Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.
Female ; Humans ; Oogenesis/physiology* ; Granulosa Cells ; Extracellular Vesicles/physiology* ; Cell Communication ; RNA, Untranslated ; Infertility

The development of female germ cells can be mainly divided into two stages: fetal germ cells and oocytes in folliculogenesis after puberty. Mitosis-meiosis transition, meiosis arrest and re-activation are the key phases of the development. Several phases may be characterized by their distinct molecular events, which involve precise regulation of gene expression and interaction with corresponding gonadal niche cells. In recent years, single-cell transcriptome studies have clarified phase-specific patterns of gene expression, signaling pathways and epigenetic modification during oogenesis and folliculogenesis. These works have provided important insights into the development of female germ cells and pathogenesis of germ-cell related diseases, which may promote clinical application of reproductive genetic research.
Female ; Germ Cells ; Humans ; Meiosis ; Oocytes ; Oogenesis/genetics* ; Signal Transduction

Cyclic adenosine monophosphate (cAMP) is one of the significant and conserved second messengers in mammals, and it participates in regulating the developmental and physiological functions of various organs and tissues through transducting extracellular signals. Studies have shown that the process of meiosis in female mammalian oocytes is closely related to the level of cAMP and strictly regulated. In oocytes, cAMP is mainly synthesized by adenylate cyclase 3 (AC3) and degraded by phosphodiesterase 3A (PDE3A), both of which jointly regulate the level of cAMP in oocytes and play important roles in the follicular development and oogenesis of female ovaries. It has been well illuminated that high level of cAMP in the cytoplasm of oocytes in growing follicles could maintain the arrest of the first meiotic of oocytes for a long time. The oocytes will resume meiosis and mature either when the synthesis of cAMP is down-regulated, or when cAMP is degraded by PDE3A. In recent years, the novo physiological functions of cAMP in oogenesis have been reported. To better understand the regulatory role and mechanism of cAMP in mammalian gametogenesis, this paper reviews the relevant research regarding the relationship between cAMP and germ cell development.
Adenosine Monophosphate ; Animals ; Cyclic AMP ; Female ; Mammals ; Meiosis ; Oocytes ; Oogenesis

Oogenesis is the basic reproductive process of female mammals and is essential for fertilization and embryo development. Recent studies have shown that epigenetic modifications play an important role in the regulation of mammalian reproductive processes (such as oogenesis, spermatogenesis, preimplantation embryo development and sex differentiation). Taking histone acetylation as an instance, the dynamic changes of histone acetyltransferases (HATs) and deacetylases (HDACs) are involved in the regulation of gene activation and inactivation when numerous key physiological events occur during reproduction. Thereinto, HDAC1 and HDAC2, which are highly homologous in terms of both structure and function, play a pivotal role in murine oogenesis. HDAC1 and 2 jointly regulate the global transcription and the incidence of apoptosis of growing oocytes and affect its subsequent growth and development, which reflects their compensatory function. In addition, HDAC1 and 2 also play a specific part in oogenesis respectively. It has shown that HDAC2 is more critical than HDAC1 for oocyte development, which regulates de novo DNA methylation and chromosome segregation. Reciprocally, HDAC1 is more critical than HDAC2 for preimplantation development. Deficiency of HDAC1 causes the decreased proliferation of embryonic stem cells and the smaller embryoid bodies with irregular shape. In this review, we summarized the role and the current research progress of HDAC1/2 in murine oogenesis, to provide a reference for further understanding the relationship between epigenetic modifications and reproductive regulation.
Acetylation ; Animals ; Embryonic Development ; Female ; Histone Deacetylase 1/metabolism* ; Histone Deacetylase 2/metabolism* ; Histone Deacetylases/metabolism* ; Male ; Mice ; Oocytes ; Oogenesis

In recent years,microRNAs(miRNAs)have been detected at different stages of follicular development and in different cells of follicles.Extracellular vesicle(EV)-derived miRNAs have also been detected in the follicular fluid of mature follicles.miRNAs participate in the regulation of normal follicular development,and the regulation disorder may lead to the occurrence of some ovarian diseases.In order to further systematically elucidate the regulatory mechanism of miRNAs on follicular development and find suitable EV-derived miRNAs that can predict oocyte development,we reviewed the functions of miRNAs in follicular development from the perspectives of granulosa cell development,oocyte development,and hormone synthesis.
Female ; Follicular Fluid ; Granulosa Cells ; Humans ; MicroRNAs/genetics* ; Oogenesis ; Ovarian Follicle

Extracellular vesicles (EVs) refer to bilayer membrane transport vesicles secreted by cells. EVs can take macromolecules from cells and transfer them to receptor cells. Among these macromolecular substances, the most studied are microRNAs (miRNAs). miRNA is non-coding RNA involved in the regulation of gene expression. It has been confirmed that there are different non-coding RNAs in mammalian follicular fluid EVs. EVs carrying miRNA can act as an alternative mechanism for autocrine and paracrine, affecting follicular development. This paper systematically introduced the kinds, characteristics and methods of isolation and identification of EVs, focusing on the effects of EVs and miRNAs on follicular development, including early follicular development, oocyte maturation, follicular dominance and effects on granulosa cell function. At the same time, the authors prospected the future research of EVs and microRNAs in follicular fluid, and provided ideas and directions for the research and application of EVs and miRNA functions in follicular fluid.
Animals ; Extracellular Vesicles ; metabolism ; Female ; Follicular Fluid ; chemistry ; Granulosa Cells ; drug effects ; MicroRNAs ; pharmacology ; Oogenesis ; drug effects

PURPOSE: The aim of this study was to investigate how type I diabetes mellitus (T1D) affects the folliculogenesis and oocyte development, fertilization, and embryo development. MATERIALS AND METHODS: A comparative animal study was conducted using two different mouse models of T1D, a genetic AKITA model and a streptozotocin-induced diabetes model. Ovarian function was assessed by gross observation, immunoblot, immunohistochemistry, oocyte counting, and ELISA for serum hormones (insulin, anti-Mullerian hormone, estradiol, testosterone, and progesterone). Maturation and developmental competence of metaphase II oocytes from control and T1D animals was evaluated by immunofluorescent and immunohistochemical detection of biomarkers and in vitro fertilization. RESULTS: Animals from both T1D models showed increased blood glucose levels, while only streptozotocin (STZ)-injected mice showed reduced body weight. Folliculogenesis, oogenesis, and preimplantation embryogenesis were impaired in both T1D mouse models. Interestingly, exogenous streptozotocin injection to induce T1D led to marked decreases in ovary size, expression of luteinizing hormone/chorionic gonadotropin receptor in the ovaries, the number of corpora lutea per ovary, oocyte maturation, and serum progesterone levels. Both T1D models exhibited significantly reduced pre-implantation embryo quality compared with controls. There was no significant difference in embryo quality between STZ-injected and AKITA diabetic mice. CONCLUSION: These results suggest that T1D affects folliculogenesis, oogenesis, and embryo development in mice. However, the physiological mechanisms underlying the observed reproductive effects of diabetes need to be further investigated.
Animals ; Anti-Mullerian Hormone ; Biomarkers ; Blood Glucose ; Body Weight ; Corpus Luteum ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Embryonic Development ; Embryonic Structures ; Enzyme-Linked Immunosorbent Assay ; Estradiol ; Female ; Female ; Fertility ; Fertilization ; Fertilization in Vitro ; Gonadotropins ; Humans ; Immunohistochemistry ; Lutein ; Mental Competency ; Metaphase ; Mice ; Oocytes ; Oogenesis ; Ovary ; Pregnancy ; Progesterone ; Reproduction ; Streptozocin ; Testosterone

Reproduction, fat metabolism, and longevity are intertwined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modulating fat metabolism and lifespan are poorly understood. Here, we find that an oogenesis-enriched gene, c30f12.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Meanwhile, c30f12.4 mutant worms display a shortened lifespan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.
Animals ; Caenorhabditis elegans ; genetics ; metabolism ; Caenorhabditis elegans Proteins ; genetics ; metabolism ; Female ; Lipid Droplets ; metabolism ; Lipid Metabolism ; physiology ; Longevity ; physiology ; Mutation ; Oogenesis ; physiology

One of the key factors of early development is the specification of competence between the oocyte and the sperm, which occurs during gametogenesis. However, the starting point, growth, and maturation for acquiring competence during spermatogenesis and oogenesis in mammals are very different. Spermatogenesis includes spermiogenesis, but such a metamorphosis is not observed during oogenesis. Glycosylation, a ubiquitous modification, is a preliminary requisite for distribution of the structural and functional components of spermatids for metamorphosis. In addition, glycosylation using epididymal or female genital secretory glycans is an important process for the sperm maturation, the acquisition of the potential for fertilization, and the acceleration of early embryo development. However, nonemzymatic unexpected covalent bonding of a carbohydrate and malglycosylation can result in falling fertility rates as shown in the diabetic male. So far, glycosylation during spermatogenesis and the dynamics of the plasma membrane in the process of capacitation and fertilization have been evaluated, and a powerful role of glycosylation in spermatogenesis and early development is also suggested by structural bioinformatics, functional genomics, and functional proteomics. Further understanding of glycosylation is needed to provide a better understanding of fertilization and embryo development and for the development of new diagnostic and therapeutic tools for infertility.
Acceleration ; Birth Rate ; Cell Membrane ; Computational Biology ; Embryonic Development ; Female ; Fertilization ; Gametogenesis ; Genomics ; Glycosylation* ; Humans ; Infertility ; Male ; Mammals ; Mental Competency ; Oocytes ; Oogenesis ; Polysaccharides ; Pregnancy ; Proteomics ; Sperm Maturation ; Spermatids ; Spermatogenesis ; Spermatozoa*

The development of female germ cell is the cornerstone for animal reproduction. Mammalian oocyte and early embryo have many distinct phenomena and mechanisms during their growth and development, involving series dynamic changes of protein synthesis/degradation and phosphorylation. Research on the regulatory mechanism of oocyte division, maturation, and developmental principle of pre-implantation embryo is an important topic in the field of animal developmental biology. Proteomics using all of proteins expressed by a cell or tissue as research object, systematically identify, quantify and study the function of all these proteins. With the rapid development of protein separation and identification technology, proteomics provide some new methods and the research contents on fields of oogenesis, differentiation, maturation and quality control, such as protein quantification, modification, location and interaction important information which other omics technology can not provide. These information will contribute to uncover the molecular mechanisms of mammalian oocyte maturation and embryonic development. And it is great significant for improving the culture system of oocyte in vitro maturation, the efficiency of embryo production in vitro, somatic cell clone and transgenic animal production.
Animals ; Cells, Cultured ; Embryonic Development ; Female ; Humans ; Mammals ; growth & development ; Oocytes ; metabolism ; Oogenesis ; Pregnancy ; Proteomics