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Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

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… It suppresses GDF9 and BMP15 transcription, disrupts granulosa cells, and triggers lipid accumulation and mitochondrial injury. … Doxorubicin induces cytotoxicity and miR-132 expression in granulosa cells. …

Metastatic melanoma to the ovary in pregnancy: A case report.

Metastatic melanoma to the ovary is an uncommon presentation. We report a case of metastatic melanoma to the ovary that presented as a growing left adnexal mass during pregnancy and was thought to be benign by imaging and frozen section pathology. Here we discuss the challenges in radiologic and pathologic diagnosis, as well as considerations for the mother and newborn.

Existing and emerging strategies for fertility preservation in female patients with leukemia.

Leukemia, the most common malignancy in childhood, affects individuals from prepubertal girl to women of reproductive age. It originates from immature hematopoietic cells in the bone marrow and disseminates systemically via the blood and lymphatic circulations. Although survival rates have improved substantially, standard treatments, including intensive chemotherapy and hematopoietic stem cell transplantation, often combined with total body irradiation, are highly gonadotoxic. Consequently, a significant proportion of survivors experience long-term endocrine dysfunction and infertility, with f

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… In murine models of AML, leukemic cells have been shown to infiltrate ovarian tissue, particularly within the stromal compartment and among the granulosa cells of antral follicles. … The upper panel shows a healthy ovary with abundant healthy primordial follicles (PF; light pink), intact granulosa cells (GC), and a well-organized, branched healthy vasculature (red). …

[Effect of acupuncture on early embryos in poor ovarian response mice based on transcriptome sequencing].

OBJECTIVE: To observe the effect of "Zhibian" (BL54)-to-"Shuidao" (ST28) needling technique on the reproductive function of the mice with po … , elevated FSH and LH in the serum (P<0.01); more atresia follicles in ovarian tissue, disorganized granulosa cells, reduced the numbers of mitochondria, vacuoles appeared and cristae breakage. When compared with the model group, in the acupuncture group, the spirits of mice, food intake and activity were improved, the rate of estrous cycle disorder was reduced ( …

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… Simultaneously, granulosa cells deteriorate functionally, with heightened oxidative stress and diminished mitochondrial output, reducing their metabolic support for oocytes and establishing a self‐reinforcing cycle of ovarian decline [ 153 ]. … At the tissue level, the ovarian stroma stiffens progressively with age, disrupting granulosa cell–oocyte communication through aberrant mechanotransduction and impairing secondary follicular development [ 154 ]. …

Идентификация и проверка генов, связанных со старением, у пациентов с множественной миеломой.

Это исследование было направлено на выявление и проверку связанных со старением генов (ARGs), связанных с множественной миеломой (MM), что способствовало более глубокому пониманию молекулярных механизмов, лежащих в основе этого заболевания. Для изучения функциональных ролей ARG в MM были проведены генной онтологии и Киото-Энциклопедии по обогащению генов и геномов. Потенциальные гены, выявленные с помощью наименьшего абсолютного сокращения и селекционного оператора (LASSO) логистической регрессии и рекурсивного устранения векторных функций (SVM-RFE), были сопоставлены с помощью диаграммы Венна

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… The m6A mRNA demethylase FTO in granulosa cells can slow FOS-dependent ovarian aging ( 23 ). KCNA3 is implicated in cognitive aging ( 24 ). P53/HIF-1α regulates neuronal aging and autophagy in spinal cord ischemia/reperfusion injury ( 25 ). … cells retards FOS-dependent ovarian aging Cell Death Dis 12 744 2021 10.1038/s41419-021-04016-9 34315853 PMC8316443 24 Abdul Sani NF Amir Hamzah AIZ Abu Bakar ZH Mohd Yusof YA Makpol S Wan Ngah WZ Damanhuri HA Gene expression profile in different age groups and its association with cognitive function …

Иммуномодулирующие механизмы мезенхимальных ячеек: цитокинские сети и терапевтический потенциал через иммунные, воспаленные и регенеративные расстройства.

Мезенхимические стромальные клетки (МСЦ) представляют собой многопоточные клетки, характеризующиеся их регенеративной способностью и сильными иммунодуляторными свойствами. В последние годы терапия на базе МСЦ привлекла к себе значительное внимание в качестве потенциального средства лечения широкого круга иммунных и дегенеративных заболеваний. Терапевтические эффекты MSC главным образом получают через паракринную сигнализацию и секрецию цитокинов, которые регулируют иммунную реакцию и содействуют ремонту тканей. В настоящем обзоре основное внимание уделяется пяти ключевым цитокинам, участвующим

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… Mechanistically, MSCs reduce apoptosis of granulosa cells, enhance follicular development, and promote restoration of hormonal balance. … MSC-derived secretome, including growth factors such as IGF-1, VEGF, and hepatocyte growth factor (HGF), as well as exosomal microRNAs, promotes follicular survival, reduces granulosa cell apoptosis, stimulates angiogenesis, and contributes to restoration of hormonal balance. …

Spliced or Unspliced, That Is the Question: The Biological Roles of XBP1 Isoforms in Pathophysiology.

X-box binding protein 1 (XBP1) is a member of the CREB/ATF basic region leucine zipper family transcribed as the unspliced isoform (XBP1-u), which, upon exposure to endoplasmic reticulum stress, is spliced into its spliced isoform (XBP1-s). XBP1-s interacts with the cAMP response element of major histocompatibility complex class II gene and plays critical role in unfolded protein response (UPR) by regulating the transcriptional activity of genes involved in UPR. XBP1-s is also involved in other physiological pathways, including lipid metabolism, insulin metabolism, and differentiation of immun

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… XBP1-s is also crucial in regulating the estrus cycle and fertility by regulating the function of granulosa cells (GCs), which are key cells that promote follicular development by secreting estradiol. … Knockdown of XBP1 by RNAi in Mouse Granulosa Cells Promotes Apoptosis, Inhibits Cell Cycle, and Decreases Estradiol Synthesis Int. J. Mol. Sci. 2017 18 1152 10.3390/ijms18061152 28555054 PMC5485976 72. So J.S. Roles of Endoplasmic Reticulum Stress in Immune Responses Mol. …

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of

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… BMP-7 | ↑ pSmad1/5/9 (murine bone marrow mononuclear cells; 100 ng/mL) [ 59 ]; MAPK: ↑ pp38 (murine bone marrow mononuclear cells; 100 ng/mL) [ 59 ]; ↑ pSmad1/5 (rat and human granulosa cells; 100 ng/mL) [ 196 ]. | ↑ pSmad1/5 (C2C12 cells; 1000 ng/mL) [ 193 ]; ↑ pSmad1/5 (human embryonic stem cells; … BMPRIA (ALK3); BMPRIB (ALK6) | BMPRII | BMP-15 | ↑ pSmad1/5 (immortalized human granulosa cells and human granulosa cell tumor cells; 100 ng/mL) [ 198 ]; ↑ pSmad1/5 (rat and human granulosa cells; 100 ng/mL) [ 196 ]. | N.A. …

Мелатонин за пределами хронобиологии: интеграция фармакокинетики, прогнозирование дозы и клинические данные.

Мелатонин установлен в качестве регулятора времени и сна в циркадиане, в то время как более широкий спектр зависящих от рецептора и независимых от рецептора биологических эффектов вызвал интерес к дополнительным видам терапевтического применения. В этом обзоре критически рассматривается вопрос о том, можно ли интерпретировать эти предлагаемые последствия в фармакологических рамках, основанных на воздействии. Мы интегрируем недавние доклинические и клинические данные с фармакокинетиками перорального и внутривенного мелатонина и с обычным дифференциальном уравнением (ОДВ) - прогнозом воздействия

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… ; ovarian injury | Melatonin mitigated fetal-hypoxia-associated autophagic and mitochondrial impairment in ovarian granulosa cells. | Provides a mechanistic developmental/reproductive signal whose clinical relevance depends on exposure, developmental stage, and safety. [ 57 ] | Cancer / breast cancer … Zhang L, Liu K, Liu Z, Tao H, Fu X, Hou J, Jia G, Hou Y (2024) In pre-clinical study fetal hypoxia caused autophagy and mitochondrial impairment in ovary granulosa cells mitigated by melatonin supplement. J Adv Res 64:15–30. 10.1016/j.jare.2023.11.008 37. …

The Impact of Histone Modifications in Endometriosis Highlights New Therapeutic Opportunities.

Endometriosis is a chronic disorder of the female reproductive system which afflicts a great number of women worldwide. Histone deacetylases (HDACs) prevent the relaxation of chromatin, thereby positively or negatively modulating gene transcription. The current review aims at studying the impact of histone modifications and their therapeutic targeting in endometriosis. In order to identify relevant studies, a literature review was conducted using the MEDLINE and LIVIVO databases. The current manuscript represents the most comprehensive, up-to-date review of the literature focusing on the parti

The crosstalk between non-coding RNAs and oxidative stress in cancer progression.

As living standards elevate, cancers are appearing in growing numbers among younger individuals globally and these risks escalate with advancing years. One of the reasons is that instability in the cancer genome reduces the effectiveness of conventional drug treatments and chemotherapy, compared with more targeted therapies. Previous research has discovered non-coding RNAs' crucial role in shaping genetic networks involved in cancer cell growth and invasion through their influence on messenger RNA production or protein binding. Additionally, the interaction between non-coding RNAs and oxidativ

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… cells from oxidative stress-induced apoptosis by targeting KLF4 in the H 2 O 2 -induced in vitro model and 3-NP-induced in vivo ovarian oxidative stress model to maintain normal ovarian function. 90 In breast cancer cell lines, miR-145 directly interferes with the Ang2 gene translation and its expression … MicroRNA-145 protects follicular granulosa cells against oxidative stress-induced apoptosis by targeting Krüppel-like factor 4. Mol Cell Endocrinol. 2017;452:138–147. doi: 10.1016/j.mce.2017.05.030. 91. Liu S.Y., Li X.Y., Chen W.Q., et al. …

More Than an Adipokine: The Complex Roles of Chemerin Signaling in Cancer.

Chemerin is widely recognized as an adipokine, with diverse biological roles in cellular differentiation and metabolism, as well as a leukocyte chemoattractant. Research investigating the role of chemerin in the obesity-cancer relationship has provided evidence both for pro- and anti-cancer effects. The tumor-promoting effects of chemerin primarily involve direct effects on migration, invasion, and metastasis as well as growth and proliferation of cancer cells. Chemerin can also promote tumor growth via the recruitment of tumor-supporting mesenchymal stromal cells and stimulation of angiogenes

Utilization of Stem Cells in Medicine: A Narrative Review.

Regenerative medicine holds significant promise for addressing diseases and irreversible damage that are challenging to treat with conventional methods, making it a prominent research focus in modern medicine. Research on stem cells, a key area within regenerative medicine due to their self-renewal capabilities, is expanding, positioning them as a novel therapeutic option. Stem cells, utilized in various treatments, are categorized based on their differentiation potential and the source tissue. The term 'stem cell' encompasses a broad spectrum of cells, which can be derived from embryonic tiss

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… Granulosa cells, which are imperative in female fertility, have been explored in animal models. Stem cells from amniotic fluid have demonstrated the ability to differentiate into granulosa cells and improve overall follicular health [ 138 ]. … Interestingly, micro-RNA isolated from stem cells has also shown to blunt apoptosis of granulosa cells and improve survival of ovarian follicles following chemotherapy [ 139 ]. …

Granular assessment of paediatric and adolescent ovaries following low levels of alkylating treatment reveals significant morphologic differences in early stage follicles.

STUDY QUESTION: Are subtle changes in the paediatric adolescent/young adult ovarian follicles and microenvironment following low-dose acute alkylating chemotherapy detectable by granular assessment tools? SUMMARY ANSWER: Low-dose alkylating agents impact the ovaries of pre- and post-pubertal participants with significant alterations to the follicle and oocyte area, number of granulosa cells (GCs) per follicle, and number of immature vessels, when compared to ovaries from untreated participants. WHAT IS KNOWN ALREADY: The metric known as cyclophosphamide equivalent dose (CED) was developed to…

Pre-treatment AMH levels suggesting PCOM do not prevent chemotherapy-induced ovarian damage despite higher long-term ovarian reserve: a longitudinal study in 467 women treated with alkylating agents.

STUDY QUESTION: Are young women with anti-Müllerian hormone (AMH) levels suggesting polycystic ovarian morphology (PCOM) at baseline better … High AMH levels in women with polycystic ovaries have been associated with decreasing apoptosis of granulosa cells in small follicles and altered initial follicular growth. STUDY DESIGN, SIZE, DURATION: This retrospective analysis of prospective collected data was carried out at the OncoFertility Observatory of the Lille University Hospital from January 2012 to …

Keyword Index for Volume 109

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Fertility Preservation in Female Patients with Cancer. Part I: Challenges and Future Prospects in Developing Countries; A Narrative Review Study.

While international guidelines on oncofertility practice have been published in developed countries, there is limited information available on oncofertility practice in developing countries, which often face limitations in their cancer health support networks. As survival rates improve in the field of cancer and other diseases, there is a growing need for stronger oncofertility services in developing countries. Given that 50% of cancer patients are under the age of 65, many of these patients are of reproductive age and preserving their fertility health prior to starting treatment is valuable.

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… These agents destroy ovarian follicles and granulosa cells, as well as oocytes ( 15 ). The damage caused by these agents is related to the dose, drug type, and duration of treatment and increases with age. … Compared to IVF, this procedure may increase the risk of blood contamination which entails simultaneous aspiration and needle-forced detachment of granulosa cells from the small antral follicles. …

Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane.

Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide. Stimulation of HPMCs with IL-6 in co

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… IL-6 promotes FSH-induced VEGF expression through JAK/STAT3 signaling pathway in bovine granulosa cells . Cell. Physiol. Biochem. 44 , 293 – 302 . 10.1159/000484885 , PMID: 29132131 Zhang S. Li M. Gu Y. Liu Z. Xu S. Cui Y. . ( 2008 ). …

Case report: Therapeutic use of bortezomib in a patient with Schnitzler syndrome.

Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disorder, characterized by chronic urticarial rash and immunoglobulin M (IgM) monoclonal gammopathy. Anti-interleukin-1 (IL-1) therapies have been shown to be more effective in managing the clinical symptoms of SchS compared to anti-IL-6 therapies. In this case report, we present a male patient with urticarial rash, fever, and arthralgia. Laboratory tests identified the presence of IgMκ monoclonal protein, and the absence of IL-1β in serum. Whole exome sequencing (WES) did not reveal any pathological variants associated wi

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… IL-1α Up-regulates IL-6 expression in bovine granulosa cells via MAPKs and NF-κB signaling pathways. Cell Physiol Biochem. (2017) 41:265–73. doi: 10.1159/000456091 50. Fang F, Lan XX, Hu RH, et al. …