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The epithelial to mesenchymal transition (EMT) in endometrial epithelial and trophectoderm cells is essential for the progression of embryo implantation and its impairment could cause implantation failure. Therefore, EMT should be tightly regulated in both embryonic and endometrial cells during implantation. Studies reported the involvement of numerous factors in EMT regulation, including hormones, growth factors, transcription factors, microRNAs, aquaporins (AQPs), and ion channels. These factors act through different signaling pathways to affect the expression of epithelial and mesenchymal markers as well as the cellular cytoskeleton. Although the mechanisms involved in cancer cell EMT have been well studied, little is known about EMT during embryo implantation. Therefore, we comprehensively reviewed different factors that regulate the EMT, a key event required for the conceptus implantation to the endometrium. Summary sentence: Abnormal epithelial-mesenchymal transition (EMT) process within endometrial epithelial cells (EECs) or trophoblast cells can cause implantation failure. This process is regulated by various factors. Thus, the objective of this review was to summarize the effective factors on the EMT process during implantation.

Electricity- and hydrogen-based sector coupling contributes to realizing the transition towards greenhouse gas neutrality in the European energy system. Energy system and integrated assessment models show that, to follow pathways compatible with the European policy target of net-zero greenhouse gas emissions by 2050, large amounts of renewable electricity and H 2 need to be generated, mostly by scaling-up wind and solar energy production capacity. With a set of such models, under jointly adopted deep decarbonisation scenario assumptions, we here show that the ensuing direct penetration of electricity and H 2 in final energy consumption may rise to average shares of around 60% and 6%, respectively, by 2050. We demonstrate that electrification proves the most cost-efficient decarbonisation route in all economic sectors, while the direct use of H 2 in final energy consumption provides a relatively small, though essential, contribution to deep decarbonisation. We conclude that the variance observed across results from different models reflects the uncertainties that abound in the shape of deep decarbonisation pathways, in particular with regard to the role of H 2 . Multiple energy system models are used under jointly adopted deep decarbonisation scenarios to conclude that the direct penetration of electricity and hydrogen in final energy consumption may rise to shares of, respectively, 60% and 6%, in Europe by 2050.

Recently, the interest of the scientific community is focused on the application of tissue engineering approach for the fertility restoration. In this paper innovative patterned electrospun fibrous scaffolds were fabricated and used as 3D system for porcine follicles culture. The obtained scaffolds demonstrated to be a suitable support which did not alter or interfere with the typical spherical follicles morphology. The fibrillar structure of the scaffolds mimics the morphology of the healthy native tissue. The use of porcine follicles implied many advantages respect to the use of mouse model. Relevant results showed that more than the scaffold pattern and struts dimension, the selection of proper biomaterials improve the follicles adhesion and development.

The nonspecific nature of cancer drug delivery often results in substantial toxic side effects during treatments for breast cancer. To mitigate these negative outcomes, our approach involves loading methotrexate (MTX) within carbon quantum dots (CQDs) synthesized from folic acid, which are then enveloped in exosomal membranes obtained from breast cancer cells (Ex@MTX-CQDs). Analysis utilizing nanoparticle tracking techniques has demonstrated that these Ex@MTX-CQDs maintain the physical and biochemical properties of their exosomal precursors. The release profile of MTX indicated a restricted release percentage (less than 10%) under normal physiological conditions, which is contrasted by a more consistent release rate (approximately 65%) when emulating the conditions found within tumor tissues. The toxicological assessments have confirmed that the presence of exosomes combined with leftover folic acid significantly improves the delivery efficacy of MTX directly to the cancerous cells through the binding to folate and heparan sulfate proteoglycan receptors. This process results in increased disruption of the mitochondrial membrane potential and subsequently triggers apoptosis, ultimately leading to the destruction of cancerous cells. Our research could potentially contribute to the further innovation and application of nanocarriers derived from biological sources for the targeted treatment of breast cancer.

Endometrial-related disorders including Asherman’s syndrome, thin endometrium, pelvic organ prolapse, and cesarean scar pregnancies can be accompanied by different symptoms such as amenorrhea, infertility, abnormal placental implantation and recurrent miscarriage. Different methods have been introduced to overcome these problems such as surgery and hormonal therapy but none of them has shown promising outcomes. On the other hand, the development of novel regenerative therapeutic strategies has opened new avenues for the treatment of endometrial-related deficiencies. In this regard, different types of scaffolds, acellular matrices and also cell therapy with adult or stem cells have been investigated for the treatment of endometrial-related deficiencies. In this paper, we review the current status of cell-based endometrium regeneration using scaffold dependent and scaffold-free methods and future perspectives in this field. Moreover, we discuss the endometrial diseases that can be candidates for cell-based treatments. Also, the cells with the potential for endometrial regeneration are explained.

Background Platelet-rich plasma (PRP) and its subtype, plasma rich in growth factors (PRGF), are autologous blood-derived products that have garnered increasing attention as personalized therapeutic tools in the field of male fertility. This systematic review aims to evaluate the current in vitro and in vivo evidence regarding the potential applications of platelet-derived products in various domains of male reproductive health, including in vitro spermatogenesis, sperm preservation, treatment of male infertility, mitigation of testicular toxicity, and management of testicular torsion/detorsion (T/D) injury. Strategy This review was conducted in accordance with PRISMA guidelines and was prospectively registered in PROSPERO. A comprehensive and language-unrestricted search was performed across major databases, including the Cochrane Library, MEDLINE/PubMed, Scopus, ScienceDirect, and Web of Science. Studies published up to October 2024 were included, with an update in January 2025. Three reviewers independently screened and selected studies, with discrepancies resolved through discussion or consultation with a fourth reviewer. Results A total of 43 studies met the inclusion criteria. Available evidence suggests that PRP and PRGF supplementation in culture media may enhance in vitro sperm generation by improving cell viability and proliferation. Their incorporation into sperm incubation and cryopreservation protocols has also been associated with improved motility, viability, and structural integrity. In vivo studies indicate that intratesticular PRP injections may offer therapeutic benefits for male infertility, potentially supporting improvements in sperm parameters, hormonal balance, and testicular tissue restoration. Additionally, PRP has been reported to reduce testicular toxicity and ischemia–reperfusion injury, possibly through antioxidative and tissue-reparative mechanisms. Conclusion While preliminary findings highlight the promise of PRP and PRGF as emerging, plasma-based approaches in male reproductive medicine, further research is essential to standardize protocols, evaluate long-term efficacy and safety, and elucidate underlying molecular mechanisms before these therapies can be safely and effectively translated into routine clinical practice. Graphical abstract

Selecting the most competent sperm is crucial for improving the success of intracytoplasmic sperm injection (ICSI). Chemotaxis-based sperm selection may facilitate the selection of spermatozoa with superior motility and fertilization capability. This study aimed to evaluate sperm selection based on chemotaxis induced by microvesicles (MVs) derived from follicular fluid (FF) and cumulus cells (CCs) using a simple microfluidic device. In this experimental study, FF and CCs were collected during ovum pick-up from 10 women undergoing ICSI. MVs from both FF and CCs were isolated using the Exocib kit and characterized for particle size, polydispersity index, zeta potential, morphology, and protein content. To establish a chemoattractant gradient, MVs from FF and CCs, as well as progesterone, were incorporated into agar plates. Nine experimental groups were studied: FF- derived MVs (FF-MV, 5, 25, and 50 μg/ml), CC-derived MV (CC-MV, 5, 25, and 50 μg/ml), FF (50 μg/ml), progesterone (0.03 μM), and a control (agar without chemoattractant). Sperm selection was performed in a microfluidic system using semen samples from 20 normozoospermic men. Sperm concentration, motility, progressive motility, viability, and DNA integrity were analyzed following chemotaxis-based selection. The isolated FF-and CC-derived MVs exhibited spherical morphology, a negative zeta potential, and were polydispersed. The progesterone-containing plates showed sustained release. No significant differences were observed between the CC-MV and control groups in sperm parameters (P=0.630). Plates supplemented with 50 μg/mL of FF-MV markedly improved sperm concentration (P=0.002), progressive motility (P=0.010), and DNA integrity (P=0.001) compared to the control group. FF-MVs, particularly at 50 μg/ml, possess chemoattractant properties and could selectively enrich sperm populations with improved functional parameters. These findings highlight the potential of FF-MVs as a novel tool for high-quality sperm selection in the ICSI procedure.

Exosomes, as lipid nanostructure, are secreted by approximately all cell types within the body and actively involved in either short or long distances cell–cell communication in an autocrine and paracrine manner. Recently, exosomes are widely used as a nanocarrier for delivery of various nucleotide- or protein passed molecules including miRNA, and drugs into various cells, as a therapeutic strategy in a broad range of diseases including osteoarthritis. Osteoarthritis is one of the most common debilitating chronic musculoskeletal disorders with a multifaceted condition and an increasing impact on the quality of life. Therefore, this review aims to focus on the current knowledge of the exosomal miRNAs in the osteoarthritis to address their potential therapeutic application.

Non-obstructive azoospermia (NOA) is one of the leading causes of male factor infertility, which results from impaired spermatogenesis. Currently, the sole feasible therapeutic option for men with NOA to father their biologic children is sperm retrieval by testicular sperm extraction (TESE) approaches followed by an intracytoplasmic sperm injection program. Nevertheless, the rate of sperm retrieval from NOA men following TESE has remained as low as 50%, leading to a significant number of unsuccessful TESE operations. Given that TESE is associated with multiple side effects, the prediction of TESE outcome preoperatively can abolish unnecessary operations and thereby prevent NOA patients from sustaining adverse side effects. As the process of spermatogenesis is under the regulation of hormones, the hormonal profile of serum and/or seminal plasma may contain useful information about spermatogenesis status and can potentially predict the chance of sperm retrieval from NOA patients. A large body of literature is available on the predictive capability of different serum and seminal plasma hormones such as FSH, LH, testosterone, inhibin B, AMH, estradiol, prolactin, and leptin in a stand-alone basis or combinational fashion with respect to the TESE outcome. The present review aimed to evaluate the potential of these hormonal markers as noninvasive predictors of sperm retrieval in men with NOA.

Reproductive tissue engineering (REPROTEN) has been recently defined as the application of the tissue engineering approach targeting reproductive organs and several research works are focusing on this novel strategy. Being still an innovative field, most of the scaffold characterization techniques suitable for other tissue targets give inappropriate results, and there is the need to evaluate and investigate novel approaches. In particular the focus of this paper is the evaluation of the infiltration of ovarian follicles inside patterned electrospun scaffolds. Beyond the standard techniques, for the first time the use of magnetic resonance imaging (MRI) for this purpose is proposed and specific protocols for scaffold preparation are reported. Positive results in terms of evaluation of scaffolds incorporating follicles confirm this technique as highly effective for further applications in this field.