Growth Differentiation Factor 9: A bone morphogenetic protein that plays an essential role in the regulation of ovarian folliculogenesis.Growth Differentiation Factor 15: A growth differentiation factor that is secreted in response to cell stress and in response to MACROPHAGE ACTIVATION. In addition growth differentiation factor 15 demonstrates a diverse array of biological properties including the induction of cartilage formation, the inhibition of hematopoietic progenitor proliferation, and the induction of neuronal migration.Growth Differentiation Factor 5: A growth differentiation factor that plays a role in early CHONDROGENESIS and joint formation.Growth Differentiation Factors: A family of BONE MORPHOGENETIC PROTEIN-related proteins that are primarily involved in regulation of CELL DIFFERENTIATION.Growth Differentiation Factor 6: A growth differentiation factor that plays a role in the neural differentiation, specifically in the retinal development of the EYE.Growth Differentiation Factor 1: A growth differentiation factor that plays a role in the genesis of left-right asymmetry during vertebrate development. Evidence for this role is seen in MICE where loss of growth differentiation factor 1 function results in right-left isomerism of visceral organs. In HUMANS heterozygous loss of growth differentiation factor 1 function has been associated with CONGENITAL HEART DEFECTS and TRANSPOSITION OF GREAT VESSELS.Bone Morphogenetic Protein 15: A protein that plays a role in GRANULOSA CELLS where it regulates folliculogenesis. Mutations in the gene for bone morphogenetic protein 15 are linked to reproductive abnormalities such as PREMATURE OVARIAN FAILURE.Growth Differentiation Factor 3: A growth differentiation factor that may play a role in maintaining the undifferentiated state of PLURIPOTENT STEM CELLS by inhibiting the actions of BONE MORPHOGENETIC PROTEINS. Differentiation factor 3 is also considered a nodal signaling ligand that influences the genesis of left-right asymmetry.Growth Differentiation Factor 10: A growth differentiation factor that is closely-related in structure to BONE MORPHOGENETIC PROTEIN 3. Growth differentiation factor 10 is found at high levels in BONE, however it plays an additional roles in regulating EMBRYONIC DEVELOPMENT.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Cumulus Cells: The granulosa cells of the cumulus oophorus which surround the OVUM in the GRAAFIAN FOLLICLE. At OVULATION they are extruded with OVUM.Granulosa Cells: Supporting cells for the developing female gamete in the OVARY. They are derived from the coelomic epithelial cells of the gonadal ridge. Granulosa cells form a single layer around the OOCYTE in the primordial ovarian follicle and advance to form a multilayered cumulus oophorus surrounding the OVUM in the Graafian follicle. The major functions of granulosa cells include the production of steroids and LH receptors (RECEPTORS, LH).Myostatin: A growth differentiation factor that is a potent inhibitor of SKELETAL MUSCLE growth. It may play a role in the regulation of MYOGENESIS and in muscle maintenance during adulthood.Ovarian Follicle: An OOCYTE-containing structure in the cortex of the OVARY. The oocyte is enclosed by a layer of GRANULOSA CELLS providing a nourishing microenvironment (FOLLICULAR FLUID). The number and size of follicles vary depending on the age and reproductive state of the female. The growing follicles are divided into five stages: primary, secondary, tertiary, Graafian, and atretic. Follicular growth and steroidogenesis depend on the presence of GONADOTROPINS.Myeloid Differentiation Factor 88: An intracellular signaling adaptor protein that plays a role in TOLL-LIKE RECEPTOR and INTERLEUKIN 1 RECEPTORS signal transduction. It forms a signaling complex with the activated cell surface receptors and members of the IRAK KINASES.Ovary: The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).Smad Proteins: A family of proteins that are involved in the translocation of signals from TGF-BETA RECEPTORS; BONE MORPHOGENETIC PROTEIN RECEPTORS; and other surface receptors to the CELL NUCLEUS. They were originally identified as a class of proteins that are related to the mothers against decapentaplegic protein, Drosophila and sma proteins from CAENORHABDITIS ELEGANS.Follistatin: A broadly distributed protein that binds directly to ACTIVINS. It functions as an activin antagonist, inhibits FOLLICLE STIMULATING HORMONE secretion, regulates CELL DIFFERENTIATION, and plays an important role in embryogenesis. Follistatin is a single glycosylated polypeptide chain of approximately 37-kDa and is not a member of the inhibin family (INHIBINS). Follistatin also binds and neutralizes many members of the TRANSFORMING GROWTH FACTOR BETA family.Gene Expression Regulation, Developmental: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism.Growth Substances: Signal molecules that are involved in the control of cell growth and differentiation.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Hepcidins: Forms of hepcidin, a cationic amphipathic peptide synthesized in the liver as a prepropeptide which is first processed into prohepcidin and then into the biologically active hepcidin forms, including in human the 20-, 22-, and 25-amino acid residue peptide forms. Hepcidin acts as a homeostatic regulators of iron metabolism and also possesses antimicrobial activity.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Neuregulins: A family of peptides originally found as factors that stimulate the phosphorylation of the erbB-2 receptor (RECEPTORS, ERBB-2). Multiple variant forms of NEUREGULINS occur due to alternative splicing of their mRNAs. The NEUREGULINS include products from the three known genes (NGR1; NGR2 and NGR3).Ovulation: The discharge of an OVUM from a rupturing follicle in the OVARY.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Growth Differentiation Factor 2: A growth differentiation factor that plays a regulatory role as a paracrine factor for a diverse array of cell types during EMBRYONIC DEVELOPMENT and in the adult tissues. Growth differentiation factor 2 is also a potent regulator of CHONDROGENESIS and was previously referred to as bone morphogenetic protein 9.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Mice, Inbred C57BLIn Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes.Cell Proliferation: All of the processes involved in increasing CELL NUMBER including CELL DIVISION.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Sheep: Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Kinesis: Locomotor behavior not involving a steering reaction, but in which there may be a turning random in direction. It includes orthokinesis, the rate of movement and klinokinesis, the amount of turning, which are related to the intensity of stimulation.Bone Morphogenetic Protein Receptors, Type I: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Antigens, Differentiation: Antigens expressed primarily on the membranes of living cells during sequential stages of maturation and differentiation. As immunologic markers they have high organ and tissue specificity and are useful as probes in studies of normal cell development as well as neoplastic transformation.Cell Division: The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Stem Cells: Relatively undifferentiated cells that retain the ability to divide and proliferate throughout postnatal life to provide progenitor cells that can differentiate into specialized cells.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Toll-Like Receptor 4: A pattern recognition receptor that interacts with LYMPHOCYTE ANTIGEN 96 and LIPOPOLYSACCHARIDES. It mediates cellular responses to GRAM-NEGATIVE BACTERIA.Paracrine Communication: Cellular signaling in which a factor secreted by a cell affects other cells in the local environment. This term is often used to denote the action of INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS on surrounding cells.Follicle Stimulating Hormone: A major gonadotropin secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Follicle-stimulating hormone stimulates GAMETOGENESIS and the supporting cells such as the ovarian GRANULOSA CELLS, the testicular SERTOLI CELLS, and LEYDIG CELLS. FSH consists of two noncovalently linked subunits, alpha and beta. Within a species, the alpha subunit is common in the three pituitary glycoprotein hormones (TSH, LH, and FSH), but the beta subunit is unique and confers its biological specificity.Follicular Phase: The period of the MENSTRUAL CYCLE representing follicular growth, increase in ovarian estrogen (ESTROGENS) production, and epithelial proliferation of the ENDOMETRIUM. Follicular phase begins with the onset of MENSTRUATION and ends with OVULATION.Activins: Activins are produced in the pituitary, gonads, and other tissues. By acting locally, they stimulate pituitary FSH secretion and have diverse effects on cell differentiation and embryonic development. Activins are glycoproteins that are hetero- or homodimers of INHIBIN-BETA SUBUNITS.Smad3 Protein: A receptor-regulated smad protein that undergoes PHOSPHORYLATION by ACTIVIN RECEPTORS, TYPE I. Activated Smad3 can bind directly to DNA, and it regulates TRANSFORMING GROWTH FACTOR BETA and ACTIVIN signaling.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Receptors, Transforming Growth Factor beta: Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.Gene Expression Profiling: The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.Tissue Culture Techniques: A technique for maintaining or growing TISSUE in vitro, usually by DIFFUSION, perifusion, or PERFUSION. The tissue is cultured directly after removal from the host without being dispersed for cell culture.Tretinoin: An important regulator of GENE EXPRESSION during growth and development, and in NEOPLASMS. Tretinoin, also known as retinoic acid and derived from maternal VITAMIN A, is essential for normal GROWTH; and EMBRYONIC DEVELOPMENT. An excess of tretinoin can be teratogenic. It is used in the treatment of PSORIASIS; ACNE VULGARIS; and several other SKIN DISEASES. It has also been approved for use in promyelocytic leukemia (LEUKEMIA, PROMYELOCYTIC, ACUTE).Cell Lineage: The developmental history of specific differentiated cell types as traced back to the original STEM CELLS in the embryo.Toll-Like Receptors: A family of pattern recognition receptors characterized by an extracellular leucine-rich domain and a cytoplasmic domain that share homology with the INTERLEUKIN 1 RECEPTOR and the DROSOPHILA toll protein. Following pathogen recognition, toll-like receptors recruit and activate a variety of SIGNAL TRANSDUCING ADAPTOR PROTEINS.Toll-Like Receptor 2: A pattern recognition receptor that forms heterodimers with other TOLL-LIKE RECEPTORS. It interacts with multiple ligands including PEPTIDOGLYCAN, bacterial LIPOPROTEINS, lipoarabinomannan, and a variety of PORINS.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Sex Differentiation: The process in developing sex- or gender-specific tissue, organ, or function after SEX DETERMINATION PROCESSES have set the sex of the GONADS. Major areas of sex differentiation occur in the reproductive tract (GENITALIA) and the brain.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Bone Marrow Cells: Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells.Adaptor Proteins, Signal Transducing: A broad category of carrier proteins that play a role in SIGNAL TRANSDUCTION. They generally contain several modular domains, each of which having its own binding activity, and act by forming complexes with other intracellular-signaling molecules. Signal-transducing adaptor proteins lack enzyme activity, however their activity can be modulated by other signal-transducing enzymesRANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Embryonic Stem Cells: Cells derived from the BLASTOCYST INNER CELL MASS which forms before implantation in the uterine wall. They retain the ability to divide, proliferate and provide progenitor cells that can differentiate into specialized cells.Progesterone: The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.B-Lymphocytes: Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation.