The source of the female gamete, the oocyte, egg or ovum is the ovary and its release is called ovulation. This page gives an overview of the ovary structure, follicle and oocyte development.
Ovulation (Play ovulation movie in new window, rabbit ovary modified from "In the Beginning" 1935)
The 2 human ovaries gradually lose follicles both before and after puberty (the beginning of ovulation); beginning with about 7 million before birth, 2 million at birth, 300-400,000 by puberty and finally by late 40’s have only a few follicles left (More? Oogenesis). The number of antral follicles detected within the ovary also decreases with increasing materal age. In humans, a primodial follicle take about 150 days to develop into a preantral follicle (primary) and another 120 days to form an antral follicle (secondary). A number of antral follicles will then "compete" for 14-15 days to become the dominant follicle, which will undergo ovulation.
Mature Human Egg: large egg in comparison to surrounding granulosa cells.
This current page also has histological images of an ovary (based upon UNSW Slide 92) showing follicles at various states of development. There is also a variety (as usual) of nomenclature used for different stages in the maturation of the follicle.
Page Links: Introduction | Some Recent Findings | Oogenesis | Postnatal Oogenesis | | Hypothalamus Pituitary Gonad Axis | Ovary Histology | Ovary Cortex | Primordial Follicles | Preantral Follicle | Antral Follicle | Follicle Classification | Follicle Structure | Early Follicle Development | Ovulation | Follicle Post-Ovulation | Uterine Tube | Ovarian Angiogenesis | Histology- Female Genital System | References | Glossary | Terms
Related Pages: Corpus Luteum | Human Menstrual Cycle | Developing Ovary | Development of the Reproductive System
Yoshino O, McMahon HE, Sharma S, Shimasaki S. A unique preovulatory expression pattern plays a key role in the physiological functions of BMP-15 in the mouse. Proc Natl Acad Sci U S A. 2006 Jul 3
"Bone morphogenetic protein 15 (BMP-15) gene cause female infertility in the monoovulatory human and sheep; however, in the polyovulatory mouse, loss-of-function of BMP-15 results only in reduced ovulation rate. ...The species-specific differences in the phenotypes caused by BMP-15 mutations may thus be attributed to the temporal variations in the production of the mature form of BMP-15."
Yoon SJ, Kim KH, Chung HM, Choi DH, Lee WS, Cha KY, Lee KA. Gene expression profiling of early follicular development in primordial, primary, and secondary follicles. Fertil Steril. 2006 Jan;85(1):193-203. (mouse)
"....analyzed a list of genes according to function, such as apoptosis, cell cycle, cell proliferation and maintenance, cytoskeleton, extracellular matrix, and signal transduction, as well as according to frequency. Among the list of genes, we found all PDGFs (A, B, C, and D) and receptors (alpha and beta) are expressed with differential expression patterns in the oocytes and ovarian cells according to stage of follicular development."
Pangas SA, Rajkovic A. Transcriptional regulation of early oogenesis: in search of masters. Hum Reprod Update. 2006 Jan-Feb;12(1):65-76.
"Transcription factors in the germline play important roles in ovary formation and folliculogenesis, and control both oocyte development and somatic cell function. Factor in the germline (Figla) and newborn ovary homeobox gene (Nobox) represent a growing number of oocyte-specific transcription factors that regulate genes unique to oocytes."
Eggs in the developing human ovary the number of oogonia/ovary increased from 26,000 (week 6) to 250,000 (week 9). Bendsen E, Byskov AG, Andersen CY, Westergaard LG. Number of germ cells and somatic cells in human fetal ovaries during the first weeks after sex differentiation. Hum Reprod. 2006 Jan;21(1):30-35.
The graph below shows the changes in human germ cell numbers in the ovary with age, peaking at about 7 million (occuring in early fetal development) and then decreasing by apotpotic cell death. At puberty there remain only about 400,000 and only about 10% of these will be released through reproductive life.
(Based on data from: Hassold, etal., Environ Mol Mutagen 1996. 28: 167-175)
There is a dogma in mammalian development that new oocyte and follicle production does not occur during postnatal life. There is substantial data that shows human ovarian changes postnatally are loss by apoptosis of prenatal oocytes.
A research group (Tilly JL, Johnson J. 2004, 2007) has recently published experiments using mice, showing potentially other sources/sites (bone marrow) of oocyte (putative germ cell) generation. They recently stated that the argument should be based upon "experimental approaches than simply an absence of evidence, especially from gene expression analyses". Several other research groups (Eggan K etal. 2004 and Veitia etal. 2007) have argued against these findings.
Thus the possibility/potential for mammalian postnatal oogenesis to occur is still contentious with limited research findings to currently support this concept.
References:
The diagram shows the hormonal regulation pathway from the brain to the ovary and subsequent impact on uterine changes during the menstral cycle. LHRH = Luteinizing Hormone-Releasing Hormone, also called gonadotropin-releasing hormone (GnRH). This peptide hormone is a decapeptide (10 amino acids) with a short half life (<15 minutes). LH = Luteinizing Hormone FSH = Follicle Stimulating Hormone
A similar endocrine axis is also found for regulation of the male gonad. |
(Image: NIAAA Emanuele, M.A. etal) |
This histological section is of an entire ovary (cat) showing the gross organization into a cortical region containing early follicles and a medullary region which contains many large maternal blood vessels.
Features:
Low power view of ovary cortex and some medullary region. Note that in many follicles the oocyte is not visible due to its relatively small size and the position of the plane of section through the follicle.
Features:
View of cortical ovary region showing primordial follicles and a single preantral follicle, with atretic follicle to its left. Note the arrangement, number and size of the primordial follicles compared with the next stage of development, the preantral follicle.
At the bottom of the left image is a single preantral (primary) follicle. The oocyte has increased substantially in cytoplasmic and nuclear size. Surrounding the oocyte is the specialized extracellular matrix, the zona pellucida (pink layer). Surrounding the zona pellucida is a single layer of granulosa cells, note the possible single Call-Exner body (a spherical eosinophilic region) within the granulosa layer. Surrounding the granulosa cells are the developing thecal layers (flattened cells), note also the vascularization of this layer by small capillaries (red).
The image on the right shows a preantral follicle now with two layers of granulosa cells.
The image on the left also shows other cortical features: germinal epithelium, tunica albuginea, primordial follicles and ovarian stroma.
View of the ovary cortex and medullary region showing large-preovulatory follicle and early stages of follicle development. The right hand image shows the attachment of the oocyte to the follicle wall by the cumulus oophorus.
In Humans
There are several different nomenclatures for the stages of follicle maturation.
Atresia
At any one time the majority of follicles are destined not to complete maturation and at any stage (from type 4-7) degeneration of the follicle can occur. This process is called ATRESIA.
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Granulosa Cells
A specific cell type that proliferates in association with the oocyte within the developing follicles of the ovary. These cells form the follicle stratum granulosa and are also given specific names based upon their position within the follicle.
(Greek, thek = box) The ovarian follicle endocrine cells forming the inner layer of the theca folliculi surrounding the developing follicle within the ovary. This vascularized layer of cells respond to leutenizing hormone (LH) synthesizing and secreting androgens (androstendione) transported to glomerulosa cells which process initially into testosterone and then by aromatase into estrogen (estradiol). Theca cells do not begin hormonal functions until puberty.
The ovarian follicle stromal cells forming the outer layer of the theca folliculi surrounding the developing follicle within the ovary. Consisting of connective tissue cells, smooth muscle and collagen fibers.
Ovulation results in release of the oocyte with granulosa supporting cells and follicular fluid into the peritoneal cavity. The uterine tube which is nearby and sits anatomically over the ovary is the destination of the egg, but it may also be lost into the peritonaly cavity.
The uterine tube or Fallopian tube or oviduct is closely associated with but no connection with the ovary and has been described in 4 anatomical regions.
There are recent studies into several factors (KGF, LIF, BMP4) involved in the development of the early follicle development, from primordial to primary follicle.
Kezele P, Nilsson EE, Skinner MK. Keratinocyte growth factor acts as a mesenchymal factor that promotes ovarian primordial to primary follicle transition. Biol Reprod. 2005 Nov;73(5):967-73.
Nilsson EE, Kezele P, Skinner MK. Leukemia inhibitory factor (LIF) promotes the primordial to primary follicle transition in rat ovaries. Mol Cell Endocrinol. 2002 Feb 25;188(1-2):65-73.
Nilsson EE, Skinner MK. Bone morphogenetic protein-4 acts as an ovarian follicle survival factor and promotes primordial follicle development. Biol Reprod. 2003 Oct;69(4):1265-72
Ovulation can be determined by a number of different luteinizing hormone (LH) urinary tests.
Commercial tests: OvuQuick, Clearplan, OvuKit, Sure Step, Q Test Ovulation Predictor, and EZ LH (Note: commercial information is listed only for educational information purposes and is not an endorsement)
Reference:
Nielsen MS, Barton SD, Hatasaka HH, Stanford JB. Comparison of several one-step home urinary luteinizing hormone detection test kits to OvuQuick. Fertil Steril. 2001 Aug;76(2):384-7.
Miller PB, Soules MR. The usefulness of a urinary LH kit for ovulation prediction during menstrual cycles of normal women. Obstet Gynecol. 1996 Jan;87(1):13-7.
Matijevic R, Grgic O. Predictive values of ultrasound monitoring of the menstrual cycle. Curr Opin Obstet Gynecol. 2005 Aug;17(4):405-10.
Following ovulation the remains of the ovulating follicle within the ovary has two distinct futures, depending on whether fertilization and implantation has occurred over the next two weeks.
No Implantation
If no implantation has occurred, then the follicle forms a structure that will degenerate the corpus albicans.
Implantation
If implantation has occurred, then the follicle is stimulated by the hormone hCG released from the conceptus that reaches the ovary through the maternal blood stream. This hormone leads to the follicle forming the corpus luteum, which now acts as an endocrine organ secreting high levels progesterone. This progesterone now maintains the uterine endometrium and prevents its normal loss and menstruation.
(More? corpus luteum | Week 2 - Ovary)
(from: Advances in Ultrasound Assessment in the Establishment and Development of Pregnancy. Sladkevicius P & Campbell S. British Medical Bulletin 2000; 56: 691-703)
Virtual Slidebox of Histology Female genital tract
Blue Histology Female Reproductive System
Links: Journals | Online Textbooks | Search Textbooks | PubMed | Search PubMed | Glossary
Molecular Biology of the Cell (4th Edn) Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter. New York: Garland Publishing; 2002. Image: The stages of oogenesis | Eggs Develop in Stages |
Developmental Biology (6th Edn) Gilbert, Scott F. Sunderland (MA): Sinauer Associates, Inc.; c2000. oogenesis | Image: The ovarian follicle of mammals
Search NLM Online Textbooks- "oogenesis" : Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach
Reviews
Articles
Search PubMed
Search April 2006 "oogenesis" 2123 reference articles of which 272 were reviews.
Search PubMed: term = oogenesis | term = ovary follicle development | term = follicle atresia
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antrum (Latin from Greek, antron = a cave, cavity; a nearly-closed cavity or bulge), in the ovary this refers to the follicular fluid-filled space within the late follicle (antral follicle). The absence (preaantral) or presence of an antrum is used to define the maturation of a follicle (absence = early, presence=late).
Call-Exner bodies - A feature seen in the developing ovarian follicle granulosa layer of some species, including human. Appears as a spherical space staining as an eosinophilic region and contains basal lamina components (type IV collagen and laminin) similar to thiose of the follicular basal lamina.
corpus luteum (Latin, corpus = body, luteum = yellow) The remains of ovarian follicle after ovulation that acts as an endocrine organ (produce progesterone and oestrogens) supporting pregnancy and preventing menstruation (loss of the endometrial lining). Formed by proliferation of both follicular granulosa cells (granulosa lutein cells) and thecal cells (theca lutein cells) after ovulation. granulosa lutein cells and theca lutein cells and produce progesterone and oestrogens. de Graaf first observed it in the ovary of a cow as a yellow structure. (More? corpus luteum)
dominant antral follicle See also non-dominant antral follicle.
follicle atresia degeneration of the follicle, which can occur at any stage of follicular development.
follicle (Latin, folliculus = little bag, dim. of Latin follis) the functional unit within the ovary that includes the developing oocyte (egg) and the surrounding layers of cells that support that oocyte.
follicular basal lamina - The basal lamina beneath the membrana granulosa (granulosa cell) layer of the developing follicles of the ovary. It separates the stratum granulosa from the thecal layers. Thought to be synthesized by granulosa cells, but may also have a contribution from the thecal layer.
follicular fluid the fluid found in the antrum of the antral follicle (secondary follicle). This fluid is secreted by glomerulosa cells in the wall of the follicle, accumulates around the developing egg, and is the fluid carrier of the released oocyte at ovulation.
granulosa cell - A specific cell type that proliferates in association with the oocyte within the developing follicles of the ovary. These cells form the follicle stratum granulosa and are also given specific names based upon their position within the follicle. In the antral follicle, membrana granulosa sits on the follicular basal lamina and lines the antrum as a stratified epitelium. The cumulus oophorus is a column of granulosa cells that attaches the oocyte to the follicle wall. The corona radiata are the granulosa cells that directly surround the oocyte, and are released along with it at ovulation. Following ovulation the corona radiata provide physical protection to the oocyte and granulosa cells within the ovulating follicle contribute to corpus luteum.
theca externa - The ovarian follicle stromal cells forming the outer layer of the theca folliculi surrounding the developing follicle within the ovary. Consisting of connective tissue cells, smooth muscle and collagen fibers.
theca interna - The ovarian follicle stromal cells forming the inner layer of the theca folliculi surrounding the developing follicle within the ovary. This vascularized layer of cells respond to leutenizing hormone (LH) synthesizing and secreting androgens which are processed into estrogen. Theca cells do not begin secreting estrogen until puberty.
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This page is an overview of the ovary and the development of egg (oogenesis) and the surrounding follicle and should be read along with those on the Human Menstrual Cycle.
The surrounding follicular cells have an important role in hormone synthesis and release into local circulation (shown in the ovary medulla) and systemic circulation.
The follicle has an important role in maintaining the early stages of development (preventing menses) (More? Corpus Luteum)
Please email Dr Mark Hill if you wish to make a comment about this current project.
