Maintenance Of Organs Research Articles

Normothermic Machine Perfusion in Orphan Liver Graft Viability Assessment

Background: Liver transplantation constitutes a well-established treatment for patients with end-stage liver disease and selected hepatic malignancies. The introduction of normothermic machine perfusion (NMP) offers a platform for both extracorporeal organ maintenance and viability assessment, especially for organs with suspicious malfunction. These organs, discarded by the majority of transplant centers (so-called ‘orphan livers’), may help to safely expand the donor pool thanks to pre-transplant appraisal; Methods: We identified all grafts undergoing normothermic ma-chine perfusions performed in the Department of General, Transplant, and Liver Surgery between December 2022 and August 2023. Their perfusion characteristics and immediate postoperative periods, as well as complications that occurred in the 90-day postoperative periods, were analyzed; Results: There were eight orphan liver grafts that underwent NMP in our Department. Postoperative complications occurring in patients receiving grafts after NMP did not seem associated with the procedure. One patient required laparotomy within the 90-day postoperative period due to biliary fistula and underwent bile duct stenting due to both fistula and nonanastomotic stricture. In one patient we observed the occurrence of anastomotic biliary stricture more than 90 days after LTx; Conclusions: NMP allows for the viability assessment of grafts with suspicious prepreservation malfunction. Some of these organs may help to expand the donor pool.

The Era of Risk Factors Should End; the Era of Biologic Age Should Begin

Introduction: Risk factors, a 75-year-old concept, are instrumental in the management of the general population. Newer biomarkers can explain residual risk and protection from risk. The population needs a new platform to make more comprehensible the importance of managing risk. Biologic age, the number of years left to live, is the platform that will receive the attention of patients. Method: Risk factor odds ratios are used to approximate the years lost to the modifiable risk, calculating a biologic age. Newer biomarkers confirm the predication and can be used to explain the pleomorphic properties of medications and unrealized risk. The biomarkers represent the following biologic processes: repair, inflammation, immune function, hematologic, clotting factors, metabolic-nutritional, organ maintenance, anthropomorphic, environmental, endothelial function, sleep, co-morbidities, frailty, and electromagnetic. Risk factors and biomarkers are ranked in the order of significance in reducing biologic age. Results: A six-step method of patient management using biologic age and biomarkers is presented. Conclusions: Knowledge of risk factors and therapies to improve risk has increased over the last 75 years. Biologic age is more appropriate in explaining the significance of this knowledge and may improve patient compliance to lifestyle changes and medication compliance. Appropriate counseling with utilization of biomarkers of biologic processes, such as high sensitivity-CRP, circulating stem cells, number of co-morbidities, frailty, electrocardiogram, and pulse wave velocity will improve compliance and personalize care. The 6-minute walk should be incorporated into the vital signs due to prognostic significance.

Unusual modes of cell and nuclear divisions characterise Drosophila development.

The growth and development of metazoan organisms is dependent upon a co-ordinated programme of cellular proliferation and differentiation, from the initial formation of the zygote through to maintenance of mature organs in adult organisms. Early studies of proliferation of ex vivo cultures and unicellular eukaryotes described a cyclic nature of cell division characterised by periods of DNA synthesis (S-phase) and segregation of newly synthesized chromosomes (M-phase) interspersed by seeming inactivity, the gap phases, G1 and G2. We now know that G1 and G2 play critical roles in regulating the cell cycle, including monitoring of favourable environmental conditions to facilitate cell division, and ensuring genomic integrity prior to DNA replication and nuclear division. M-phase is usually followed by the physical separation of nascent daughters, termed cytokinesis. These phases where G1 leads to S phase, followed by G2 prior to M phase and the subsequent cytokinesis to produce two daughters, both identical in genomic composition and cellular morphology are what might be termed an archetypal cell division. Studies of development of many different organs in different species have demonstrated that this stereotypical cell cycle is often subverted to produce specific developmental outcomes, and examples from over 100 years of analysis of the development of Drosophila melanogaster have uncovered many different modes of cell division within this one species.

The Wilms' Tumor Suppressor WT1 in Cardiomyocytes: Implications for Cardiac Homeostasis and Repair.

The Wilms' tumor suppressor WT1 is essential for the development of the heart, among other organs such as the kidneys and gonads. The Wt1 gene encodes a zinc finger transcription factor that regulates proliferation, cellular differentiation processes, and apoptosis. WT1 is also involved in cardiac homeostasis and repair. In adulthood, WT1-expression levels are lower compared to those observed through development, and WT1 expression is restricted to a few cell types. However, its systemic deletion in adult mice is lethal, demonstrating that its presence is also key for organ maintenance. In response to injury, the epicardium re-activates the expression of WT1, but little is known about the roles it plays in cardiomyocytes, which are the main cell type affected after myocardial infarction. The fact that cardiomyocytes exhibit a low proliferation rate in the adult heart in mammals highlights the need to explore new approaches for cardiac regeneration. The aim of this review is to emphasize the functions carried out by WT1 in cardiomyocytes in cardiac homeostasis and heart regeneration.

The "Culture" of Organs: A Holistic Theory on the Origins of the Cancer Tissue Environment.

For over a century, the somatic gene mutation theory of cancer has been a scientific orthodoxy. The recent failures of causal explanations using this theory and the lack of significant progress in addressing the cancer problem medically have led to a new competition of ideas about just what cancer is. This essay presents an alternative view of cancer as a developmental process gone wrong. More specifically, cancer is a breakdown in the autopoietic process of organ maintenance and the multicellular coordination of tissues. Breast cancer is viewed through a systems science perspective as an example of the importance of framing one's theoretical assumptions before making empirical judgments. Finally, a new understanding of the histoarchitecture of the interstitium is presented as a first principle of cancer: a process of cells coming from cells, invading the space between cells.

Observation of E-cadherin adherens junction dynamics with metal-induced energy transfer imaging and spectroscopy

Epithelial cadherin (E-cad) mediated cell-cell junctions play a crucial role in the establishment and maintenance of tissues and organs. In this study, we employed metal-induced energy transfer imaging and spectroscopy to investigate variations in intermembrane distance during adhesion between two model membranes adorned with E-cad. By correlating the measured intermembrane distances with the distinct E-cad junction states, we probed the dynamic behavior and diversity of E-cad junctions across different binding pathways. Our observations led to the identification of a transient intermediate state referred to as the X-dimeric state and enabled a detailed analysis of its kinetics. We discovered that the formation of the X-dimer leads to significant membrane displacement, subsequently impacting the formation of other X-dimers. These direct experimental insights into the subtle dynamics of E-cad-modified membranes and the resultant changes in intermembrane distance provide perspectives on the assembly of E-cad junctions between cells. This knowledge enhances our comprehension of tissue and organ development and may serve as a foundation for the development of innovative therapeutic strategies for diseases linked to cell-cell adhesion abnormalities.

Sea food by-products valorization for biomedical applications: evaluation of their wound regeneration capabilities in an Ex vivo skin model.

The skin is often exposed to harmful stimuli that might compromise its integrity and functionality. After an injury, the skin has a limited capability to restore its complex structure, and in the case of severe skin damage, surgical operations and rapid application of wound dressings are often required to promote optimal wound healing. Nowadays, collagen-based biomaterials are widely used in combination with bioactive molecules able to prevent excessive inflammation and possible infections. In line with a circular economy and blue biotechnology approach, it was recently demonstrated that both collagen and bioactive molecules (i.e., antioxidant compounds) can be sustainably obtained from sea food by-products and effectively used for biomaterial development. Herein, we describe and compare the application of two marine collagen-based wound dressings (CBWDs), produced with materials obtained from sea urchin food waste, for the treatment of skin lesions in a wound healing organ culture (WHOC) model. The ex vivo WHOC model was set up starting from rat skin explants and the induced lesions were assigned into three different groups: control (CTRL) group, not treated, marine collagen wound dressing (MCWD) group, and antioxidants-enriched marine collagen wound dressing (A-MCWD) group. After 5 and 10 days, specimens were examined for organ maintenance and assessed for the healing process. Immunohistochemical results showed that both CBWDs were similarly successful in prolonging skin repair, preserving the epidermal barrier up to 5 days under static culture conditions. Histological and gene expression analysis highlighted that the A-MCWD might support and accelerate skin wound healing by exerting antioxidant activity and counteracting inflammation. Overall, these findings underline the potential of sea urchin food waste as a novel resource for the development of functional medical devices for the treatment of skin wounds.

An adaptive numerical method for multi-cellular simulations of tissue development and maintenance

In recent years, multi-cellular models, where cells are represented as individual interacting entities, are becoming ever popular. This has led to a proliferation of novel methods and simulation tools. The first aim of this paper is to review the numerical methods utilised by multi-cellular modelling tools and to demonstrate which numerical methods are appropriate for simulations of tissue and organ development, maintenance, and disease. The second aim is to introduce an adaptive time-stepping algorithm and to demonstrate it’s efficiency and accuracy. We focus on off-lattice, mechanics based, models where cell movement is defined by a series of first order ordinary differential equations, derived by assuming over-damped motion and balancing forces. We see that many numerical methods have been used, ranging from simple Forward Euler approaches through to higher order single-step methods like Runge–Kutta 4 and multi-step methods like Adams–Bashforth 2. Through a series of exemplar multi-cellular simulations, we see that if: care is taken to have events (births deaths and re-meshing/re-arrangements) occur on common time-steps; and boundaries are imposed on all sub-steps of numerical methods or implemented using forces, then all numerical methods can converge with the correct order. We introduce an adaptive time-stepping method and demonstrate that the best compromise between L∞ error and run-time is to use Runge–Kutta 4 with an increased time-step and moderate adaptivity. We see that a judicious choice of numerical method can speed the simulation up by a factor of 10–60 from the Forward Euler methods seen in Osborne et al. (2017), and a further speed up by a factor of 4 can be achieved by using an adaptive time-step.

Rab11 maintains the undifferentiated state of adult midgut precursors via DPP pathway

Asymmetric stem cell divisions play instrumental roles in the maintenance, growth and differentiation of organs. Failure of asymmetric stem cell divisions may result in an array of developmental disorders, including cancer. It is well established that the gene, inscuteable, acts as the upstream component of asymmetric cell divisions. In Drosophila larval midgut, a founder adult midgut precursor (AMP) experiences an asymmetric division to instruct its first daughter to become a peripheral cell that serves as a niche where the AMP and its future daughters can remain undifferentiated.The present study demonstrates that inscuteable expressing stem cells require Rab11, a conserved small Ras-like GTPase, for proper proliferation and differentiation. As insc-GAL4 mediated Rab11RNAi in Drosophila larval and adult midguts show the disruption of the niche microenvironment of adult midgut precursors as well as elevated DPP signalling at the larval stage, which is associated with aberrant over-proliferation and early differentiation of larval AMPs and adult intestinal stem cells. The observed connections between Rab11, larval AMP proliferation, niche establishment, and DPP signalling highlight the potential for Rab11 to serve as a key regulatory factor in maintaining tissue homeostasis and balanced cellular growth.

ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels.

Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels. It has been reported recently that some EC populations possess higher clonal proliferative potential and vessel-forming capacity compared with mature ECs. Nevertheless, a marker to identify vascular clonal repopulating ECs (CRECs) in murine and human individuals is lacking, and, hence, the mechanism for the proliferative, self-renewal, and vessel-forming potential of CRECs is elusive. We analyzed colony-forming, self-renewal, and vessel-forming potential of ABCG2 (ATP binding cassette subfamily G member 2)-expressing ECs in human umbilical vessels. To study the contribution of Abcg2-expressing ECs to vessel development and regeneration, we developed Abcg2CreErt2;ROSA TdTomato mice and performed lineage tracing during mouse development and during tissue regeneration after myocardial infarction injury. RNA sequencing and chromatin methylation chromatin immunoprecipitation followed by sequencing were conducted to study the gene regulation in Abcg2-expressing ECs. In human and mouse vessels, ECs with higher ABCG2 expression (ABCECs) possess higher clonal proliferative potential and in vivo vessel-forming potential compared with mature ECs. These cells could clonally contribute to vessel formation in primary and secondary recipients after transplantation. These features of ABCECs meet the criteria of CRECs. Results from lineage tracing experiments confirm that Abcg2-expressing CRECs (AbcCRECs) contribute to arteries, veins, and capillaries in cardiac tissue development and vascular tissue regeneration after myocardial infarction. Transcriptome and epigenetic analyses reveal that a gene expression signature involved in angiogenesis and vessel development is enriched in AbcCRECs. In addition, various angiogenic genes, such as Notch2 and Hey2, are bivalently modified by trimethylation at the 4th and 27th lysine residue of histone H3 (H3K4me3 and H3K27me3) in AbcCRECs. These results are the first to establish that a single prospective marker identifies CRECs in mice and human individuals, which holds promise to provide new cell therapies for repair of damaged vessels in patients with endothelial dysfunction.

Influence Factors of Reproductive Organ Maintenance Among Adolescent Girls in Coastal Areas

Adolescent girls are vulnerable to reproductive health problems such as vaginal discharge and reproductive tract infections, which are triggered by poor maintenance of their reproductive organs. This may further impact adolescents' quality of life and productivity. Adolescents in coastal areas tend to have limited sources of information, parental support, and inadequate health facilities related to adolescent reproductive health. This study aims to determine the factors that influence the behavior of maintaining reproductive organs among adolescent girls in coastal areas in the Buluspesantren District. Method: This research uses quantitative methods with a cross-sectional approach. The research population was 859 adolescent girls in coastal regions of Buluspesantren District, and a total sample of 96 respondents were selected through purposive sampling. Data were analyzed univariate, bivariate, and multivariate. There is a relationship between the availability of facilities and infrastructure (p-value=0.049) and attitudes (p-value=0.012) with reproductive organ maintenance behavior among adolescent girls in coastal areas in Buluspesantren District. The most influential factor is attitude (p-value = 0.018) with Odds Ratio (OR)=3.004. Adolescent girls with a positive attitude are 3.004 times more likely to have good reproductive organ maintenance behavior than adolescent girls with a negative attitude. Adolescent girls need to get information on reproductive organ maintenance from various trusted sources so that they have a positive attitude toward reproductive organ maintenance behavior.

The noncanonical NFκB pathway: Regulatory mechanisms in health and disease.

The noncanonical NFκB signaling pathway mediates the biological functions of diverse cell survival, growth, maturation, and differentiation factors that are important for the development and maintenance of hematopoietic cells and immune organs. Its dysregulation is associated with a number of immune pathologies and malignancies. Originally described as the signaling pathway that controls the NFκB family member RelB, we now know that noncanonical signaling also controls NFκB RelA and cRel. Here, we aim to clarify our understanding of the molecular network that mediates noncanonical NFκB signaling and review the human diseases that result from a deficient or hyper-active noncanonical NFκB pathway. It turns out that dysregulation of RelA and cRel, not RelB, is often implicated in mediating the resulting pathology. This article is categorized under: Immune System Diseases > Molecular and Cellular Physiology Cancer > Molecular and Cellular Physiology Immune System Diseases > Stem Cells and Development.

Ultrasound Morphometry of the Pelvic Floor Muscles in Women of Reproductive Age

Biometric studies in nulliparous women conducted to date are limited by small sample sizes. The pelvic floor muscles perform an important function throughout a woman’s life. They provide fixation and maintenance of the pelvic organs, stretches during childbirth, ensuring the formation of the birth canal, and are a potential site for the formation of a hernia in the female body. Impaired function of this muscle group can lead to either excessive muscle contraction (chronic pelvic pain syndrome) or excessive stretching (pelvic organ prolapse). The purpose of the study is to assess the morphometric properties of the pelvic floor muscles in nulliparous women using 3D ultrasound scanning (sonography). Material and methods. The observation group consisted of 60 women of middle reproductive age who applied for an appointment with an obstetriciangynecologist with complaints of pain of various types localized in the perineum and pelvis, decreased desire and quality of sexual life, clinically confirmed by a diagnosis of incompetence of the pelvic floor muscles. The control group consisted of 30 women without dysfunction of the pelvic floor muscles according to clinical examination. The main criterion for inclusion of patients in the study was reproductive age - 18–45 years and natural childbirth in obstetric and gynecological history. Results. We found that the absence of visible sonographic markers of changes in the myofascial structures of the pelvis is not a prognostically significant criterion for muscle dysfunction, since predominantly changes in morphometric parameters are a reliable sign of the formation of pelvic floor muscle failure. Conclusion. The ultrasound morphometry method, which allows one to assess dynamic changes in the size of muscle and fascial structures, can be used in the clinical practice of an obstetrician-gynecologist. Early diagnosis of a violation of the structure of pelvis myofascial complex will allow early implementation of measures aimed at prevention and timely treatment.

Role of steroid hormones in the maintenance of focal adhesions in bovine oviductal epithelial cells

The oviduct, the organ of the female reproductive system where fertilization and early embryonic development occur, provides an optimal environment for the final maturation of oocytes, storage, and sperm capacitation and transport of gametes and embryos. During the estrous cycle, the oviduct is affected by ovarian sex hormones, resulting in changes aimed at maintaining an appropriate microenvironment. Normal cell migration is tightly regulated, its role being essential for the development and maintenance of organ and tissue functions as well as for regeneration following injury. Due to their involvement in focal contact formations, focal adhesion kinase (PTK2) and paxillin (PXN) are key proteins in the study of cell migration and adhesion. The objective of this work was to compare the expression of PTK2 and PXN in oviductal cells along the estrous cycle and to determine if their expression is regulated by the presence of 17-β estradiol (E2) and/or progesterone (P4). No transcripts of PTK2 or of PXN were detected in cells corresponding to the luteal phase. Additionally, hormonal stimulation experiments on bovine oviductal cell cultures (BOECs) were carried out, where P4 inhibited the expression of both genes. Migration assays demonstrated that P4 reduced BOECs migration capacity. P4 treatment also reduced cell adhesion, while E2 increased the number of adhered cells. In conclusion, the presence of E2 and P4 regulates the expression of genes involved in the formation of focal contacts and modifies the migration and adhesion of BOECs. Understanding the effect of steroid hormones on BOECs is critical to grasp the impact of steroid control on oviductal function and its contribution to establishing successful pregnancies.

The Birth and Death of Floral Organs in Cereal Crops.

Florets of cereal crops are the basic reproductive organs that produce grains for food or feed. The birth of a floret progresses through meristem initiation and floral organ identity specification and maintenance. During these processes, both endogenous and external cues can trigger a premature floral organ death, leading to reproductive failure. Recent advances in different cereal crops have identified both conserved and distinct regulators governing the birth of a floret. However, the molecular underpinnings of floral death are just beginning to be understood. In this review, we first provide a general overview of the current findings in the field of floral development in major cereals and outline different forms of floral deaths, particularly in the Triticeae crops. We then highlight the importance of vascular patterning and photosynthesis in floral development and reproductive success and argue for an expanded knowledge of floral birth-death balance in the context of agroecology.

DINAMIKA PENDIDIKAN KESEHATAN DENGAN VIDEO ANIMASI TERHADAP PENGETAHUAN PEMELIHARAAN ORGAN REPRODUKSI DAN PENCEGAHAN SEX ABUSE PADA ANAK USIA SEKOLAH

Knowledge of maintaining reproductive organs and preventing sex abuse in school-age children has a very important role in helping their knowledge about maintaining their reproductive health and preventing sexual crimes. Experimental with pre-test and post-test using animated videos. The sampling technique used was total sampling (32 respondents) class VIII-H at SMPN 9 Gresik. Data were collected using a knowledge questionnaire on maintaining reproductive organs and preventing sex abuse. Average knowledge before being given health education (52.02) and after being given health education (75.91). The average understanding of preventing sex abuse before being given health education (70.31) and after being given health education (82.50). The results of the paired t-test showed the influence of health education (animated videos) on knowledge of reproductive organ maintenance and preventing sex abuse at school age (pvalue 0.000). There is an influence of animated videos on knowledge of maintaining reproductive organs and preventing sex abuse in school-aged children at SMPN 9 Gresik.

Development of Sexual Education Animation Videos to Improve Sexual Understanding and Understanding of Forms of Sexual Harassment Behavior of Yogyakarta Elementary School Students

Sexual education has a crucial role in providing understanding to children about reproductive organs, prevention of sexual violence, and maintenance of intimate organs. This study aims to develop learning media in the form of sexual education animation videos to improve sexual understanding and understanding of forms of sexual harassment behavior in elementary schools. ADDIE research and development methods (Analysis, Design, Development, Implementation, and Evaluation) are used in this product development process. Needs analysis was conducted through interviews with guidance and counseling teachers, as well as classroom teachers in several elementary schools in Yogyakarta. The development phase involves material design, animation video creation, validation by media experts and material experts, as well as field trials. Evaluation is carried out to correct product deficiencies before they are widely implemented. The development results include animated sexual education videos that received "very decent" validation from media experts and material experts. Field trials involved grade V students with results that showed increased sexual understanding and understanding of forms of sexual harassment behavior in classes that used animated videos compared to control classes. The teacher's response to the media shows a high level of practicality. In conclusion, this sexual education animation video is considered feasible, practical, and effective in increasing students' understanding of sexual material and forms of sexual harassment behavior in elementary schools. This media is expected to help teachers in providing appropriate, interesting, and appropriate sexual education according to the needs of elementary school-age children.

Genome-wide identification and structural analysis of the BMP gene family in Triplophysa dalaica.

Bone morphogenetic proteins (BMPs) are part of the transforming growth factor beta (TGF-β) superfamily and play crucial roles in bone development, as well as in the formation and maintenance of various organs. Triplophysa dalaica, a small loach fish that primarily inhabits relatively high elevations and cooler water bodies, was the focus of this study. Understanding the function of BMP genes during the morphogenesis of T. dalaica helps to clarify the mechanisms of its evolution and serves as a reference for the study of BMP genes in other bony fishes. The data for the T. dalaica transcriptome and genome used in this investigation were derived from the outcomes of our laboratory sequencing. This study identified a total of 26 BMP genes, all of which, except for BMP1, possess similar TGF-β structural domains. We conducted an analysis of these 26 BMP genes, examining their physicochemical properties, subcellular localization, phylogenetic relationships, covariance within and among species, chromosomal localization, gene structure, conserved motifs, conserved structural domains, and expression patterns. Our findings indicated that three BMP genes were associated with unstable proteins, while 11 BMP genes were located within the extracellular matrix. Furthermore, some BMP genes were duplicated, with the majority being enriched in the GO:0008083 pathway, which is related to growth factor activity. It was hypothesized that genes within the BMP1/3/11/15 subgroup (Group I) play a significant role in the growth and development of T. dalaica. By analyzing the expression patterns of proteins in nine tissues (gonad, kidney, gill, spleen, brain, liver, fin, heart, and muscle), we found that BMP genes play diverse regulatory roles during different stages of growth and development and exhibit characteristics of division of labor. This study contributes to a deeper understanding of BMP gene family member expression patterns in high-altitude, high-salinity environments and provides valuable insights for future research on the BMP gene family in bony fishes.

Results validation by using finite volume method for the blood flow with magnetohydrodynamics and hybrid nanofluids

This paper conducts an extensive comparative analysis of numerical methods employed in modeling blood flow through arteries with Magnetohydrodynamics (MHD) and hybrid nanofluids. The study investigates the effectiveness and precision of distinct numerical approaches: Akbari Ganji’s Method (AGM), Fourth-Order Runge–Kutta (RK4), Finite Volume Method (FVM), and the Finite Element Method (FEM). These methods are essential for comprehending the intricate fluid dynamics that arise in the presence of magnetic fields and hybrid nanofluids a phenomenon relevant in numerous medical applications. Blood flow is subjected to a homogeneous magnetic field in a radial direction while the magneto-hemodynamics effect is taken into account. A variety of medical, physiological, and surgical procedures, as well as the regulation of blood pressure, heat distribution, wound healing, diagnostic imaging, and drug discovery, depend on blood flow through arteries to carry out vital functions such as oxygen and nutrition delivery, organ maintenance, and wound healing. Our findings highlight that while each method has strengths, their applicability varies based on the problem’s characteristics and computational resource constraints. This analysis aids researchers and practitioners in selecting the most suitable method for their modeling requirements, advancing numerical techniques for complex fluid dynamics involving MHD and hybrid nanofluids.

Mesenchymal stem cell-derived apoptotic vesicles ameliorate impaired ovarian folliculogenesis in polycystic ovary syndrome and ovarian aging by targeting WNT signaling.

Rationale: It has been emergingly recognized that apoptosis generates plenty of heterogeneous apoptotic vesicles (apoVs), which play a pivotal role in the maintenance of organ and tissue homeostasis. However, it is unknown whether apoVs influence postnatal ovarian folliculogenesis. Methods: Apoptotic pathway deficient mice including Fas mutant (Fasmut ) and Fas ligand mutant (FasLmut ) mice were used with apoV replenishment to evaluate the biological function of apoVs during ovarian folliculogenesis. Ovarian function was characterized by morphological analysis, biochemical examination and cellular assays. Mechanistical studies were assessed by combinations of transcriptomic and proteomic analysis as well as molecular assays. CYP17A1-Cre; Axin1fl /fl mice was established to verify the role of WNT signaling during ovarian folliculogenesis. Polycystic ovarian syndrome (PCOS) mice and 15-month-old mice were used with apoV replenishment to further validate the therapeutic effects of apoVs based on WNT signaling regulation. Results: We show that systemic administration of mesenchymal stem cell (MSC)-derived apoptotic vesicles (MSC-apoVs) can ameliorate impaired ovarian folliculogenesis, PCOS phenotype, and reduced birth rate in Fasmut and FasLmut mice. Mechanistically, transcriptome analysis results revealed that MSC-apoVs downregulated a number of aberrant gene expression in Fasmut mice, which were enriched by kyoto encyclopedia of genes and genomes (KEGG) pathway analysis in WNT signaling and sex hormone biosynthesis. Furthermore, we found that apoptotic deficiency resulted in aberrant WNT/β-catenin activation in theca and mural granulosa cells, leading to responsive action of dickkopf1 (DKK1) in the cumulus cell and oocyte zone, which downregulated WNT/β-catenin expression in oocytes and, therefore, impaired ovarian folliculogenesis via NPPC/cGMP/PDE3A/cAMP cascade. When WNT/β-catenin was specially activated in theca cells of CYP17A1-Cre; Axin1fl /fl mice, the same ovarian impairment phenotypes observed in apoptosis-deficient mice were established, confirming that aberrant activation of WNT/β-catenin in theca cells caused the impairment of ovarian folliculogenesis. We firstly revealed that apoVs delivered WNT membrane receptor inhibitor protein RNF43 to ovarian theca cells to balance follicle homeostasis through vesicle-cell membrane integration. Systemically infused RNF43-apoVs down-regulated aberrantly activated WNT/β-catenin signaling in theca cells, contributing to ovarian functional maintenance. Since aging mice have down-regulated expression of WNT/β-catenin in oocytes, we used MSC-apoVs to treat 15-month-old mice and found that MSC-apoVs effectively ameliorated the ovarian function and fertility capacity of these aging mice through rescuing WNT/β-catenin expression in oocytes. Conclusion: Our studies reveal a previously unknown association between apoVs and ovarian folliculogenesis and suggest an apoV-based therapeutic approach to improve oocyte function and birth rates in PCOS and aging.