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Noro Psikiyatri Arsivi 2024There is a significant, but poorly understood, male preponderance in prevalence of autism spectrum disorder (ASD). The aim of this study was to examine the relationship...
INTRODUCTION
There is a significant, but poorly understood, male preponderance in prevalence of autism spectrum disorder (ASD). The aim of this study was to examine the relationship between male preponderance in ASD and Inhibin B (InhB) and Anti-Müllerian hormone (AMH) levels and the 2D/4D finger ratio associated with fetal androgen exposure.
METHODS
42 patients with ASD and 42 neurotypical controls between the ages of 5 and 10 were included. ASD diagnosis and severity were determined using K-SADS PL (Kiddie-SADS - Present and Life Time) Version 2016 and the Childhood Autism Rating Scale (CARS). Serum InhB and AMH were measured. The 2D/4D finger length ratio was also calculated for hand anthropometric measurements.
RESULTS
Serum InhB levels were higher in children diagnosed with ASD compared to the neurotypical controls (p=0.003). Serum AMH levels were similar in both groups. Positive correlation was determined between AMH and CARS scores (r=0.315, p=0.05). 2D/4D finger ratios in the ASD group were significantly lower than in the control group (p<0.001).
CONCLUSION
The study findings suggest that InhB, AMH, and fetal testosterone may be associated with male preponderance in ASD. More research is now required for a better understanding of this subject.
PubMed: 38868849
DOI: 10.29399/npa.28378 -
International Journal of Reproductive... Mar 2023Bisphenol A (BPA), an endocrine-disrupting agent, is widely used as polycarbonate plastics for producing food containers. BPA exposure at environmentally relevant...
BACKGROUND
Bisphenol A (BPA), an endocrine-disrupting agent, is widely used as polycarbonate plastics for producing food containers. BPA exposure at environmentally relevant concentrations can cause reproductive disorders.
OBJECTIVE
The effect of Naringenin (NG) on BPA-induced Sertoli cell toxicity and its mechanism was examined in the present study.
MATERIALS AND METHODS
In this experimental-laboratory study, the mouse TM4 cells were treated to BPA (0.8 μM) or NG for 24 hr at concentrations of 10, 20, and 50 μg/ml. Cell viability, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, antioxidant level, and mitochondrial membrane potential (MMP) were examined. The expression of mitophagy-related genes, including Parkin and PTEN-induced putative kinase 1 (Pink1), was also evaluated.
RESULTS
BPA significantly lowered the viability of the Sertoli cells (p= 0.004). Pink1 and Parkin levels of the BPA group were significantly increased (p 0.001), while the MMP was considerably decreased (p 0.001). BPA raised MDA and ROS levels (p 0.001) and reduced antioxidant biomarkers (p= 0.003). NG at the 20 and 50 μg/ml concentrations could significantly improve the viability and MMP of TM4 cells (p= 0.034). NG depending on concentration, could decrease Pink1 and Parkin at mRNA and protein levels compared to the BPA group (p = 0.024). NG enhanced antioxidant factors, while ROS and MDA levels were decreased in the BPA-exposed cells.
CONCLUSION
The beneficial impacts of NG on BPA-exposed Sertoli cells are related to the suppression of mitophagy and the reduction of oxidative stress.
PubMed: 38868445
DOI: 10.18502/ijrm.v22i3.16166 -
Lipids in Health and Disease Jun 2024The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to...
BACKGROUND
The management of male infertility continues to encounter an array of challenges and constraints, necessitating an in-depth exploration of novel therapeutic targets to enhance its efficacy. As an eight-carbon medium-chain fatty acid, octanoic acid (OCA) shows promise for improving health, yet its impact on spermatogenesis remains inadequately researched.
METHODS
Mass spectrometry was performed to determine the fatty acid content and screen for a pivotal lipid component in the serum of patients with severe spermatogenesis disorders. The sperm quality was examined, and histopathological analysis and biotin tracer tests were performed to assess spermatogenesis function and the integrity of the blood-testis barrier (BTB) in vivo. Cell-based in vitro experiments were carried out to investigate the effects of OCA administration on Sertoli cell dysfunction. This research aimed to elucidate the mechanism by which OCA may influence the function of Sertoli cells.
RESULTS
A pronounced reduction in OCA content was observed in the serum of patients with severe spermatogenesis disorders, indicating that OCA deficiency is related to spermatogenic disorders. The protective effect of OCA on reproduction was tested in a mouse model of spermatogenic disorder induced by busulfan at a dose 30 mg/kg body weight (BW). The mice in the study were separated into distinct groups and administered varying amounts of OCA, specifically at doses of 32, 64, 128, and 256 mg/kg BW. After evaluating sperm parameters, the most effective dose was determined to be 32 mg/kg BW. In vivo experiments showed that treatment with OCA significantly improved sperm quality, testicular histopathology and BTB integrity, which were damaged by busulfan. Moreover, OCA intervention reduced busulfan-induced oxidative stress and autophagy in mouse testes. In vitro, OCA pretreatment (100 µM) significantly ameliorated Sertoli cell dysfunction by alleviating busulfan (800 µM)-induced oxidative stress and autophagy. Moreover, rapamycin (5 µM)-induced autophagy led to Sertoli cell barrier dysfunction, while OCA administration exerted a protective effect by alleviating autophagy.
CONCLUSIONS
This study demonstrated that OCA administration suppressed oxidative stress and autophagy to alleviate busulfan-induced BTB damage. These findings provide a deeper understanding of the toxicology of busulfan and a promising avenue for the development of novel OCA-based therapies for male infertility.
Topics: Male; Animals; Blood-Testis Barrier; Busulfan; Caprylates; Oxidative Stress; Mice; Sertoli Cells; Humans; Spermatogenesis; Autophagy; Infertility, Male; Testis; Spermatozoa; Adult
PubMed: 38862993
DOI: 10.1186/s12944-024-02157-2 -
Ecotoxicology and Environmental Safety Jul 2024Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The...
Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO + intraperitoneal injection with 30 μg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 μM NaAsO) or arsenic + NGF (10 μM NaAsO + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury.
Topics: Animals; Male; Sertoli Cells; Nerve Growth Factor; Mice; Arsenic; Testis; Blood-Testis Barrier; Spermatogenesis; Apoptosis; Tight Junctions
PubMed: 38861803
DOI: 10.1016/j.ecoenv.2024.116578 -
Chinese Medical Journal Jun 2024Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus,...
Male infertility has become a global concern, accounting for 20-70% of infertility. Dysfunctional spermatogenesis is the most common cause of male infertility; thus, treating abnormal spermatogenesis may improve male infertility and has attracted the attention of the medical community. Mitochondria are essential organelles that maintain cell homeostasis and normal physiological functions in various ways, such as mitochondrial oxidative phosphorylation (OXPHOS). Mitochondrial OXPHOS transmits electrons through the respiratory chain, synthesizes adenosine triphosphate (ATP), and produces reactive oxygen species (ROS). These mechanisms are vital for spermatogenesis, especially to maintain the normal function of testicular Sertoli cells and germ cells. The disruption of mitochondrial OXPHOS caused by external factors can result in inadequate cellular energy supply, oxidative stress, apoptosis, or ferroptosis, all inhibiting spermatogenesis and damaging the male reproductive system, leading to male infertility. This article summarizes the latest pathological mechanism of mitochondrial OXPHOS disorder in testicular Sertoli cells and germ cells, which disrupts spermatogenesis and results in male infertility. In addition, we also briefly outline the current treatment of spermatogenic malfunction caused by mitochondrial OXPHOS disorders. However, relevant treatments have not been fully elucidated. Therefore, targeting mitochondrial OXPHOS disorders in Sertoli cells and germ cells is a research direction worthy of attention. We believe this review will provide new and more accurate ideas for treating male infertility.
PubMed: 38855875
DOI: 10.1097/CM9.0000000000003126 -
Clinical and Experimental Reproductive... Jun 2024Some age-related testicular changes, such as Sertoli cell vacuolization and blood-testis barrier breakdown, reduce total sperm production and male fertility. Therefore,...
OBJECTIVE
Some age-related testicular changes, such as Sertoli cell vacuolization and blood-testis barrier breakdown, reduce total sperm production and male fertility. Therefore, this study investigated the effect of vitamin E on restoring testicular function in aged mice. Sperm cryo-resistance was also assessed.
METHODS
Twenty-eight 48-week-old male Naval Medical Research Institute mice were divided into four groups for a daily gavage of vitamin E: the control group received distilled water, while the three treatment groups were administered 100, 200, and 400 mg/kg, respectively, for 4 weeks. Subsequently, semen analyses, DNA fragmentation index (DFI), and protamine deficiency tests were conducted. Testicular histology, tissue antioxidant enzyme activity, and gene expression levels were also assessed.
RESULTS
The two higher dosages of vitamin E were associated with a higher sperm count, greater progressive motility, and improved sperm morphology (p<0.05). These benefits were also evident after sperm freezing (p<0.05). Although chromatin abnormalities increased following vitrification, the treatment groups showed better outcomes (p<0.05). The tubular diameter, epithelium height, and luminal diameters remained unchanged with age. The tissue antioxidant capacity was greater in the groups receiving the high doses of vitamin E. Additionally, significant increases in inhibitor of DNA binding protein-4 (Id4) and GDNF family receptor alpha-1 (Gfra1) expression were observed in the higher vitamin E dosage groups, and promyelocytic leukemia zinc finger protein (Plzf) expression was notably present in the 400 mg/kg treatment group compared to the control group (p<0.05).
CONCLUSION
Antioxidant supplementation might enhance reproductive outcomes in aging males. The observed effects included improved sperm cryo-resistance, which is advantageous for future applications such as sperm freezing or fertility preservation.
PubMed: 38853131
DOI: 10.5653/cerm.2023.06632 -
Clinical and Experimental Reproductive... Jun 2024Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G...
OBJECTIVE
Osteocalcin (OCN) influences spermatogenesis in conjunction with testosterone and estrogen. OCN facilitates the secretion of testosterone by engaging with G protein-coupled receptor class C group 6 member A (GPRC6A) on Leydig cells and with androgen receptors on Sertoli cells.
METHODS
Adult mice were assigned to the following groups: control; sham I, which received dimethyl sulfoxide for 5 weeks followed by phosphate-buffered saline for 1 month; azoospermia, which was treated with busulfan (40 mg/kg); sham II, which consisted of azoospermic animals that received phosphate-buffered saline for 1 month beginning at the 5-week mark; and the experimental group, which included azoospermic mice treated with OCN (3 ng/g/day) for 1 month.
RESULTS
In the mice receiving OCN treatment, immunohistochemical analysis revealed increased expression of androgen receptors and GPRC6A, indicative of enhanced spermatogenesis. Additionally, the expression levels of the cyclic adenosine monophosphate-responsive element binding protein 1, steroidogenic acute regulatory protein, and cytochrome P450 family 11 genes were elevated. However, testosterone levels exhibited no significant differences across groups. Morphometric analysis suggests that OCN may play a crucial role in spermatogenesis, as evidenced by its positive effects on germinal cells and the germinal epithelium in the azoospermia group (p<0.05).
CONCLUSION
We conclude that OCN may serve as a beneficial therapeutic agent for male infertility.
PubMed: 38853130
DOI: 10.5653/cerm.2023.06674 -
Ecotoxicology and Environmental Safety Jul 2024Phenanthrene (Phe), a typical low-molecular-weight polycyclic aromatic hydrocarbon (PAH) of three benzene rings, is one of the most abundant PAHs detected in daily...
Phenanthrene (Phe), a typical low-molecular-weight polycyclic aromatic hydrocarbon (PAH) of three benzene rings, is one of the most abundant PAHs detected in daily diets. Pregnant women and infants are at great risk of Phe exposure. In the present study, Phe was administered to pregnant mice at a dose of 0, 60, or 600 μg/kg body weight six times, and the F1 male mice showed significant reproductive disorders: the testicular weight and testis somatic index were significantly reduced; the levels of serum testosterone, GnRH and SHBG were increased, while the FSH levels were reduced; histological analysis showed that the amount of Sertoli cells and primary spermatocytes in seminiferous tubules was increased, while the amount of secondary spermatocytes and spermatids were decreased in Phe groups. The protein levels of PCNA and androgen receptor were reduced. Differently expressed genes in the testis screened by RNA sequence were enriched in antioxidant capacity, reproduction et al.. Further biochemical tests confirmed that the antioxidant capacity in the F1 testis was significantly inhibited by treatment with Phe during pregnancy. Those results suggested that gestational Phe exposure disordered hypothalamic-pituitary-gonadal (HPG) hormones on the one hand, and on the other hand reduced testicular antioxidant capacity and further arrested cell cycle in F1 adult male mice, which co-caused the inhibition of spermatogenesis.
Topics: Animals; Male; Spermatogenesis; Female; Mice; Phenanthrenes; Pregnancy; Testis; Testosterone; Administration, Oral; Receptors, Androgen; Gonadotropin-Releasing Hormone; Prenatal Exposure Delayed Effects
PubMed: 38850701
DOI: 10.1016/j.ecoenv.2024.116566 -
PloS One 2024Cystic spermatogenesis in the subadult, maturing and adult Greenland shark (Somniosus microcephalus) displays multiple novel features, characterized early on by an...
Aspects of spermatogenesis in immature and mature specimens of the long-lived Greenland shark: Novelties concerning the germinal compartment's assembly, complement of Sertoli cells and demise.
Cystic spermatogenesis in the subadult, maturing and adult Greenland shark (Somniosus microcephalus) displays multiple novel features, characterized early on by an unorganized internal cellular environment of the spermatocysts (anatomically discrete follicle-like units containing a single germ cell stage and its complement of co-developing Sertoli cells). These typically show polar asymmetries due to asymmetrically distributed germ and Sertoli cells. These arise from several novel cellular rearrangements at the immature pole, including fusion of a cluster of somatic cells with newly formed cysts containing only one to three spermatogonia and that already display an excess of Sertoli cells. The subadult's germinative zone revealed an additional novelty, namely numerous previously formed somatic cell-lined rings into which spermatogonia were incorporated. A striking finding was the conspicuous rarity of the routinely discernible Sertoli mitotic figures in the hallmark cyst stage of diametric elasmobranch spermatogenesis that is known for the peak display of the latter. Scrutiny of sequentially unfolding phenomena in the linearly arranged spermatogonial generations revealed that the cellular developments at the most common type of cyst-duct transition area (comprising slender to spindle-like basophilic cells with pointed ends) were concurrent with the discreet appearance of a second dark Sertoli nucleus, a development that persisted in spermiated cysts. Spermatogenically active mature males displayed vigorous meiotic divisions. However, a scattering of their spermatid cysts also displayed shark-atypical asynchronous passage through spermiogenesis, phenomena which were exacerbated as arrested spermiogenesis in an archival collection of tissues from 13 maturing specimens. Subadult specimens revealed meiotic arrest, and foci of infiltration of leukocytes that originate from a mass of eosinophilic, granule-laden immune cells dorsally under the testis capsule. This tissue was identical to the testis-affixed bone marrow equivalent in other shark species. This tissue is likely developmentally regulated in the Greenland shark as it is absent in adults.
Topics: Animals; Male; Sharks; Sertoli Cells; Spermatogenesis; Spermatogonia; Testis
PubMed: 38848382
DOI: 10.1371/journal.pone.0304475 -
Frontiers in Endocrinology 2024Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli... (Review)
Review
Non-obstructive azoospermia (NOA) is a disease characterized by spermatogenesis failure and comprises phenotypes such as hypospermatogenesis, mature arrest, and Sertoli cell-only syndrome. Studies have shown that FA cross-linked anemia (FA) pathway is closely related to the occurrence of NOA. There are FA gene mutations in male NOA patients, which cause significant damage to male germ cells. The FA pathway is activated in the presence of DNA interstrand cross-links; the key step in activating this pathway is the mono-ubiquitination of the FANCD2-FANCI complex, and the activation of the FA pathway can repair DNA damage such as DNA double-strand breaks. Therefore, we believe that the FA pathway affects germ cells during DNA damage repair, resulting in minimal or even disappearance of mature sperm in males. This review summarizes the regulatory mechanisms of FA-related genes in male azoospermia, with the aim of providing a theoretical reference for clinical research and exploration of related genes.
Topics: Animals; Humans; Male; Azoospermia; DNA Damage; DNA Repair; Fanconi Anemia Complementation Group Proteins; Signal Transduction; Spermatogenesis
PubMed: 38846492
DOI: 10.3389/fendo.2024.1393111