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Regulation of the DNA damage response on male meiotic sex chromosomes.

During meiotic prophase in males, the sex chromosomes partially synapse to form the XY body, a unique structure that recruits proteins involved in the DNA damage response, which is believed to be important for silencing of the sex chromosomes. It remains elusive how the DNA damage response in the XY body is regulated. Here we show that H2AX-MDC1-RNF8 signaling, which is well characterized in somatic cells, is dispensable for the recruitment of proteins to the unsynapsed axes in the XY body. On the other hand, the DNA damage response that spreads over the sex chromosomes is largely similar to t

Centripetal structural reorganization of the testis in experimental rheumatoid arthritis and its age-dependent restitution by meloxicam: A morphometric and immunohistochemical study in rats.

BACKGROUND: Rheumatoid arthritis (RA) is a systemic autoimmune disease increasingly implicated in male reproductive impairment, yet the stru … lar outer diameter fell while the lumen widened, mathematically indicating epithelial thinning, and spermatocytes were the most affected population. Leydig-cell density fell by 10.8% and 32.6%. Vimentin (14.7→29.5% and 17.7→45.3%) and the Ki-67 index (18.3→33.8% and 15.1→30.7%) rose significantly (p < 0.05-0.001). Two-way ANOVA showed a significant treatment ef …

Calmin, a protein with calponin homology and transmembrane domains expressed in maturing spermatogenic cells.

A cDNA named calmin of approximately 3.2 kb was isolated by RNA differential display applied to developing mouse skin. Calmin cDNA encodes 1021 amino acids with two calponin homology (CH) domains in tandem on the N-terminal side and a transmembrane domain on the C-terminal side. The region covering the CH domains showed a high level of homology with beta-spectrin, alpha-actinin, and dystrophin. Among the proteins with the tandem CH domains, calmin is unique in having a transmembrane domain. Three alternative splicing sites were identified at the 3'-side of calmin, giving rise to polymorphic pr

Glucagon receptor blockade protects spermatogenesis by enhancing PFKFB3-mediated lactate production in Sertoli cells.

BACKGROUND: Male fertility has declined globally. Diabetes and aging are major contributors to the reduced sperm production and testicular dysfunction. Elevated glucagon signaling leads to diabetic complications, yet its impact on male reproductive function remains unclear. METHODS: Streptozotocin-induced type 1 diabetic mice, naturally aged mice, and healthy young male mice were treated with a glucagon receptor (GCGR) monoclonal antibody or control. Sperm quality and testicular outcomes, including histology, oxidative stress, and apoptosis, were assessed. We then generated global Gcgr knocko

The feasibility of fertility preservation in adolescents with Klinefelter syndrome.

STUDY QUESTION: Is fertility preservation feasible after the onset of puberty in adolescents with Klinefelter syndrome (KS)? SUMMARY ANSWER … a bilateral testicular biopsy. Spermatozoa were retrieved in one patient, elongated spermatids and spermatocytes I in a second patient. LIMITATIONS, REASONS FOR CAUTION: The number of patients enrolled in our study was low because the diagnosis of KS is only rarely made before or at the onset of puberty. Most XXY males are diagnosed in adulthood within the co …

Hesperidin Mitigates Cyclophosphamide-Induced Testicular Dysfunction via Altering the Hypothalamic Pituitary Gonadal Axis and Testicular Steroidogenesis, Inflammation, and Apoptosis in Male Rats.

Cyclophosphamide (CP) is a cytotoxic, cell cycle, non-specific, and antiproliferative drug. This study aimed to address the toxic effects of CP on male fertility and the possible ameliorative role of hesperidin (HSP). Thirty-two adult albino rats were randomly divided into four groups, namely, the negative control, HSP, CP-treated, and CP+HSP-treated groups. The CP-treated rats showed a significant reduction in the levels of serum LH, FSH, testosterone, prolactin, testicular glutathione peroxidase (GPx), and total antioxidant capacity (TAC) with an elevation in levels of malondialdehyde (MDA),

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… A complete series of spermatogenic cells were seen (spermatogonia, primary spermatocytes, secondary spermatocytes and spermatids). The seminiferous tubules were covered by a single layer of myoid cells with flattened nuclei. … Increased testicular apoptosis, as indicated by increased P53 expression, results in spermatogenic arrest and a reduction in spermatogonia, spermatocytes, and spermatid numbers [ 61 ]. …

RNA profiling of human testicular cells identifies syntenic lncRNAs associated with spermatogenesis.

STUDY QUESTION: Is the noncoding transcriptional landscape during spermatogenesis conserved between human and rodents? SUMMARY ANSWER: We i … n average) and only patients with full spermatogenesis were used to prepare enriched populations of spermatocytes, spermatids, Leydig cells, peritubular cells and Sertoli cells. To minimize potential biases linked to inter-patient variations, RNAs from two or three donors were pooled prior to RNA-sequencing (paired-end, strand-specific). Resulting reads were ma …

Effect of thyroid hormone on the development and gene expression of hormone receptors in rat testes in vivo.

Thyroid hormone is known to play a pivotal role in the regulation of prepuberal rat testes development and function with specific influence … n and delayed germ cell differentiation and in hyperthyroid rats an increased number of early stage spermatocytes was found. Testicular mRNA levels of follicle-stimulating hormone receptor (FSH-R), luteinizing hormone receptor (LH-R) and androgen binding protein (ABP) were studied by Northern blot hybridization. At 21 days of age data showed that FSH-R mRNA lev …

Systematic characterization of human testis-specific actin capping protein β3 as a possible biomarker for male infertility.

STUDY QUESTION: Is actin capping protein (CP) β3 involved in human spermatogenesis and male infertility? SUMMARY ANSWER: Human CPβ3 (hCPβ3) … rmatogonia, hCPβ3 showed a slight signal in cytoplasm. hCPβ3 expression was conspicuous mainly from spermatocytes, and hCPβ3 localization dynamically migrated from cytoplasm to the acrosomal cap and acrosome. In mature spermatozoa, hCPβ3 accumulated in the postacrosomal region and less so at the midpiece of the tail. Double-staining analysis revealed that hCPα3 …

Novel variants in YTHDC2 cause non-obstructive azoospermia by disrupting the mitotic-to-meiotic transition in humans and mice.

STUDY QUESTION: Do variants in YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) cause male infertility in humans, and what is the underlying pathogenic mechanism? SUMMARY ANSWER: Biallelic pathogenic missense variants in YTHDC2 disrupt the mitotic-to-meiotic transition, causing meiotic arrest and non-obstructive azoospermia (NOA) or severe oligozoospermia in humans. WHAT IS KNOWN ALREADY: YTHDC2 is a male germ cell-specifically expressed RNA helicase essential for meiotic progression. In mice, loss of Ythdc2 leads to meiotic arrest at the early prophase. However, clinical evidence link

Hidrox® Counteracts Cyclophosphamide-Induced Male Infertility through NRF2 Pathways in a Mouse Model.

BACKGROUND: Every year, men use cyclophosphamide to treat various cancers and autoimmune diseases. On the one hand, this chemotherapy often has the beneficial effect of regressing the tumor, but on the other hand, it leads to infertility due to excessive oxidative stress and apoptosis in the testes caused by its metabolite, acrolein. METHODS: The objective of this study was to evaluate the beneficial power of a new compound called Hidrox®, containing 40-50% hydroxytyrosol, in counteracting the damage related to fertility induced by cyclophosphamide. The study was conducted using a single intr

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… In fact, CYP causes a reduction in the size and number of seminiferous tubules, spermatogonia degeneration and vacuolation, reduced spermatocytes and germ cells, irregular seminiferous tubules, reduced seminiferous epithelial layers, significant maturation arrest, and perivascular fibrosis [ 81 , 103 … It has been demonstrated that spermatocytes and spermatids can produce low levels of ROS, which are required for many physiological processes such as capacitation, hyperactivation, and sperm–oocyte fusion [ 105 ]. …

Gene regulation by non-Coding RNAs in infertility: a mechanistic review.

Infertility is a significant global health issue affecting millions of couples, with noncoding RNAs (ncRNAs) emerging as pivotal regulators in reproductive biology. This review explores the roles of various ncRNAs, including microRNAs (miRNAs), small interfering RNAs (siRNAs), long noncoding RNAs (lncRNAs), PIWI-interacting RNAs (piRNAs), and circular RNAs (circRNAs) in male and female infertility. These ncRNAs modulate critical processes such as spermatogenesis, oogenesis, follicular development, and embryo implantation through mechanisms like post-transcriptional regulation, chromatin remode

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… Although its function in regulating germ cells and SSCs has been previously identified, miR-34c also has a unique function in regulating apoptosis in spermatocytes and round spermatids [ 71 ]. … The transcriptional control of genes unique to this stage of germ cell development has been linked to the important roles of lncRNA-Tcam1 and lncRNA-HSVIII in pachytene spermatocytes. Furthermore, certain lncRNAs have specialized functions. …

[Improving effect of selenium on spermatogenesis in mice with cyclophosphamide-induced spermatogenic impairment and its underlying mechanism].

OBJECTIVE: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying … erroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related …

Long Non-Coding RNAs: Role in Testicular Cancers.

In the last few years lncRNAs have gained increasing attention among the scientific community, thanks to the discovery of their implication in many physio-pathological processes. In particular, their contribution to tumor initiation, progression, and response to treatment has attracted the interest of experts in the oncologic field for their potential clinical application. Testicular cancer is one of the tumors in which lncRNAs role is emerging. Said malignancies already have very effective treatments, which although lead to the development of quite serious treatment-related conditions, such a

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… NLC1-C expression in spermatogonia and early spermatocytes is reflective of its role in the early stages of spermatogenesis ( 101 ). … The formation of mature sperms is a complicated and highly coordinated process which requires not only an initial proliferation of spermatogonia, but also a loss of germ cells during spermatocytes meiosis and spermatids differentiation ( 137 ). …

Açai Berry Attenuates Cyclophosphamide-Induced Damage in Genitourinary Axis-Modulating Nrf-2/HO-1 Pathways.

Cyclophosphamide (CYP) is used to treat different malignancies and autoimmune disorders in men. This chemotherapy frequently reduces tumors, which is beneficial, but also causes infertility because of severe oxidative stress, inflammation, and apoptosis in the bladder and testes brought on by its metabolite, acrolein. The goal of this study was to assess the efficacy of a novel food, açai berry, in preventing CYP-induced damage in the bladder and testes.MethodsCYP was administered intraperitoneally once during the experiment at a dose of 200 mg/kg body weight diluted in 10 mL/kg b.w. of water.

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… CYP leads to perivascular fibrosis, spermatogonia degeneration and vacuolation, diminished spermatocytes and germ cells, irregular seminiferous tubules, diminished seminiferous epithelial layers, severe maturation arrest, and decreased size and number of seminiferous tubules [ 97 , 122 , 123 ]. … Low levels of ROS, which are necessary for numerous physiological processes including capacitation, hyperactivation, and sperm-oocyte fusion, have been shown to be produced by spermatocytes and spermatids. …

Identification of two hidden clinical subgroups among men with idiopathic cryptozoospermia.

STUDY QUESTION: Are there subgroups among patients with cryptozoospermia pointing to distinct etiologies? SUMMARY ANSWER: We reveal two dis … (Cluster 1, all Control patients and two cryptozoospermic patients), the percentage of tubules with spermatocytes (Cluster 2, cryptozoospermic patients), and tubules showing a Sertoli cells only phenotype (Cluster 3, cryptozoospermic patients). Importantly, the percentage of tubules containing elongated spermatids was comparable between Clusters 2 and 3. Additi …

Double jeopardy: how BRCA2, TP53, and DNMT3A redefine the link between infertility and cancer risk.

BackgroundGermline mutations in genes governing DNA repair, cell cycle regulation, and epigenetic modification are now recognized as common etiological factors for both cancer predisposition and reproductive dysfunction. This reveals a profound intersection between reproductive biology and oncogenesis.MethodA systematic narrative review was conducted. The literature search spanned PubMed/MEDLINE, Scopus, and Web of Science using keywords and MeSH terms related to infertility phenotypes, cancer predisposition syndromes, and shared molecular mechanisms (e.g., DNA repair, epigenetics).OutcomesThe

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… increased MLH1/3 foci; unchanged number of chiasmata | Biallelic loss-of-function | Holloway et al. (2011) ; Crossan et al. (2011) ; Bakker et al. (2013) ; Spinella et al. (2015) 27 | FANCS ( Brca1 ) | Breast and ovarian cancer | Reduced testis weight; no spermatozoa; sterile males; fertile females; spermatocytes … In its absence, oocytes and spermatocytes accumulate unrepaired DSBs, leading to premature ovarian insufficiency ( Oktay et al., 2010 ) and BRCA1/2 are required for the completion of embryogenesis ( Tulay et al., 2017 ). …

Assessment of pigmented skin lesions in terms of blood perfusion estimates.

The rising prevalence of vision-threatening eye diseases poses a major global health and economic burden, yet timely diagnosis remains limited by workforce shortages, diagnostic delays, and restricted access to specialized care. Artificial intelligence (AI) offers potential solutions. In particular, recent progress in foundation models and large language models-especially multimodal large language models (MLLMs)-has shown promise in medical image interpretation and automated clinical documentation. However, advancing MLLMs for ophthalmology is hindered by the lack of unified, comprehensive ben

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… Piwi-interacting RNAs in male infertility Unlike miRNAs which are expressed in a variety of tissues and cells, piwi-interacting RNAs (piRNAs) are expressed mainly in germ cells especially pachytene spermatocytes and spermatids in human testes [ 65 ]. piRNAs are longer (about 29 nucleotide-long) than …

The potential value of cancer-testis antigens in ovarian cancer: Prognostic markers and targets for immunotherapy.

BackgroundTumor immunotherapy has become an important adjuvant therapy after surgery, radiotherapy, and chemotherapy. In recent years, the role of tumor-associated antigen (TAA) in tumor immunotherapy has become increasingly prominent. Cancer-testis antigen (CTA) is a kind of TAA that is highly restricted in a variety of tumors and can induce an immune response.AimsThis review article aimed to evaluate the role of CTA on the progression of ovarian cancer, its diagnostic efficacy, and the potential for immunotherapy.MethodsWe analyzed publications and outlined a comprehensive of overview the re

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… The non‐X CT gene is usually expressed in the spermatocyte stage (late stage) of spermatogenesis and is involved in male germ cell differentiation. … HSP70‐2 is required for CDC2 kinase activity in meiosis I of mouse spermatocytes . Development . 1997 ; 124 ( 15 ): 3007 ‐ 3014 . 9247342 10.1242/dev.124.15.3007 50 Gupta N , Jagadish N , Surolia A , Suri A . …

Germ cell tumors of the gonads: a selective review emphasizing problems in differential diagnosis, newly appreciated, and controversial issues.

Gonadal germ cell tumors continue to be the cause of diverse, diagnostically challenging issues for the pathologist, and their correct resolution often has major important therapeutic and prognostic implications. They are academically interesting because of the biological diversity exhibited in the two gonads and variation in frequency of certain neoplasms. The most dramatic examples of the latter are the frequency of dermoid cyst in the ovary compared to the testis and the reverse pertaining to embryonal carcinoma. Within the teratoma group, there is strong evidence that ovarian and prepubert