In vitro spermatogenesis in artificial testis: current knowledge and clinical implications for male infertility

Men’s reproductive health exclusively depends on the appropriate maturation of certain germ cells known as sperm. Certain illnesses, such as Klinefelter syndrome, cryptorchidism, and syndrome of androgen insensitivity or absence of testis maturation in men, resulting in the loss of germ cells and the removal of essential genes on the Y chromosome, can cause non-obstructive azoospermia. According to laboratory research, preserving, proliferating, differentiating, and transplanting spermatogonial stem cells or testicular tissue could be future methods for preserving the fertility of children with cancer and men with azoospermia. Therefore, new advances in stem cell research may lead to promising therapies for treating male infertility. The rate of progression and breakthrough in the area of in vitro spermatogenesis is lower than that of SSC transplantation, but newer methods are also being developed. In this regard, tissue and cell culture, supplements, and 3D scaffolds have opened new horizons in the differentiation of stem cells in vitro, which could improve the outcomes of male infertility. Various 3D methods have been developed to produce cellular aggregates and mimic the organization and function of the testis. The production of an artificial reproductive organ that supports SSCs differentiation will certainly be a main step in male infertility treatment

The protective effects of astaxanthin on pre-antral follicle degeneration in ovine vitrified/warmed ovarian tissue

This study assesses the protective effects of astaxanthin (AST) against vitrification/warming-induced cryoinjuries of ovarian tissue slices in sheep. Cortical slices of slaughterhouse acquired-ovine ovaries were randomly distributed in different groups: fresh, toxicity, and five vitrification groups including vitrification in presence of 0 (control group), 1, 10 and 100 μM astaxanthin or 100 μM vitamin E. After vitrification/warming and 24 h culturing, the samples were subjected to histological studies, antioxidant evaluation by TAC and TBAR assays, and assessment of relative expression of BMP4, BMP15, GDF9 and KITLG genes related to folliculogenesis and follicular growth regulation. According to the results, vitrification reduced the percentage of morphologically intact follicles compared to the fresh and toxicity groups (p < 0.05). In vitrification groups, vitamin E and all three concentrations of AST increased the percentage of intact pre-antral follicles and antioxidant activity relative to the vitrified control (p < 0.05). This enhancement significantly occurred in 10 μM AST group more than vitamin E (p < 0.05). Also, 10 μM concentration of AST enhanced the expression of all the examined genes compared to the control (p < 0.05), while the expression of BMP4, BMP15 and KITLG was higher in the AST than vitamin E (p < 0.05). The latter could increase only the expression of GDF9 compared to the control group (p = 0.011). In conclusion, AST is a highly effective antioxidant for maintaining the survival of pre-antral follicles, retaining cell density, increasing total antioxidant capacity, and increasing the expression of some genes related to follicular development after short-term culture of vitrified/warmed ovarian tissue slices

Generation of Haploid Spermatids on Silk Fibroin‐Alginate‐Laminin‐Based Porous 3D Scaffolds

In vitro production of sperm is a desirable idea for fertility preservation in azoospermic men and prepubertal boys suffering from cancer. In this study, a biocompatible porous scaffold based on a triad mixture of silk fibroin (SF), alginate (Alg), and laminin (LM) is developed to facilitate the differentiation of mouse spermatogonia stem cells (SSCs). Following SF extraction, the content is analyzed by SDS-PAGE and stable porous 3D scaffolds are successfully prepared by merely Alg, SF, and a combination of Alg-SF, or Alg-SF-LM through freeze-drying. Then, the biomimetic scaffolds are characterized regarding the structural and biological properties, water absorption capacity, biocompatibility, biodegradability, and mechanical behavior. Neonatal mice testicular cells are seeded on three-dimensional scaffolds and their differentiation efficiency is evaluated using real-time PCR, flow cytometry, immunohistochemistry. Blend matrices showed uniform porous microstructures with interconnected networks, which maintained long-term stability and mechanical properties better than homogenous structures. Molecular analysis of the cells after 21 days of culture showed that the expression of differentiation-related proteins in cells that are developed in composite scaffolds is significantly higher than in other groups. The application of a composite system can lead to the differentiation of SSCs, paving the way for a novel infertility treatment landscape in the future

In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin / alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing

Healing diabetic ulcers with chronic inflammation is a major challenge for researchers and professionals, necessitating new strategies. To rapidly treat diabetic wounds in rat models, we have fabricated a composite scaffold composed of alginate (Alg) and silk fibroin (SF) as a wound dressing that is laden with molecules of lithium chloride (LC). The physicochemical, bioactivity, and biocompatibility properties of Alg-SF-LC scaffolds were investigated in contrast to those of Alg, SF, and Alg-SF ones. Afterward, full-thickness wounds were ulcerated in diabetic rats in order to evaluate the capacity of LC-laden scaffolds to regenerate skin. The characterization findings demonstrated that the composite scaffolds possessed favorable antibacterial properties, cell compatibility, high swelling, controlled degradability, and good uniformity in the interconnected pore microstructure. Additionally, in terms of wound contraction, re-epithelialization, and angiogenesis improvement, LC-laden scaffolds revealed better performance in diabetic wound healing than the other groups. This research indicates that utilizing lithium chloride molecules loaded in biological materials supports the best diabetic ulcer regeneration in vivo, and produces a skin replacement with a cellular structure comparable to native skin

Retraction notice to “In-vitro and in-vivo evaluation of angiogenic potential of a novel lithium chloride loaded silk fibroin/alginate 3D porous scaffold with antibacterial activity, for promoting diabetic wound healing” [Int. J. Biol. Macromol. 277(2024) 134362]

This article has been retracted: please see Elsevier policy on article withdrawal (https://www.elsevier.com/about/policies-and-standards/article-withdrawal). The article has been retracted at the request of the Editor-in-Chief. The journal was notified of possible image duplication. An investigation by the editorial office confirmed that the publication contained duplicated images in Figs. 3 and 6, as well as duplications with figures from other publications (https://doi.org/10.1002/mabi.202200574 and https://doi.org/10.1021/acsabm.3c00814). While the corresponding author initially collaborated with the investigation, they were unable to provide satisfactory explanations regarding the image duplications, leading the editors to lose trust in the integrity of the presented data. Additionally, concerns about authorship have been raised, as two co-authors (Morteza Koruji and Ali Mohammad Sharifi) have stated that they never consented to being listed as authors on the submission and were not consulted by the corresponding author. The corresponding author has not responded to the allegations concerning authorship

Drosophila muller f elements maintain a distinct set of genomic properties over 40 million years of evolution.

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25-50%) than euchromatic reference regions (3-11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11-27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4-3.6 vs. 8.4-8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu