Ovaries | You and Your Hormones from the Society for Endocrinology
Because the entire stock of oocytes in primordial follicles is in meiotic prophase, Relation between granulosa number in the largest cross section of the follicle .. in polycystic ovaries: A proposed mechanism for the genesis of cystic follicles. Feb 27, The difference is that a follicle has a microscopic oocyte (egg) maturing inside of it, a simple cyst does not. Because they look the same on. The ovaries release an egg (oocyte) at the midway point of each menstrual cycle. Usually These follicles appear as cysts in the ovaries on an ultrasound scan.
The amount of time that oogonia multiply by mitosis is not species specific. In the human fetus, cells undergoing mitosis are seen until the second and third trimester of pregnancy. Therefore, the total number of gametes is established at this time. For several primary oocytes that complete meiosis I each month, only one or a few functional oocyte, the dominant follicles, completes maturation and undergoes ovulation.
The other follicles that begin to mature will regress and become atretic follicles, eventually deteriorating. The primary oocyte turns into a secondary oocyte in mature ovarian follicles.
Unlike the sperm, the egg is arrested in the secondary stage of meiosis until fertilization. Upon fertilization by sperm, the secondary oocyte continues the second part of meiosis and becomes a zygote. The mitochondria appear aggregated at one pole of the oocyte nucleus i.
A total of 19 cuboidal granulosa cells are seen, one of which is giving rise to a second layer of cells. Diagram of the proposed mechanism for the autocrine control of follicle-stimulating hormone receptor expression in granulosa cells of preantral follicles. Dissociation of endocrine and gametogenic ovarian function. In Lobo R ed: Beginning approximately at the time of recruitment, the oocyte begins to grow and differentiate.
This period is marked by a progressive increase in the level of oocyte RNA synthesis. For example, the genes encoding the zona pellucida ZP proteins i. The importance of the zona pellucida is emphasized by the fact that the carbohydrate moiety of ZP-3 is the species-specific sperm-binding molecule.
Gap junctions are intercellular channels composed of proteins called connexins. This communication between the granulosa and oocyte remains throughout folliculogenesis and is responsible for the synchronous expression of important activities positive and negative.
Electron micrograph of the oocyte-corona radiata granulosa cells in a preantral follicle. The granulosa cell processes traversing the zona pellucida ZP make small gap junctions arrowheads with the oocyte plasma membrane.
Ovarian follicle - Wikipedia
Larger gap junctions arrows are evident between corona radiata cells. Cell-to-cell communication and ovulation: A study of the cumulus-oocyte complex. J Cell Biol A secondary follicle is a preantral follicle with 2 to 10 layers of cuboidal or low columnar cells that form a stratified epithelium Fig.
As seen in Figure 10, the transition from a primary to a secondary follicle involves the acquisition of a second layer of granulosa cells. This transition is accomplished by the continuing division of the granulosa cells. The mechanisms regulating granulosa mitosis are poorly understood. However, exciting research in rodents has provided compelling evidence for the involvement of an oocytederived growth factor, called growth differentiation factor-9 GDF A fundamental concept that emerges from this work is that the oocyte plays a pivotal role in regulating folliculogenesis through its ability to produce novel regulatory ligands e.
GDF-9which are crucial for folliculogenesis. A typical healthy secondary follicle contains a fully grown oocyte surrounded by the zona pellucida, five to eight layers of granulosa cells, a basal lamina, and developing theca tissue with numerous blood vessels. WB Saunders,with permission from Arnold Ltd.
One of the most important changes that occur in the development of a secondary follicle is the acquisition of a theca layer. This tissue, which consists of a layer of stroma-like cells around the basal lamina, subsequently differentiates into the inner theca interna and outer theca externa Fig.
Theca development is accompanied by the neoformation of numerous small vessels, presumably through angiogenesis Fig. This is a critical event because blood circulates around the follicle, bringing nutrients and hormones e.
FSH, LH to and waste and secretory products from the secondary follicle. In this regard, some stromal cells in the inner layer express LH receptors.
The outer layer of stroma cells subsequently differentiates into smooth muscle cells called the theca externa. These smooth muscle cells are innervated by the autonomic nervous system.
It is well documented in rodents that granulosa cells play an obligatory role in the growth and differentiation of the oocyte. The underlying mechanism for the inhibition remains unknown; however, there is evidence to support the concept that granulosa derived cAMP may play an important role in inhibiting the resumption of meiosis.
Diagram showing the relation between the size of the oocyte and the size of the follicles in the human infant ovary. The growth of the oocyte and follicle in the adult rat. Follicle-stimulating hormone FSH receptor signal transduction in the granulosa cells leads to increased cAMP production.
When a preantral follicle completes the secondary stage in development, it contains five distinct structural units: The first indication of the onset of tertiary follicle development is the appearance of a cavity in the granulosa cells. This process, called cavitation or beginning antrum formation, is characterized by the accumulation of fluid between the granulosa cells that in time results in the formation of an internal cavity Fig.
At completion of cavitation, the basic plan of the graafian follicle is established, and all the various cell types are in their proper position awaiting the stimuli that will shift them along paths of differentiation and proliferation Fig. Based on evidence from polyoocyte follicles, the specification mechanism of cavitation probably is tightly regulated Fig. Photomicrograph of an early tertiary follicle 0.
Photomicrograph of a polyovular follicle at the early tertiary stage shows the sites of cavitation or early antrum formation clear spaces just above oocytes asterisk. This event, which is under intraovarian control, seems to arise in a specific synchronized manner and establishes the polarity of the follicle.
Comparative studies on the ultra-structure of mammalian oocytes. University Park Press, What controls cavitation or early antrum formation? It is well known that cavitation occurs in hypophysectomized animals, demonstrating that pituitary hormones such as FSH are not required for this morphogenetic event. Two growth factors expressed in the follicle itself have been implicated in cavitation: Treating cultured granulosa cells with activin causes morphogenetic changes that result in the formation of a histologic unit with an antrum-like cavity.
A graafian follicle can be defined structurally as a heterogeneous family of relatively large follicles 0. The characteristic structural unit of all graafian follicle is the antrum.
For this reason, the term antral follicle is used correctly as a synonym for graafian follicle. The follicular fluid is the medium in which the granulosa cells and oocyte are found and through which regulatory molecules must pass on their way to and from this microenvironment. It is clear that follicle development and ovulation occur in birds and amphibians despite the absence of an antrum and follicular fluid.
Nonetheless, its presence in all mammalian species testifies to its physiologic importance. A graafian follicle is a three-dimensional structure with a central antrum surrounded by a variety of different cell types Fig. There are six distinct histologic components in the graafian follicle, including the theca externa, theca interna, basal lamina, granulosa cells, oocyte, and follicular fluid Fig. A graafian follicle does not change its morphologic complexity as growth proceeds.
All graafian follicles have this same basic architecture; even though there are dramatic changes in graafian follicle size, their appearance remains more or less the same. Diagram of the architecture of a typical class 5 graafian follicle. The theca externa Fig. The corpus luteum retains a theca externa throughout its life, 42 but the significance during luteinization and luteolysis is not known. Drawing of the wall of a graafian follicle. The theca interna is composed of differentiated TICs located within a matrix of loose connective tissue and blood vessels Fig.
In all graafian follicle, LH is a key regulatory hormone for TIC function, and its importance in regulating TIC androgen production in vivo and in vitro has been established. FSH, LHnutrient molecules, vitamins, and cofactors required for the growth and differentiation of the oocyte and granulosa cells. We know little about the regulatory elements that control the theca vasculature. A functional link between the vasculature and graafian follicle development is suggested by the evidence 43 that all monkey graafian follicles express high levels of FSH and LH receptor regardless of size, but when I-human chorionic gonadotropin hCG is injected systemically, only the dominant graafian follicle appears capable of accumulating I-hCG in the theca interna.
These results suggest that the dominant graafian follicle expresses increased vascularization, which plays an important role in its selected maturation. In this regard, follicle-derived vascular endothelial growth factor 4445 and other angiogenic factors such as endothelin 46 are being intensively investigated. The theca compartments i. In a broad sense, there is little or no evidence that major changes occur in the theca layers during the various stages of graafian follicle development beyond those related to vascular and proliferative activities.
This could imply that it is the granulosa cells and perhaps the oocyte that are variable and therefore responsible for graafian follicle diversity. In the graafian follicle, the granulosa cells and oocyte exist as a mass of precisely shaped and precisely positioned cells Fig. The spatial variation creates at least four different granulosa cell layers or domains: A characteristic histologic property of the membrana domain is that it is composed of a pseudostratified epithelium of tall columnar granulosa cells, all of which are anchored to the basal lamina.
Diagram of the structure and function heterogeneity of the granulosa cells in a healthy graafian follicle. The relative position of a granulosa cell in the cellular mass determines its proliferation and differentiation potential.
In Adashi EY ed: Evolving Scientific and Clinical Concepts. The differentiation of a granulosa cell can be traced to its position within the cellular mass Fig.
For example, cells in the membrana domain stop proliferating before those in central domain. The cessation of mitosis in the membrana domain is characterized by the progressive expression of overt differentiation in which they assume the functional phenotype of fully differentiated cells.
This process requires the temporal and coordinate expression of genes that form the basis of granulosa cytodifferentiation. The mechanisms by which this occurs involves ligand-dependent signaling pathways that are coupled to the activation and inhibition of specific genes.
For example, normal differentiation of the membrana granulosa cells requires the activation of specific genes, including those for cytochrome P aromatase Parom 49 and the LH receptor, 50 and the inhibition of structural genes in the apoptotic pathway.
In contrast, the granulosa cells in the periantral, cumulus, and corona radiata domains proliferate, but they fail to express the genes that are involved in a terminal differentiation Fig. What controls granulosa heterogeneity? All the granulosa cells in the healthy graafian follicle express FSH receptor, 135152 and it has been shown that murine granulosa cells in the membrana and cumulus domains produce cAMP in response to FSH stimulation.
The idea that the oocyte plays a key role in causing the different patterns of granulosa cytodifferentiation during graafian follicle development is supported by studies in rodents.
In developing murine graafian follicles, the differential pattern of proliferation and differentiation between the granulosa in the membrana and cumulus domains are under the control of secreted oocyte morphogens.
These data support the idea that GDF-9 secreted by the egg is obligatory for graafian follicle development, granulosa cytodifferentiation and proliferation, and female fertility. The concept that oocyte-derived growth factors control folliculogenesis and fertility could have important implications for human physiology and pathophysiology.
All graafian follicles can be divided broadly into two groups: The main difference between these two groups is whether apoptosis is occurring in the granulosa cells. The development of a graafian follicle healthy or atretic follows a progressive course over time. This implies that variability or heterogeneity is a normal consequence of folliculogenesis.
A healthy graafian follicle becomes progressively more differentiated with increasing time until it attains the preovulatory stage Fig.
The time for this process Fig. In healthy follicles, these genes direct cytodifferentiation, proliferation, and follicular fluid formation. In atretic follicles, the time-dependent changes in gene expression cause the cessation of mitosis and the expression of apoptosis i. During atresia, the oocyte and granulosa cells become committed to express genes that lead to apoptosis. Understanding the molecular mechanisms and cellular consequences of the ligand-receptor signaling pathways that control graafian follicle fate is a major goal of reproductive research.
The two major classes of graafian follicles: Each undergoes a regulated course of progressive change that results in ovulation or apoptosis. Diagram of the life cycle of graafian follicles in human ovaries. The process of graafian follicle growth and development can be arbitrarily divided into several stages based on follicle size Figs. It is convenient and important for clinicians and researchers to identify the physiologic function of various types or classes of follicles over the cycle.
The healthy human graafian follicle has a destiny to complete the transition from the small 1 to 6 mmmedium 7 to 11 mmand large 12 to 17 mm to the fully differentiated preovulatory state 18 to 23 mm.
The atretic graafian follicle has a destiny to complete the transition from the small to the medium stage 1 to 10 mm but appears incapable of growing to the large size under normal physiologic conditions. Each of these morphologically distinct graafian follicles is a dynamic structure undergoing a flow or progression of developmental change on its way to becoming more differentiated or more atretic Fig. It should be kept in mind that this results in the presence of an extremely heterogeneous pool of graafian follicles.
It is the heterogeneity that makes it difficult to come to grips with a simple functional definition for the graafian follicle. The size of a graafian follicle is determined largely by the size of the antrum, which is determined by the volume of follicular fluid, which is determined by the bioavailability of FSH in the fluid.
In the absence of FSH, follicular fluid is not produced, and no graafian follicles develop. The proliferation of the follicle cells also contributes to graafian follicle growth; in healthy follicles, the granulosa and theca cells proliferate extensively as much as foldconcomitant with the antrum becoming filled with follicular fluid Fig.
Changes in the number of granulosa cells and volume of follicular fluid in human graafian follicles throughout the course of folliculogenesis.
The dominant follicle at ovulation is about 25 mm in diameter and contains about 50 million granulosa cells and 7 ml of follicular fluid. Hormonal correlates of follicular development in the human ovary. Aust J Biol Sci Selection of the Dominant Follicle. After puberty, hormones cause the maturation of follicles along with the primary oocytes. The maturation of both follicle along with the ovum causes the ovulation where the mature ovum is released from the ovary.
Human Graafian follicle is shown in figure 2. The oocyte is the large, pink color cell at the top of the follicle. Graafian Follicle The developmental process of the follicle is referred to as folliculogenesis. Primordial resting follicle, primary folliclesecondary pre-antral follicle, tertiary antral follicle and pre-ovulatory Graafian follicle are the stages of folliculogenesis.
The primordial follicle is arrested at the diplotene stage of meiosis 1. It contains a single layer of squamous, granulosa cell layer.
The conversion of the squamous, granulosa cells into cuboidal, granulosa cells is called the initial recruitment of the folliculogenesis. At the stage of single layer of cuboidal, granulosa cell layer, the follicle is called the primary follicle. In the primordial follicle, zona pellucida is developed, surrounding the oocyte. The secondary follicle contains 2 to 10 layers of granulosa cells. In the tertiary follicle, a cavity appears inside the granulosa cell layer.
The Graafian follicle is relatively a large follicle. The cavity of the granulosa cell layer contains follicular fluid. The rupture of the Graafian follicle causes ovulation. Similarities Between Oocyte and Follicle Both oocyte and follicle are two developing structures found inside the ovary. The development of both oocyte and follicle occur in the ovary cortex.