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Cells Jun 2024gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the...
gene loss-of-function mutation leads to Primary Ciliary Dyskinesia (PCD), a disease caused by motile cilia dysfunction. Previously, we demonstrated that knockout of the gene in mice replicates several features of PCD, such as hydrocephalus, defects in left-right body symmetry, and male infertility, with a complete absence of sperm in the reproductive tract. The majority of knockout animals die before sexual maturation due to severe hydrocephalus and failure to thrive, which precludes fertility studies. Here, we performed the expression analysis of the gene during gonad development and in adult testes. We showed that starts its expression during the first wave of spermatogenesis, specifically at the meiotic stage, and that its expression is restricted to the germ cells in the adult testes, suggesting that plays a role in spermatozoa formation. Subsequently, we conditionally deleted the gene in adult males and demonstrated that even partial ablation of the gene leads to asthenoteratozoospermia with multiple morphological abnormalities of sperm flagella (MMAF) in mice. The analysis of the seminiferous tubules in -deficient mice revealed defects in spermatogenesis with accumulation of seminiferous tubules at the spermiogenesis and spermiation phases. Furthermore, analysis of fertility in heterozygous knockout mice revealed a reduction in sperm count and motility as well as abnormal sperm morphology. Additionally, males exhibited a shorter fertile lifespan. Overall, these results suggest the important role of and gene dosage in male fertility. These findings may have an impact on the genetic and fertility counseling practice of PCD patients carrying loss-of-function mutations.
Topics: Animals; Male; Spermatogenesis; Fertility; Mice; Spermatozoa; Mice, Knockout; Testis; Infertility, Male; Mice, Inbred C57BL
PubMed: 38920681
DOI: 10.3390/cells13121053 -
Current Medicinal Chemistry Jun 2024Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the...
Methamphetamine (METH), an amphetamine-type stimulant, has been extensively abused globally in the past decades. METH use causes great harm to the major systems of the human body. Specifically, METH has a negative impact on the hypothalamic- pituitary-testicular axis, testicular structure, sperm function, ovarian folliculogenesis, oocyte quality, embryo development, and newborns. However, the mechanisms underlying these toxic effects have not yet been fully described. This study reviews the evidence concerning the impact of METH on male and female reproduction in the context of the testis, sperm, ovaries, oocytes, reproductive hormones, embryo development, and newborns, discussing the potential pathophysiological mechanisms in the reproductive toxicity induced by METH.
PubMed: 38920076
DOI: 10.2174/0109298673299759240603091021 -
Toxicology Mechanisms and Methods Jun 2024This study aimed to investigate the effects of copper (CuSO) and zinc (ZnSO) overload on male reproductive toxicity and the potential of a polysaccharide extracted from...
This study aimed to investigate the effects of copper (CuSO) and zinc (ZnSO) overload on male reproductive toxicity and the potential of a polysaccharide extracted from green alga (PS) in mitigating their toxicities. Adult male mice strain of 25 ± 2 g of weight was subdivided into eight groups. Group 1 served as control; group 2 received PS (200 mg/kg), and groups 3 and 4 received intraperitoneally zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), respectively. Group 5 received both zinc (60 mg/kg b.w) and copper (33 mg/kg b.w), group 6 received zinc (60 mg/kg b.w) associated with PS (200 mg/kg), group 7 received copper (33 mg/kg b.w) associated with PS (200 mg/kg), and group 8 received zinc (60 mg/kg b.w) and copper (33 mg/kg b.w) associated with PS (200 mg/kg). Results suggested that ZnSO and CuSO significantly decreased the functional sperm parameters. Furthermore, extended exposure to these elements increased oxidative stress biomarkers, including malondialdehyde (MDA) as a measure of lipid peroxidation and advanced oxidation protein products (AOPP) indicating protein oxidative damage. This process also reduces the activity of antioxidant enzymes such as glutathione (GSH) and glutathione peroxidase (GPx), which neutralize and catalyze free radicals. Histopathological changes in mice testis were also studied. However, the co-treatments with PS significantly reduced these effects and promoted the reproductive parameters in male mice. In conclusion, PS exhibited protective effects against zinc and copper-induced reproductive toxicity, making it a potential adjuvant treatment for testicular toxicity.
PubMed: 38918930
DOI: 10.1080/15376516.2024.2361070 -
World Journal of Urology Jun 2024The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed...
BACKGROUND
The last decades revealed new scientific knowledge regarding the fertility and potential malignancy of undescended testis AQ2(UDT). Accordingly, many guidelines changed their recommendation concerning timing of therapy, with the goal of an earlier time of surgery.
METHODS
We analyzed the number of new diagnosis and performed surgeries in predefined age groups provided by the obligatory annual reports of German hospitals in the reimbursement.INFO"-tool between 2006 and 2020.
RESULTS
Overall, 124,741 cases were analyzed. We showed a slight increase in performed surgeries in the first year by 2% per year with a main increase till 2011, a constant number of surgeries between first and 4th year and a decrease of surgeries between 5 and 14th year of living with a main decrease till 2009 by 3% per year.
CONCLUSION
Even if our results illustrate an increasing adaption of the guideline's recommendation, there is still a significant number of patients who receive later treatment. More research about the reasons and circumstances for the latter is needed.
Topics: Cryptorchidism; Humans; Male; Germany; Orchiopexy; Practice Guidelines as Topic; Child; Adolescent; Child, Preschool; Infant; Time Factors; Young Adult; Adult
PubMed: 38918219
DOI: 10.1007/s00345-024-05095-x -
Behavioural Processes Jun 2024Exaggerated sexual traits, such as ornaments and courtship displays, are crucial for mate acquisition in many species and are often subject to directional runaway...
Exaggerated sexual traits, such as ornaments and courtship displays, are crucial for mate acquisition in many species and are often subject to directional runaway selection. However, in the face of high predation risk, natural selection can result in a reduction of conspicuous precopulatory displays to avoid detection by potential predators. Sexual selection may then favour increased investment in inconspicuous postcopulatory traits. Here, we investigated the transgenerational effects of predation on precopulatory male courtship and postcopulatory sexual traits (testes size, sperm length) in a dung fly, Sepsis punctum (Sepsidae). Behavioural assays prior to selection document a marked decrease in male courtship displays in the presence of a predator, the Asian Ant Mantis (Odontomantis planiceps). However, after ten generations of experimental evolution, flies exhibited a marked increase in courtship, both in the absence and presence of a predator. Additionally, under sustained predation pressure, male and female body size decreased but male postcopulatory traits were not significantly affected. These results suggest that precopulatory courtship can be under strong sexual selection even in the face of predation pressure. Larger flies were more susceptible to predation, and there could be canalisation of postcopulatory traits that are crucial for fertilisation.
PubMed: 38917938
DOI: 10.1016/j.beproc.2024.105073 -
General and Comparative Endocrinology Jun 2024Recombinant gonadotropins, follicle stimulating (rFsh) and luteinizing hormone (rLh), offer the potential to induce gametogenesis in prepubertal fish. This study aimed...
Recombinant gonadotropins, follicle stimulating (rFsh) and luteinizing hormone (rLh), offer the potential to induce gametogenesis in prepubertal fish. This study aimed to determine the in vivo effect of the administration of Argyrosomus regius rFsh and rLh on the reproductive development of prepubertal meagre juveniles at the initial stages of sexual differentiation. Juvenile meagre, 9-months old with mean weight of 219 ± 3.9 g (mean ± SEM) were randomly distributed into nine groups (n = 8 per group). Experimental groups were treated weekly with an acute injection of either rFsh or rLh. Control groups were injected with saline solution. In a 3-week experiment, different groups were administered with different doses 6, 12 or 18 µg kg of rFsh or rLh or saline solution. In a 6-week experiment a group was administered with 12 µg kg of rFsh and a second group with saline solution. The fish were held in a single 10 m tank with natural photoperiod (Feb. - March) and temperature 16.1 ± 0.4 °C. At the start of the experiment (n = 8) and at the end of the 3-week experiment, fish were blood sampled and sacrificed. Blood was analysed for 17β-estradiol (E2) and 11-ketotestosterone (11-KT). Gonads and liver were dissected and weighed. Gonads were fixed in Bouińs solution and processed for histological analysis. Juvenile meagre at the start of the experiment were in the initial stages of sexual differentiation, indicated by the presence of the ovarian cavity or testes duct that was surrounded by undifferentiated embryonic germ stem cells and somatic cells. At the end of the 3-week experiment, there was no significant difference in gonadosomatic index (GSI) amongst control (initial and saline treated) and the experimental groups. After three weeks of application of rFsh, rLh or saline all fish presented a similar gonadal structure as at the start of the experiment. However, the incidence of sporadic developing germ cells (principally spermatogonia, spermatocytes, spermatids, but also perinucleolar stage oocytes) generally increased in rGth treated meagre. A mean of 44 % of meagre treated with rFsh or rLh presented sporadic isolated developing germ cells, mainly male cells. Plasma steroid levels of E2 decreased significantly from the start of the experiments to the end. At the end of the experiments there were no differences in plasma E2 amongst Control fish and rGth treated fish. Plasma 11-KT showed no change from the start of the experiment to week 3. However, a significant increase was observed in a proportion of the rFsh group after six weeks of treatment compared to the start of the experiment and the saline control group on week 6. The application of rFsh or rLh to meagre at the initial stages of sex differentiation did not stimulate steroid production until week six (11-KT) and had a limited, but evident effect on the development of sporadic isolated germ cells. However, we conclude that rGth, rFsh or rLh did not stimulate large developmental changes in sexually undifferentiated meagre gonads.
PubMed: 38917936
DOI: 10.1016/j.ygcen.2024.114576 -
International Journal of Surgery Case... Jun 2024Fournier's gangrene (FG) in neonates is less common than in adults, but this case can lead to a poor prognosis. FG is a disease of the genital, perianal, and perineal...
INTRODUCTION
Fournier's gangrene (FG) in neonates is less common than in adults, but this case can lead to a poor prognosis. FG is a disease of the genital, perianal, and perineal areas characterized by necrotizing infections. Here, we report a case of a 24-day-old male infant diagnosed with Fournier's gangrene involving the scrotum.
CASE PRESENTATION
The patient presented with scrotal swelling, fever, erythema, and insect bites on the penile tip that had gradually extended to the proximal area and bilateral scrotum. On physical examination, indurated grayish and blackish-brown scrotal skin with sharp distinction from the surrounding normal skin, erythema, purulence, ulceration, and necrotic tissue were observed. Abdominal X-ray and scrotal ultrasonography revealed gaseous distension of the scrotal region, free fluid on bilateral testes, and enlargement of bilateral testicles. Immediate surgical debridement, along with broad-spectrum antibiotics, was initiated, and a microbiological culture identified the presence of Pseudomonas aeruginosa. The patient demonstrated the completed healing of the surgical wound after thirty days of surgical intervention.
DISCUSSION
Fournier's gangrene in neonates is a sporadic case. Our patient presented with multiple predisposing factors, including insect bites and poor hygiene, underscoring the need for heightened clinical suspicion in vulnerable populations. Prompt recognition and intervention are critical, given the rapid progression of FG.
CONCLUSION
This case underscores the importance of timely diagnosis and early initiation of surgical and medical interventions in neonatal Fournier's gangrene, particularly in cases involving the scrotum.
PubMed: 38917701
DOI: 10.1016/j.ijscr.2024.109861 -
Biochemical and Biophysical Research... Jun 2024The testis-specific histone variant H3T plays a crucial role in chromatin reorganization during spermatogenesis by destabilizing nucleosomes. However, the structure...
The testis-specific histone variant H3T plays a crucial role in chromatin reorganization during spermatogenesis by destabilizing nucleosomes. However, the structure basis for the nucleosome instability driven by H3T is not fully understand. In this study, we determinate the crystal structure of H3T-H4 in complex with histone chaperone ASF1a at 2.8 Å resolution. Our findings reveal that H3T-H4 binds ASF1a similarly to the conventional H3.1-H4 complex. However, significant structural differences are observed in the H3 α1 helix, the N- and C-terminal region of α2, and N-terminal region of L2. These differences are driven by H3T-specific residues, particularly Val111. Unlike the smaller Ala111 in H3.1, we find that bulkier residue Val111 fits well within the ASF1-H3T-H4 complex, but is difficult to arrange in nucleosome structure. Given that H3.1-Ala111/H3T-Val111 is located at the DNA binding and tetramerization interface of H3-H4, it is likely that Ala111Val substitution will lead to the instability of the corresponding area in nucleosome, contributing to instability of H3T-containing nucleosome. These structural findings may elucidate the role of H3T in chromatin reorganization during spermatogenesis.
PubMed: 38917618
DOI: 10.1016/j.bbrc.2024.150307 -
Poultry Science May 2024Sperm mobility (SM) is an objective index for measuring sperm motility; however, the mechanisms underlying its regulation in geese remain unclear. The present study...
Sperm mobility (SM) is an objective index for measuring sperm motility; however, the mechanisms underlying its regulation in geese remain unclear. The present study sought to elucidate the genetic mechanism underlying SM traits in Zi geese (Anser cygnoides L.). To this end, three successive experiments were performed. In Experiment I, SM was determined in 40 ganders; the 3 ganders with the highest mobility and three with the lowest mobility were assigned to the high and low sperm mobility rank (SMR) groups, respectively. In Experiment II, the differences in fertility between the two SMR groups were assessed within two breeding flocks comprising the selected six ganders from Experiment I and 30 females (each flock had 3 ganders and 15 females). In Experiment III, the testes of the 6 ganders were harvested for histological observation and whole-transcriptome sequencing. Results revealed better fertility, well-developed seminiferous tubules, and abundant mature sperm in the high-SMR-flock compared to those of the low-SMR-flock (89 vs. 81%) (P < 0.05). Differential expression (DE) analysis identified 76 mRNAs, 344 lncRNAs, and 17 miRNAs between the SMR groups, with LOC106049708, XPNPEP3, GNB3, ADCY8, PRKAG3, oha-miR-182-5p, and ocu-miR-10b-5p identified as key mRNAs and miRNAs contributing to SM. Enrichment analysis implicated these DE RNAs in pathways related to ATP binding, cell metabolism, apelin signaling, Wnt signaling, and Adherens junctions. Additionally, competing endogenous RNA (ceRNA) networks comprising 9 DE mRNAs, 17 DE miRNAs, and 169 DE lncRNAs were constructed. Two ceRNA network pathways (LOC106049708-oha-miR-182-5p-MSTRG.2479.6 and PRKAG3-ocu-miR-10b-5p-MSTRG.9047.14) were identified as key regulators of SM in geese. These findings offer crucial insights into the identification of key genes and ceRNA pathways influencing sperm mobility in geese.
PubMed: 38917609
DOI: 10.1016/j.psj.2024.103895 -
Poultry Science Apr 2024Magang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in...
Magang geese are typical short-day breeders whose reproductive behaviors are significantly influenced by photoperiod. Exposure to a long-day photoperiod results in testicular regression and spermatogenesis arrest in Magang geese. To investigate the epigenetic influence of DNA methylation on the seasonal testicular regression in Magang geese, we conducted whole-genome bisulfite sequencing and transcriptome sequencing of testes across 3 reproductive phases during a long-day photoperiod. A total of 250,326 differentially methylated regions (DMR) were identified among the 3 comparison groups, with a significant number showing hypermethylation, especially in intronic regions of the genome. Integrating bisulfite sequencing with transcriptome sequencing data revealed that DMR-associated genes tend to be differentially expressed in the testes, highlighting a potential regulatory role for DNA methylation in gene expression. Furthermore, there was a significant negative correlation between changes in the methylation of CG DMRs and changes in the expression of their associated genes in the testes. A total of 3,359 DMR-associated differentially expressed genes (DEG) were identified; functional enrichment analyses revealed that motor proteins, MAPK signaling pathway, ECM-receptor interaction, phagosome, TGF-beta signaling pathway, and calcium signaling might contribute to the testicular regression process. GSEA revealed that the significantly enriched activated hallmark gene set was associated with apoptosis and estrogen response during testicular regression, while the repressed hallmark gene set was involved in spermatogenesis. Our study also revealed that methylation changes significantly impacted the expression level of vitamin A metabolism-related genes during testicular degeneration, with hypermethylation of STRA6 and increased calmodulin levels indicating vitamin A efflux during the testicular regression. These findings were corroborated by pyrosequencing and real-time qPCR, which revealed that the vitamin A metabolic pathway plays a pivotal role in testicular degeneration under long-day conditions. Additionally, metabolomics analysis revealed an insufficiency of vitamin A and an abnormally high level of oxysterols accumulated in the testes during testicular regression. In conclusion, our study demonstrated that testicular degeneration in Magang geese induced by a long-day photoperiod is linked to vitamin A homeostasis disruption, which manifests as the hypermethylation status of STRA6, vitamin A efflux, and a high level of oxysterol accumulation. These findings offer new insights into the effects of DNA methylation on the seasonal testicular regression that occurs during long-day photoperiods in Magang geese.
PubMed: 38917605
DOI: 10.1016/j.psj.2024.103769