and MPs exposure on the testis in mice. After 12-weeks exposure, although both NPs and MPs exposure can lead to reproductive toxicity, compared with NPs exposure, exposure to MPs leads to a more significant increase in reproductive toxicity dependent on some particle size. Moreover, increased reproductive toxicities, including increased spermatogenesis disorders, and sperm physiological abnormality, oxidative stress, testis inflammation was more associated with MPs group than NPs group. Ultra-pathological structure observed by transmission electron microscopy indicated that both NPs and MPs have different effects on spermatogonia, spermatocytes and Sertoli cells. Exposure to MPs resulted in decreased Sertoli cell numbers and reduced Leydig cell area, and showed no effects on differentiation of Leydig cells by the expression level of the Insulin-Like factor 3 (INSL3) in Leydig cells. Transcriptomic sequencing analysis provided valuable insights into the differential effects of NPs and MPs on cellular processes. Specifically, our findings demonstrated that NPs were predominantly involved in the regulation of steroid biosynthesis, whereas MPs primarily influenced amino acid metabolism. This study demonstrates the effect of adult-stage reproductive toxicity in mice after exposure to NPs and MPs, which will deep the understanding of the NPs and MPs induced toxicity.
Topics: Male; Animals; Mice; Testis; Microplastics; Plastics; Semen; Spermatozoa
PubMed: 37939553
DOI: 10.1016/j.ecoenv.2023.115618 -
AJP Reports Jul 2023Down syndrome (DS, trisomy 21) with an extra copy of chromosome 21 is one of the most common aneuploidies in humans. Jacobs syndrome or XYY syndrome (trisomy XYY) with...
Down syndrome (DS, trisomy 21) with an extra copy of chromosome 21 is one of the most common aneuploidies in humans. Jacobs syndrome or XYY syndrome (trisomy XYY) with an extra copy of sex chromosome Y is a rare sex chromosome trisomy in males. Double aneuploidy (DA) with an extra copy of chromosome 21 and sex chromosome Y is an extremely rare occurrence. Most trisomy 21 results from nondisjunction during maternal oocyte meiosis-I, whereas trisomy XYY is results from nondisjunction during paternal spermatocyte meiosis-I. We present a case of natural conception premature newborn of 30.4 weeks gestational age who had a DS facial phenotype with extensive syndactyly on both hands and feet. Other multisystem congenital anomalies were discovered, including mal-aligned perimembranous ventricular septal defect, bicuspid aortic valve, Dandy-Walker malformation's tetra-ventriculomegaly, and a rare complete tracheal rings deformity (CTRD) with trachea stenosis. Prenatal amniocentesis and postnatal chromosomal karyotyping analysis detected 48, XYY, + 21 nontranslocation trisomy 21, and free-lying Y chromosome without translocation. The existence of DA is rarely reported in literature reviews. In this review, we will discuss the characteristics of DS and Jacobs syndrome as well as the associated multiorgan malformation including the rare lethal CTRD.
PubMed: 37937269
DOI: 10.1055/s-0043-1774728 -
Zoological Research Nov 2023Tree shrews ( ) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based...
Tree shrews ( ) share a close relationship to primates and have been widely used in biomedical research. We previously established a spermatogonial stem cell (SSC)-based gene editing platform to generate transgenic tree shrews. However, the influences of long-term expansion on tree shrew SSC spermatogenesis potential remain unclear. Here, we examined the spermatogenesis potential of tree shrew SSCs cultured across different passages. We found that SSCs lost spermatogenesis ability after long-term expansion (>50 passages), as indicated by the failure to colonize the seminiferous epithelium and generate donor spermatogonia (SPG)-derived spermatocytes or spermatids marking spermatogenesis. RNA sequencing (RNA-seq) analysis of undifferentiated SPGs across different passages revealed significant gene expression changes after sub-culturing primary SPG lines for more than 40 passages on feeder layers. Specifically, DNA damage response and repair genes (e.g., , , , and ) were down-regulated, whereas genes associated with mitochondrial function (e.g., , , , and ) were up-regulated after expansion. The DNA damage accumulation and mitochondrial dysfunction were experimentally validated in high-passage cells. Supplementation with nicotinamide adenine dinucleotide (NAD ) precursor nicotinamide riboside (NR) exhibited beneficial effects by reducing DNA damage accumulation and mitochondrial dysfunction in SPG elicited by long-term culture. Our research presents a comprehensive analysis of the genetic and physiological attributes critical for the sustained expansion of undifferentiated SSCs in tree shrews and proposes an effective strategy for extended maintenance.
Topics: Male; Animals; Tupaia; Tupaiidae; Shrews; Animals, Genetically Modified; Primates; Stem Cells
PubMed: 37914523
DOI: 10.24272/j.issn.2095-8137.2023.317 -
Frontiers in Cell and Developmental... 2023Recessive mutation of the X-linked gene, (), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3...
Recessive mutation of the X-linked gene, (), causes familial ciliopathy. PIH1D3 deficiency is associated with the defects of dynein arms in cilia, but how PIH1D3 specifically affects the structure and function of dynein arms is not understood yet. To gain insights into the underlying mechanisms of the disease, it is crucial to create a reliable animal model. In humans, rats, and mice, one copy of the gene is located on the X chromosome. Interestingly, mice have an additional, intronless copy of the gene on chromosome 1. To develop an accurate disease model, it is best to manipulate the X-linked gene, which contains essential regulatory sequences within the introns for precise gene expression. This study aimed to develop a tailored rat model for PIH1D3-associated ciliopathy with the ultimate goal of uncovering the intricate molecular mechanisms responsible for ciliary defects in the disease. Novel Pih1d3-knockout (KO) rats were created by using TALEN-mediated non-homologous DNA recombination within fertilized rat eggs and, subsequently, underwent a comprehensive characterization through a battery of behavioral and pathological assays. A series of biochemical and histological analyses were conducted to elucidate the identity of protein partners that interact with PIH1D3, thus shedding light on the intricate molecular mechanisms involved in this context. PIH1D3-KO rats reproduced the cardinal features of ciliopathy including situs inversus, defects in spermatocyte survival and mucociliary clearance, and perinatal hydrocephalus. We revealed the novel function of PIH1D3 in cerebrospinal fluid circulation and elucidated the mechanism by which PIH1D3 deficiency caused communicating hydrocephalus. PIH1D3 interacted with the proteins required for the pre-assembly and uploading of outer (ODA) and inner dynein arms (IDA), regulating the integrity of dynein arm structure and function in cilia. PIH1D3-KO rats faithfully reproduced the cardinal features of ciliopathy associated with PIH1D3 deficiency. PIH1D3 interacted with the proteins responsible for the pre-assembly and uploading of dynein arms in cilia, and its deficiency led to dysfunctional cilia and, thus, to ciliopathy by affecting the pre-assembly and uploading of dynein arms. The resultant rat model is a valuable tool for the mechanistic study of PIH1D3-caused diseases.
PubMed: 37900281
DOI: 10.3389/fcell.2023.1282787 -
Biomedicines Sep 2023Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential...
Diabetes mellitus is a metabolic disease that can cause systemic problems, including testicular dysfunction. Several diabetes medications have demonstrated potential adverse effects on the male reproductive system; however, the effects of saxagliptin and dapagliflozin have not been sufficiently examined. This investigation studied the impacts of saxagliptin and dapagliflozin treatments on the gonads in a male mouse model of diabetes. Testicular disturbances were assessed by sperm DNA damage, diakinesis-metaphase I chromosome examination, and spermiogram analysis. Our results showed more sperm DNA damage, more spermatocyte chromosome aberrations, lower sperm motility/count, and more sperm morphological anomalies in diabetic mice than in the control mice. Dapagliflozin significantly restored all examined measures to the control values in diabetic mice, unlike saxagliptin, which exacerbated the reduction in sperm count and motility. Both drugs significantly restored the gonadal redox imbalances in diabetic mice by decreasing reactive oxygen species accumulation and increasing glutathione levels. In conclusion, our study presents preliminary evidence for the safety and efficacy of dapagliflozin in alleviating testicular abnormalities induced by diabetes, making it a promising candidate drug for patients with diabetes in their reproductive age. As saxagliptin may have negative effects on fertility, its prescription should be avoided in young male diabetic patients.
PubMed: 37893048
DOI: 10.3390/biomedicines11102674 -
Nature Communications Oct 2023The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly...
The formation of RAD51/DMC1 filaments on single-stranded (ss)DNAs essential for homology search and strand exchange in DNA double-strand break (DSB) repair is tightly regulated. FIGNL1 AAA+++ ATPase controls RAD51-mediated recombination in human cells. However, its role in gametogenesis remains unsolved. Here, we characterized a germ line-specific conditional knockout (cKO) mouse of FIGNL1. Fignl1 cKO male mice showed defective chromosome synapsis and impaired meiotic DSB repair with the accumulation of RAD51/DMC1 on meiotic chromosomes, supporting a positive role of FIGNL1 in homologous recombination at a post-assembly stage of RAD51/DMC1 filaments. Fignl1 cKO spermatocytes also accumulate RAD51/DMC1 on chromosomes in pre-meiotic S-phase. These RAD51/DMC1 assemblies are independent of meiotic DSB formation. We also showed that purified FIGNL1 dismantles RAD51 filament on double-stranded (ds)DNA as well as ssDNA. These results suggest an additional role of FIGNL1 in limiting the non-productive assembly of RAD51/DMC1 on native dsDNAs during pre-meiotic S-phase and meiotic prophase I.
Topics: Male; Humans; Animals; Mice; Meiosis; Rad51 Recombinase; DNA-Binding Proteins; ATPases Associated with Diverse Cellular Activities; DNA Breaks, Double-Stranded; Cell Cycle Proteins; Homologous Recombination; DNA; DNA Replication; Microtubule-Associated Proteins; Nuclear Proteins
PubMed: 37891173
DOI: 10.1038/s41467-023-42576-w -
Development (Cambridge, England) Nov 2023During meiosis, germ cell and stage-specific components impose additional layers of regulation on the core cell cycle machinery to set up an extended G2 period termed...
During meiosis, germ cell and stage-specific components impose additional layers of regulation on the core cell cycle machinery to set up an extended G2 period termed meiotic prophase. In Drosophila males, meiotic prophase lasts 3.5 days, during which spermatocytes upregulate over 1800 genes and grow 25-fold. Previous work has shown that the cell cycle regulator Cyclin B (CycB) is subject to translational repression in immature spermatocytes, mediated by the RNA-binding protein Rbp4 and its partner Fest. Here, we show that the spermatocyte-specific protein Lut is required for translational repression of cycB in an 8-h window just before spermatocytes are fully mature. In males mutant for rbp4 or lut, spermatocytes enter and exit meiotic division 6-8 h earlier than in wild type. In addition, spermatocyte-specific isoforms of Syncrip (Syp) are required for expression of CycB protein in mature spermatocytes and normal entry into the meiotic divisions. Lut and Syp interact with Fest independent of RNA. Thus, a set of spermatocyte-specific regulators choreograph the timing of expression of CycB protein during male meiotic prophase.
Topics: Animals; Male; Meiosis; Spermatogenesis; Prophase; Mitosis; Spermatocytes; Drosophila; Cyclin B; Drosophila Proteins
PubMed: 37882771
DOI: 10.1242/dev.201709