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Introduction: Malignant bone and soft tissue tumors, commonly called sarcomas, predominantly originate in bone and soft tissues and typically affect individuals at a younger age. Following the resection of the primary tumor, treatment often necessitates radiation therapy and gonadotoxic chemotherapy, the specifics of which depend on the disease's stage Conversely, there is a notable concern regarding the potential loss of fertility due to these treatments. Consequently, it is recommended that men consider sperm cryopreservation before initiating treatment. This study aims to assess spermatogenesis in male patients diagnosed with malignant bone and soft tissue tumors before and after chemotherapy. Methods: This study involved 34 male patients diagnosed with malignant bone and soft tissue tumors and subsequently underwent sperm cryopreservation before initiating treatment. Medical records included details about the primary disease, age, marital status at presentation, semen analysis results, treatment regimen and number of courses, post-treatment semen analysis, renewal status and outcomes. Results: The mean age at the time of sperm cryopreservation was 22.8 years. The median semen volume was 2.5 mL, sperm concentration was 32.6 million/ml, and sperm motility was 38.5%. Following chemotherapy, semen analysis was conducted on 12 patients, with ifosfamide being the predominant drug used in all cases. Among these 12 patients, eight retained viable spermatozoa, and two successfully achieved spontaneous pregnancies resulting in live births. In one of the remaining four cases where no sperm were detected in ejaculate, a live birth was achieved through intracytoplasmic sperm injection using cryopreserved sperm. Discussion: While ifosfamide, the primary chemotherapy drug for patients with malignant bone and soft tissue tumors, was associated with severe impairments in spermatogenesis, recovery of spermatogenesis was observed in many cases. However, there were instances of prolonged azoospermia. Even in such cases, assisted reproduction using cryopreserved sperm remained viable for achieving parenthood. In light of these findings, offering patients the opportunity for fertility preservation is advisable.
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Intracerebroventricular infusion of resolvin E1 (RvE1), a bioactive metabolite derived from eicosapentaenoic acid, exerts antidepressant-like effects in a mouse model of lipopolysaccharide (LPS)-induced depression; these effects are blocked by systemic injection of rapamycin, a mechanistic target of rapamycin complex 1 (mTORC1) inhibitor. Additionally, local infusion of RvE1 into the medial prefrontal cortex (mPFC) or dorsal hippocampal dentate gyrus (DG) produces antidepressant-like effects. To evaluate the potential of RvE1 for clinical use, the present study examined whether treatment with RvE1 via intranasal (i.n.) route, a non-invasive route for effective drug delivery to the brain, produces antidepressant-like effects in LPS-challenged mice using tail suspension and forced swim tests. Intranasal administration of RvE1 significantly attenuated LPS-induced immobility, and these antidepressant-like effects were completely blocked by an AMPA receptor antagonist or L-type voltage-dependent Ca2+ channel blocker. The antidepressant-like effects of both i.n. and intra-mPFC administrations of RvE1 were blocked by intra-mPFC infusion of a neutralizing antibody (nAb) for brain-derived neurotrophic factor (BDNF) or vascular endothelial growth factor (VEGF). Intra-mPFC infusion of rapamycin completely blocked the antidepressant-like effects of both i.n. and intra-mPFC administrations of RvE1 as well as those of intra-mPFC infusion of BDNF and VEGF. Moreover, i.n. RvE1 produced antidepressant-like effects via mTORC1 activation in the mPFC of a mouse model of repeated prednisolone-induced depression. Intra-dorsal DG infusion of BDNF and VEGF nAbs, but not rapamycin, blocked the antidepressant-like effects of i.n. RvE1. These findings suggest that i.n. administration of RvE1 produces antidepressant-like effects through activity-dependent BDNF/VEGF release in the mPFC and dorsal DG, and mTORC1 activation in the mPFC, but not in the dorsal DG. Thus, RvE1 can be a promising candidate for a novel rapid-acting antidepressant.