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Scientific Reports Jun 2024Advancing healthcare for elderly men requires a deeper understanding of testicular aging processes. In this study, we conducted transcriptomic profiling of 43,323...
Advancing healthcare for elderly men requires a deeper understanding of testicular aging processes. In this study, we conducted transcriptomic profiling of 43,323 testicular single cells from young and old mice, shedding light on 1032 telocytes-an underexplored testicular cell type in previous research. Our study unveiled 916 age-related differentially expressed genes (age-DEGs), with telocytes emerging as the cell type harboring the highest count of age-DEGs. Of particular interest, four genes (Klk1b21, Klk1b22, Klk1b24, Klk1b27) from the Kallikrein family, specifically expressed in Leydig cells, displayed down-regulation in aged testes. Moreover, cell-type-level splicing analyses unveiled 1838 age-related alternative splicing (AS) events. While we confirmed the presence of more age-DEGs in somatic cells compared to germ cells, unexpectedly, more age-related AS events were identified in germ cells. Further experimental validation highlighted 4930555F03Rik, a non-coding RNA gene exhibiting significant age-related AS changes. Our study represents the first age-related single-cell transcriptomic investigation of testicular telocytes and Kallikrein genes in Leydig cells, as well as the first delineation of cell-type-level AS dynamics during testicular aging in mice.
Topics: Animals; Male; Mice; Alternative Splicing; Kallikreins; Testis; Aging; Gene Expression Profiling; Single-Cell Analysis; Transcriptome; Leydig Cells
PubMed: 38926537
DOI: 10.1038/s41598-024-65710-0 -
Scientific Reports Jun 2024Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this...
Based on the auditory periphery and the small head size, Etruscan shrews (Suncus etruscus) approximate ancestral mammalian conditions. The auditory brainstem in this insectivore has not been investigated. Using labelling techniques, we assessed the structures of their superior olivary complex (SOC) and the nuclei of the lateral lemniscus (NLL). There, we identified the position of the major nuclei, their input pattern, transmitter content, expression of calcium binding proteins (CaBPs) and two voltage-gated ion channels. The most prominent SOC structures were the medial nucleus of the trapezoid body (MNTB), the lateral nucleus of the trapezoid body (LNTB), the lateral superior olive (LSO) and the superior paraolivary nucleus (SPN). In the NLL, the ventral (VNLL), a specific ventrolateral VNLL (VNLLvl) cell population, the intermediate (INLL) and dorsal (DNLL) nucleus, as well as the inferior colliculus's central aspect were discerned. INLL and VNLL were clearly separated by the differential distribution of various marker proteins. Most labelled proteins showed expression patterns comparable to rodents. However, SPN neurons were glycinergic and not GABAergic and the overall CaBPs expression was low. Next to the characterisation of the Etruscan shrew's auditory brainstem, our work identifies conserved nuclei and indicates variable structures in a species that approximates ancestral conditions.
Topics: Animals; Shrews; Superior Olivary Complex; Auditory Pathways; Neurons; Inferior Colliculi; Calcium-Binding Proteins; Brain Stem; Male; Olivary Nucleus
PubMed: 38926520
DOI: 10.1038/s41598-024-65451-0 -
Human Reproduction (Oxford, England) Jun 2024Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health...
Maternal exposure to endocrine-disrupting chemicals (EDCs) in human pregnancy is widely considered as an important cause of adverse changes in male reproductive health due to impaired foetal androgen production/action. However, the epidemiological evidence supporting this view is equivocal, except for certain phthalates, notably diethyl hexyl phthalate (DEHP). Maternal phthalate exposure levels associated with adverse reproductive changes in epidemiological studies are several thousand-fold lower than those needed to suppress foetal androgen production in rats, and direct studies using human foetal testis tissue show no effect of high phthalate exposure on androgen production. This conundrum is unexplained and raises fundamental questions. Human DEHP exposure is predominantly via food with highest exposure associated with consumption of a Western style (unhealthy) diet. This diet is also associated with increased exposure to the most common EDCs, whether persistent (chlorinated or fluorinated chemicals) or non-persistent (phthalates, bisphenols) compounds, which are found at highest levels in fatty and processed foods. Consequently, epidemiological studies associating EDC exposure and male reproductive health disorders are confounded by potential dietary effects, and vice versa. A Western diet/lifestyle in young adulthood is also associated with low sperm counts. Disentangling EDC and dietary effects in epidemiological studies is challenging. In pregnancy, a Western diet, EDC exposure, and maternal living in proximity to industrial sites are all associated with impaired foetal growth/development due to placental dysfunction, which predisposes to congenital male reproductive disorders (cryptorchidism, hypospadias). While the latter are considered to reflect impaired foetal androgen production, effects resulting from foetal growth impairment (FGI) are likely indirect. As FGI has numerous life-long health consequences, and is affected by maternal lifestyle, research into the origins of male reproductive disorders should take more account of this. Additionally, potential effects on foetal growth/foetal testis from the increasing use of medications in pregnancy deserves more research attention.
PubMed: 38926156
DOI: 10.1093/humrep/deae143 -
The Urologic Clinics of North America Aug 2024Testicular germ cell tumors are rare genitourinary malignancies, but they represent the most common malignancies in men aged 15 to 30 years. Whereas the initial steps... (Review)
Review
Testicular germ cell tumors are rare genitourinary malignancies, but they represent the most common malignancies in men aged 15 to 30 years. Whereas the initial steps of management such as staging imaging studies, inguinal orchiectomy, and tumor marker can be performed elsewhere, the surgical and cytotoxic therapy needs to be done at reference centers. Regionalization of testis care has been shown to result in superior oncological outcome.
Topics: Testicular Neoplasms; Humans; Male; Neoplasms, Germ Cell and Embryonal; Orchiectomy; Neoplasm Staging
PubMed: 38925744
DOI: 10.1016/j.ucl.2024.03.010 -
Annals of the New York Academy of... Jun 2024Infants born with severe central disorders of the hypothalamic-pituitary-gonadal axis leading to gonadotropin deficiency not only lack pubertal development in... (Review)
Review
Infants born with severe central disorders of the hypothalamic-pituitary-gonadal axis leading to gonadotropin deficiency not only lack pubertal development in adolescence, but also lack infantile mini-puberty. This period of mini-puberty, where infants have gonadotropin and sex steroid concentrations up into the adult range, is vital for future reproductive capacity, particularly in boys. At present, there is no consensus on the diagnosis or management of infants with gonadotropin deficiency due to congenital hypogonadotropic hypogonadism or multiple pituitary hormone deficiency. Case series suggest that gonadotropin treatment in male infants with absent mini-puberty is effective in promoting both testicular descent in those with undescended testes and also facilitating increased penile size. Moreover, replacement with follicle-stimulating hormone increases the testicular Sertoli cell population, measurable as an increase in testicular volume and inhibin B, thus hypothetically increasing the capacity for spermatogenesis in adult life for these patients. However, long-term follow-up data is limited for both outcomes pertaining to fertility and nonreproductive sequelae, including neurodevelopment and psychological well-being. The use of international registries for patients with gonadotropin deficiency is a key element in the collection of high-quality, geographically widespread data to inform best-practice management from birth to adulthood.
PubMed: 38924109
DOI: 10.1111/nyas.15177 -
PloS One 2024The development of a cancer vaccine has become an essential focus in the field of medical biotechnology and immunology. In our study, the NY-SAR-35 cancer/testis antigen...
Bioinformatics design of a peptide vaccine containing sarcoma antigen NY-SAR-35 epitopes against breast cancer and evaluation of its immunological function in BALB/c mouse model.
The development of a cancer vaccine has become an essential focus in the field of medical biotechnology and immunology. In our study, the NY-SAR-35 cancer/testis antigen was targeted to design a novel peptide vaccine using bioinformatics tools, and BALB/c mice were used to evaluate the vaccine's immunological function. This evaluation involved assessing peptide-specific IgG levels in the serum via ELISA and measuring the levels of IFN-γ, IL-4, and granzyme B in the supernatant of cultured splenocytes. The final vaccine construct consisted of two T lymphocyte epitopes linked by the AAY linker. This construct displayed high antigenicity, non-allergenicity, non-toxicity, stability, and ability to induce IFN-γ and IL-4. It showed stable dynamics with both human MHC-I and II molecules, as well as mouse MHC-II molecules, and revealed strong Van der Waals and electrostatic energies. Emulsifying our peptide vaccine in incomplete Freund's adjuvant resulted in a remarkable increase in the levels of IgG. The splenocytes of mice that received the combination of peptide and adjuvant displayed a noteworthy increase in IFN-γ, IL-4, and granzyme B secretion. Additionally, their lymphocytes exhibited higher proliferation rates compared to the control group. Our data demonstrated that our vaccine could stimulate a robust immune response, making it a promising candidate for cancer prevention. However, clinical trials are necessary to assess its efficacy in humans.
Topics: Animals; Cancer Vaccines; Mice, Inbred BALB C; Mice; Female; Antigens, Neoplasm; Computational Biology; Humans; Vaccines, Subunit; Breast Neoplasms; Epitopes, T-Lymphocyte; Interleukin-4; Interferon-gamma; Immunoglobulin G; Granzymes; Disease Models, Animal; Protein Subunit Vaccines
PubMed: 38923980
DOI: 10.1371/journal.pone.0306117 -
Veterinary Sciences Jun 2024This prospective study investigated the ultrasonographic appearance of the canine testis from birth to adulthood. Eight purpose-bred laboratory Beagle-breed dogs were...
This prospective study investigated the ultrasonographic appearance of the canine testis from birth to adulthood. Eight purpose-bred laboratory Beagle-breed dogs were monitored from 4 to 40 weeks of life. The following parameters were evaluated every two weeks: bodyweight and height, scrotal and testicular volume, ultrasonographically measured testicular volume, echogenicity, heterogeneity, blood-flow score, ratio of the grayscale intensity value of the testis to the capsule, ejaculate volume, motility, viability, and number of spermatozoa. A correlation analysis was carried out between the various measurements obtained. Fertility was achieved in the 36th week of life. The echogenicity of the testicular parenchyma increased with age, and subsequently to the 30th week of life remained constant. The heterogeneity of the testicular parenchyma, as was evaluated by the standard deviation of the values of grayscale intensity of the parenchyma, also increased with age and was >19 at the onset of fertility. The ratio of grayscale intensity of testicular parenchyma had values < 200 at maturity. A colour Doppler evaluation first detected blood flow in the testis in the 22nd week. After the 32nd week, distinct signals were visible. In the 36th week, >80% of the testes imaged had visible vessels. A significant correlation was found between all the evaluation methods. The findings of the study may help clinicians detect the onset of fertility in dogs, especially when semen evaluation is not feasible; however, their applicability in all breeds or individuals might possibly vary due to genetic, physiological, and developmental differences. In summary, the study ultrasonographically explores the testicular maturity in dogs, with the aim to improve clinical assessments and health management in these animals.
PubMed: 38922017
DOI: 10.3390/vetsci11060270 -
Veterinary Sciences Jun 2024Platelet-derived growth factor B (PDGFB), as an important cellular growth factor, is widely involved in the regulation of cellular events such as cell growth,...
Platelet-derived growth factor B (PDGFB), as an important cellular growth factor, is widely involved in the regulation of cellular events such as cell growth, proliferation, and differentiation. Although important, the expression characteristics and biological functions in the mammalian reproductive system remain poorly understood. In this study, the PDGFB gene of Tibetan sheep was cloned by RT-PCR, and its molecular characteristics were analyzed. Subsequently, the expression of the PDGFB gene in the testes and epididymides (caput, corpus, and cauda) of Tibetan sheep at different developmental stages (3 months, 1 year, and 3 years) was examined by qRT-PCR and immunofluorescence staining. A bioinformatic analysis of the cloned sequences revealed that the CDS region of the Tibetan sheep PDGFB gene is 726 bp in length and encodes 241 amino acids with high homology to other mammals, particularly goats and antelopes. With the increase in age, PDGFB expression showed an overall trend of first decreasing and then increasing in the testis and epididymis tissues of Tibetan sheep, and the PDGFB mRNA expression at 3 months of age was extremely significantly higher than that at 1 and 3 years of age ( < 0.05). The PDGFB protein is mainly distributed in testicular red blood cells and Leydig cells in Tibetan sheep at all stages of development, as well as red blood cells in the blood vessel, principal cells, and the pseudostratified columnar ciliated epithelial cells of each epididymal duct epithelium. In addition, PDGFB protein expression was also detected in the spermatocytes of the 3-month-old group, spermatids of the 1-year-old group, spermatozoa and interstitial cells of the 3-year-old group, and loose connective tissue in the epididymal duct space in each developmental period. The above results suggest that the PDGFB gene, as an evolutionarily conserved gene, may play multiple roles in the development and functional maintenance of testicular cells (such as red blood cells, Leydig cells, and germ cells) and epididymal cells (such as red blood cells, principal cells, and ciliated epithelial cells) during testicular and epididymal development, which lays a foundation for the further exploration of the mechanisms by which the PDGFB gene influences spermatogenesis in Tibetan sheep.
PubMed: 38922013
DOI: 10.3390/vetsci11060266 -
Veterinary Sciences May 2024Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for... (Review)
Review
Management of breeding stallions is crucial to equine reproduction. The longevity of the breeding career is the ultimate objective, whether the stallion is used for natural cover or for semen collection and artificial insemination. Stud farm veterinarians should be aware of the techniques used to evaluate testicular function and the diagnostic approach to testicular disorders in cases of emergency. This paper presents the clinical methods used to evaluate testicular health, including palpation, ultrasonography, biopsy, and fine-needle aspiration. The discussion of testicular disorders is broken down into four categories: congenital disorders (cryptorchidism, monorchidism, and testicular hypoplasia), differential diagnosis of scrotal enlargement, differential diagnosis of causes of progressive testicular enlargement, and differential diagnosis of testicular asymmetry or reduction in size with an emphasis on testicular degeneration. The sudden increase in testicular size is often accompanied by severe clinical signs and is a major cause for referral of stallion for surgery. Testicular disorders are illustrated with clinical cases seen by the authors.
PubMed: 38921990
DOI: 10.3390/vetsci11060243 -
Insects Jun 2024(Busck) is a pest of rosaceous fruit plants worldwide. Due to a combination of monandry and promiscuity in , the age and mating history of both sexes significantly...
(Busck) is a pest of rosaceous fruit plants worldwide. Due to a combination of monandry and promiscuity in , the age and mating history of both sexes significantly affected the mating and reproductive success. In this study, the interactions of different ages (3, 5, or 7 days) and mating history (unmated or mated) in each sex on the mating selection, reproductive system, and offspring production were investigated in the laboratory. The results showed that these differences mainly occurred in young females or males, associated with unmated or mated state. Especially, the 3-day-old unmated females were preferred by the 7-day-old males but discriminated against by the 3- or 5-day-old unmated males, whereas the 3-day-old mated males were preferred by the 3-day-old mated or 7-day-old females but discriminated against by the 3- or 5-day-old unmated females. The lengths of the ovarian ducts were affected by age in the unmated females, with the greatest length being found at 7 days old. The size of testes varied with age in the unmated males, being the largest at 3 days old. At 3 days old, the testes size of the unmated males was larger than that of the mated males. The pairing of 5-day-old unmated females × 3-day-old mated males maximized the successful matings. The least productive pairing was 7-day-old unmated females × 5-day-old mated males. The pairing of 5-day-old mated males × 3-day-old mated females had the lowest number of matings and the highest number of offspring. The pairing of 3-day-old mated females × 3-day-old mated males had a high rate of mating success and the most offspring. These results revealed the different roles between females and males because of physiological states in terms of the reproductive biology in .
PubMed: 38921171
DOI: 10.3390/insects15060457