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Novel Nuclear Roles for Testis-Specific ACTL7A and ACTL7B Supported by In Vivo Characterizations and AI Facilitated In Silico Mechanistic Modeling with Implications for Epigenetic Regulation in Spermiogenesis.

A mechanistic role for nuclear function of testis-specific actin related proteins (ARPs) is proposed here through contributions of ARP subun … regulation during germline development. This study confirms the intranuclear presence of ACTL7B in spermatocytes and round spermatids, revealing a potential role in intranuclear processes, and identifies a putative nuclear localization sequence conserved across mammalian ACTL7B, indicating a potentially unique mode of nuclear transport which differs from conve …

Light and electron microscopic study of the toxic effect of prolonged lead exposure on the seminiferous tubules of albino rats and the possible protective effect of ascorbic acid.

BACKGROUND: Lead has been long recognized as an occupational toxicant. Now, lead is considered to be one of the major environmental pollutan … tubules with wide lumen and vacuolations in the spermatogenic epithelium mostly separating primary spermatocytes from spermatogonia and surrounding nuclei of Sertoli cells. Apoptotic bodies were found among the basal part of the spermatogenic epithelium. Ultrastructural examination of the same group revealed degenerating cells with cytoplasmic vacuolations, ap …

Androgen receptor roles in spermatogenesis and fertility: lessons from testicular cell-specific androgen receptor knockout mice.

Androgens are critical steroid hormones that determine the expression of the male phenotype, including the outward development of secondary sex characteristics as well as the initiation and maintenance of spermatogenesis. Their actions are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. AR functions as a ligand-dependent transcription factor, regulating expression of an array of androgen-responsive genes. Androgen and the AR play important roles in male spermatogenesis and fertility. The recent generation and characterization of male total and conditional

Short- and long-term effects of immunization against gonadotropin-releasing hormone, using Improvac, on sexual maturity, reproductive organs and sperm morphology in male pigs.

The objective of this study was to determine the short and long term effects of a gonadotropin-releasing hormone (GnRH) vaccine (Improvac Pfizer Ltd.), on sexual maturity, development of the reproductive organs, and the morphology of caudal epididymal spermatozoa in non-castrated male pigs. The pigs were slaughtered 4, 16 or 22 weeks after the second Improvac vaccination. A total of 80 crossbred non-castrated male pigs were included in this study comprising two experiments, a short-effect (Experiment 1) and a long-effect (Experiment 2). The first experiment included 56 pigs, 24 of them were ma

Circulating inhibin alpha concentrations in infant, prepubertal, and adult male rhesus monkeys (Macaca mulatta) and in juvenile males during premature initiation of puberty with pulsatile gonadotropin-releasing hormone treatment.

Circulating inhibin alpha concentrations were determined in infant, juvenile, and adult male rhesus monkeys with a RIA employing antisera to … ation with GnRH stimulation, maturation of the germinal epithelium did not progress past prophase I spermatocytes, and the number of these latter cells was meager. These findings indicate that the testis of the infant primate, like that of the adult, secretes significant amounts of inhibin, and that the quiescent Sertoli cell of the juvenile males may be readil …

NBS1 is required for SPO11-linked DNA double-strand break repair in male meiosis.

DNA double-strand breaks (DSBs) pose a serious threat to genomic stability. Paradoxically, hundreds of programed DSBs are generated by SPO11 in meiotic prophase, which are exclusively repaired by homologous recombination (HR) to promote obligate crossover between homologous chromosomes. In somatic cells, MRE11-RAD50-NBS1 (MRN) complex-dependent DNA end resection is a prerequisite for HR repair, especially for DSBs that are covalently linked with proteins or chemicals. Interestingly, all meiotic DSBs are linked with SPO11 after being generated. Although MRN complex's function in meiotic DSB rep

Genomic instability in mice lacking histone H2AX.

Higher order chromatin structure presents a barrier to the recognition and repair of DNA damage. Double-strand breaks (DSBs) induce histone H2AX phosphorylation, which is associated with the recruitment of repair factors to damaged DNA. To help clarify the physiological role of H2AX, we targeted H2AX in mice. Although H2AX is not essential for irradiation-induced cell-cycle checkpoints, H2AX-/- mice were radiation sensitive, growth retarded, and immune deficient, and mutant males were infertile. These pleiotropic phenotypes were associated with chromosomal instability, repair defects, and impa

Prediction model of male reproductive function damage caused by CHOP chemotherapy regimen for non-Hodgkin's lymphoma.

OBJECTIVE: The CHOP combined chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone) is commonly used to treat non … howed that CAMP, Caspase3, CSF-1, GDNF, IL-1, IL-6, PRKACB, TGF-β1 and TXNDC5 were all expressed in spermatocytes, and the expression of therapeutic histones was significantly higher than that of the control group. Western blot analysis further detected the protein expression, and QPCR detected the mRNA content. The results showed that the expression of histone …

The effect of endurance training with Maca or ginger on steroidogenesis and antioxidant status of testicular tissue in male rats.

Today's primary approach to enhancing reproductive function involves lifestyle modifications, dietary adjustments, the use of herbal supplem … P-1). Spermatogenesis was assessed by counting the number of spermatogenic cells (spermatogonia and spermatocytes), Leydig and Sertoli cells, and characteristics of the seminiferous tubules. Testicular levels of GPx, MDA, and TAC were evaluated. The gene expression of P450Scc and P450c17 were upregulated in the ginger (P = 0.03) (P = 0.03), endurance training ( …

In vivo effect of recombinant Fsh and Lh administered to meagre (Argyrosomus regius) at the initial stages of sex differentiation.

Recombinant gonadotropins, follicle stimulating (rFsh) and luteinizing hormone (rLh), offer the potential to induce gametogenesis in prepube … he 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 decrea …

[Qilin Pills promote testicular spermatogenesis in azoospermia mice].

OBJECTIVE: To investigate the effect of Qilin Pills (QP) in facilitating the recovery of spermatogenic function in azoospermia (AS) mice and to explore its mechanism of regulating testicular spermatogenesis. METHODS: Fifteen 4-week-old male mice were equally randomized into an AS model control, a low-dose QP and a high-dose QP group. The AS model was established in the mice by intraperitoneal injection of busulfan at 35 mg/kg. After modeling, the animals in the low- and high-dose QP groups were treated with Qilin Pills intragastrically at 2 000 and 8 000 mg/kg/d respectively while those in th

Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2) depletion regulates spermatogenic cell apoptosis and is correlated with hypospermatogenesis.

Phosphoribosyl-pyrophosphate synthetase 2 (PRPS2) is a rate-limiting enzyme and plays an important role in purine and pyrimidine nucleotide synthesis. Recent studies report that PRPS2 is involved in male infertility. However, the role of PRPS2 in hypospermatogenesis is unknown. In this study, the relationship of PRPS2 with hypospermatogenesis and spermatogenic cell apoptosis was investigated. The results showed that PRPS2 depletion increased the number of apoptotic spermatogenic cells in vitro. PRPS2 was downregulated in a mouse model of hypospermatogenesis. When PRPS2 expression was knocked d

Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies.

Despite progress in human reproductive biology, the cause of male infertility often remains unknown, due to the lack of appropriate and convenient in vitro models of meiosis. Induced pluripotent stem cells (iPSCs) derived from the cells of infertile patients could provide a gold standard model for generating primordial germ cells and studying their development and the process of spermatogenesis. We report the characterization of a complex chromosomal rearrangement (CCR) in an azoospermic patient, and the successful generation of specific-iPSCs from PBMC-derived erythroblasts. The CCR was chara

RFX2 Is a Major Transcriptional Regulator of Spermiogenesis.

Spermatogenesis consists broadly of three phases: proliferation of diploid germ cells, meiosis, and finally extensive differentiation of the haploid cells into effective delivery vehicles for the paternal genome. Despite detailed characterization of many haploid developmental steps leading to sperm, only fragmentary information exists on the control of gene expression underlying these processes. Here we report that the RFX2 transcription factor is a master regulator of genes required for the haploid phase. A targeted mutation of Rfx2 was created in mice. Rfx2-/- mice are perfectly viable but s

Shilajit mitigates chemotherapeutic drug-induced testicular toxicity: Study on testicular germ cell dynamics, steroidogenesis modulation, and Nrf-2/Keap-1 signaling.

BACKGROUND: Medications, including chemotherapeutic drugs, contribute to male infertility as external factors by inducing oxidative stress in testicular cells. Shilajit is a naturally occurring bioactive antioxidant used in Ayurvedic medicine to treat a variety of ailments. OBJECTIVE: This study examines the potential of Shilajit to counteract the negative effects of the chemotherapeutic drug cyclophosphamide (CPA) on testicular germ cell dynamics. MATERIAL AND METHODS: Male Parkes mice received single intraperitoneal CPA injection (200 mg/kg BW) on day one, followed by daily supplementation

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… The data obtained from the analysis were presented as percentages of different germ cell populations (1C: round spermatid, 2C: spermatogonia, 4C: primary spermatocytes, S-Ph: S-phase germ cells) and germ cell ratios. … PCNA, a well-known biomarker, has been linked to spermatocyte and spermatogonia proliferation [ 58 ]. …

Human-specific subcellular compartmentalization of P-element induced wimpy testis-like (PIWIL) granules during germ cell development and spermatogenesis.

STUDY QUESTION: What is the dynamics of expression of P-element induced wimpy testis-like (PIWIL) proteins in the germline during human feta … revealed the presence of a single dense paranuclear body, resembling the chromatoid body of haploid spermatocytes, in meiotic oocytes. Moreover, in contrast to mice, PIWIL4, but not PIWIL2, localized to the intermitochondrial cement. PIWIL3 was not expressed in GC during development. The upregulation of PIWIL transcripts correlated with the transcription of mar …

A new MEIOB mutation is a recurrent cause for azoospermia and testicular meiotic arrest.

STUDY QUESTION: Are there genetic variants that can be used for the clinical evaluation of azoospermic men? SUMMARY ANSWER: A novel homozygous frame-shift mutation in the MEIOB gene was identified in three azoospermic patients from two different families. WHAT IS KNOWN ALREADY: Up to 1% of all men have complete absence of sperm in the semen, a condition known as azoospermia. There are very few tools for determining the etiology of azoospermia and the likelihood of sperm cells in the testis. The MEIOB gene codes for a single-strand DNA binding protein required for DNA double-strand breaks rep

Molecular mechanisms of libido influencing semen quality in geese through the hypothalamic-pituitary-testicular-external genitalia axis.

Libido plays a crucial role in influencing semen quality, yet the underlying regulatory mechanisms remain unclear. As a central axis in male goose reproduction, the hypothalamic-pituitary-testicular-external genitalia (HPTE) axis may contribute to the regulation of this process. In this study, we established a rating scale for goose libido based on average number of massages to erection (ANM) and the erection type, and evaluated semen quality across the entire flock. Correlation analyses showed that ANM was negatively correlated with sperm concentration (SC), acrosome integrity (AI), and semen

Biallelic HFM1 variants cause non-obstructive azoospermia with meiotic arrest in humans by impairing crossover formation to varying degrees.

STUDY QUESTION: Do variants in helicase for meiosis 1 (HFM1) account for male infertility in humans? SUMMARY ANSWER: Biallelic variants in … fresh testicular samples, the defects of synapsis and crossover formation could not be detected in spermatocytes of patients. Owing to the unavailability of antibodies, we could not quantify the impact of these variants on HFM1 protein levels. WIDER IMPLICATIONS OF THE FINDINGS: Our findings provide direct clinical and in vivo functional evidence that HFM1 va …

Experimental data-sets on sex reversal and histopathological assessment of potential endocrine disrupting effects of graphene oxide on Japanese medaka (Oryzias latipes) larvae at the onset of maturity.

The datasets of this article present the experimental parameters resulting from the assessment of sex reversal (SR) as a biomarker of endocr … rent regions were further analysed by imagej software and used for counting spermatogonia (SPG) and spermatocytes (SPT) in testis as well as perinucleolar (PNO) and cortical alveolar (CAO) oocytes in ovary. Data were expressed as number of SPG or SPT/mm2 testis and % CAO or PNO in an ovary. Preserved tail in TRI reagent was used for genomic DNA extraction and t …