Diminished ovarian reserve(DOR)refers to a decrease in the number and/or quality of oocytes in the ovary,accompanied by a decline in reproductive potential,which is generally related to advanced age or ovarian disease...Diminished ovarian reserve(DOR)refers to a decrease in the number and/or quality of oocytes in the ovary,accompanied by a decline in reproductive potential,which is generally related to advanced age or ovarian disease.In in vitro fertilization(IVF)clinical practice,managing patients with DOR remains one of the most challenging tasks.In recent years,increased research on improving ovarian function has provided us with new insights into treating patients with DOR.Many therapeutic options have been proposed to improve the ovarian function of patients with DOR,yet they are not widely utilized in clinical practice because of limited evidence of safety and effectiveness.In this review,we focus on the mechanisms from animal models and clinical trials that have been applied to the treatment of DOR in recent years,intending to improve IVF outcomes in patients with DOR.Furthermore,new insights and perspectives on the molecular and cellular regulation of follicular development and ovarian reserve are emphasized to provide more clues for research on the treatment of DOR.展开更多
Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studie...Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs,including the ovary.The spatial and temporal expression of inhibin subunits(a,bA,bB,and bC),their cognate receptors,and activin-binding proteins(inhibins and follistatins)in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology.Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions,including primordial germ cell development,follicular growth and development,ovarian steroidogenesis,extracellular matrix remodeling,oocyte maturation,ovulation,and luteal function.Along with gonadotropins,intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature,competent oocyte that is prepared for fertilization.Abnormal activin expression,an imbalanced activin/follistatin ratio,and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies,such as reproductive aging,polycystic ovary syndrome,and ovarian cancers.Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.展开更多
Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements ...Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements in developmental biology techniq ues,this superior biomaterial has seen increasing utilization in 3D in vitro tissue culture.Three-dimensional cell cultures,often referred to as organoids,have emerged in response to technological advancements in biomaterials and the growing need in the field of medical research.They serve as important models for simulating normal physiological activities in vivo,addressing limitations in experimental material sources,and resolving ethical issues.In this review,we discuss the material characteristics of CBBs commonly used for organoid culture,integrating aspects such as Matrigel and decellularized ECM as culture matrices.We also analyzed the development prospects and directions of various materials in the context of biology,clinical medicine,and partic ularly reproductive medicine.Currently,despite the FDA approval and clinical research incorporating numerous CBBs,existing challenges in multiple studies indicate a significant unmet need in the development of key tissue models for both medical research and clinical applications.In summary,CBBs are swiftly broadening their applicability in the realms of organoid nature and medical research,serving as a versatile and high-performing material for 3D in vitro tissue culture.展开更多
基金the National Science Fund for Distinguished Young Scholars(No.81925013 to R.L.)。
文摘Diminished ovarian reserve(DOR)refers to a decrease in the number and/or quality of oocytes in the ovary,accompanied by a decline in reproductive potential,which is generally related to advanced age or ovarian disease.In in vitro fertilization(IVF)clinical practice,managing patients with DOR remains one of the most challenging tasks.In recent years,increased research on improving ovarian function has provided us with new insights into treating patients with DOR.Many therapeutic options have been proposed to improve the ovarian function of patients with DOR,yet they are not widely utilized in clinical practice because of limited evidence of safety and effectiveness.In this review,we focus on the mechanisms from animal models and clinical trials that have been applied to the treatment of DOR in recent years,intending to improve IVF outcomes in patients with DOR.Furthermore,new insights and perspectives on the molecular and cellular regulation of follicular development and ovarian reserve are emphasized to provide more clues for research on the treatment of DOR.
基金This work was supported by the Foundation Scheme Grant FDN-143317 to PCKL.
文摘Initially discovered in the pituitary as stimulators of follicle stimulating hormone,activins are homo-or heterodimers of inhibin subunits,which belong to the transforming growth factor-b superfamily.Subsequent studies have demonstrated that these growth factors play multifaceted roles in regulating various functions in multiple organs,including the ovary.The spatial and temporal expression of inhibin subunits(a,bA,bB,and bC),their cognate receptors,and activin-binding proteins(inhibins and follistatins)in the principal cells of growing follicles in human ovaries indicates that these activin isoforms are involved in ovarian biology.Information collected from animal studies and clinical samples suggests that these locally produced growth factors are crucial modulators of various ovarian functions,including primordial germ cell development,follicular growth and development,ovarian steroidogenesis,extracellular matrix remodeling,oocyte maturation,ovulation,and luteal function.Along with gonadotropins,intrafollicular activins exert synergistic and complementary effects on growing follicles to help them develop a mature,competent oocyte that is prepared for fertilization.Abnormal activin expression,an imbalanced activin/follistatin ratio,and the dysregulation of the activin signaling pathway have been observed in several ovarian pathologies,such as reproductive aging,polycystic ovary syndrome,and ovarian cancers.Recent advancements in our understanding of the molecular interactions and mechanisms that underlie activins and the development of related ovarian abnormalities have provided insights into disease pathogenesis and increased opportunities to achieve efficient and safe therapies.
基金supported by funding from the projects of the National Natural Science Foundation of China(Y.Z.,Grant No.82001496)Sichuan Science and Technology Program(Sichuan Natural Science Foundation for Youth,China,NO.2022NSFSC1281)Sichuan Medical Association Foundation(China,NO.S21006)
文摘Collagen-based biomaterials(CBB) are highly esteemed by researchers in materials science and biomedicine due to their extensive applications across various biomedical disciplines.In recent years,owing to advancements in developmental biology techniq ues,this superior biomaterial has seen increasing utilization in 3D in vitro tissue culture.Three-dimensional cell cultures,often referred to as organoids,have emerged in response to technological advancements in biomaterials and the growing need in the field of medical research.They serve as important models for simulating normal physiological activities in vivo,addressing limitations in experimental material sources,and resolving ethical issues.In this review,we discuss the material characteristics of CBBs commonly used for organoid culture,integrating aspects such as Matrigel and decellularized ECM as culture matrices.We also analyzed the development prospects and directions of various materials in the context of biology,clinical medicine,and partic ularly reproductive medicine.Currently,despite the FDA approval and clinical research incorporating numerous CBBs,existing challenges in multiple studies indicate a significant unmet need in the development of key tissue models for both medical research and clinical applications.In summary,CBBs are swiftly broadening their applicability in the realms of organoid nature and medical research,serving as a versatile and high-performing material for 3D in vitro tissue culture.