Follicular atresia

Follicular atresia is the breakdown of the ovarian follicles, which consist of an oocyte surrounded by granulosa cells and internal and external theca cells. It occurs continually throughout a woman's life, as she is born with millions of follicles but will only ovulate around 400 times in her lifetime.[1][2] Typically around 20 follicles mature each month but only a single follicle is ovulated; the follicle from which the oocyte was released becomes the corpus luteum. The rest undergo follicular atresia.[3][4][5][6]


Atresia is a hormonally controlled apoptotic process[7] that depends dominantly on granulosa cell apoptosis. Follicular atresia is inhibited by follicle-stimulating hormone (FSH), which promotes follicle development.[8] Once the follicle has developed, it secretes estrogen, which in high levels decreases secretions of FSH.[9] Granulosa cell apoptosis is considered the underlying mechanism of follicular atresia, and has been associated with five ligand-receptor systems involved in cell death:[10][11][12][5] They are:

Granulosa cell apoptosis is promoted by tumor necrosis factor-alpha (TNFα), though the mechanism of TNFα is unclear.[13][14]

Fas antigen, a cell surface receptor protein that is expressed on granulosa cells, mediates signals that induce apoptosis by binding Fas ligand and therefore plays an important role in follicular atresia. Lack of a functional Fas ligand / Fas receptor system has been linked to abnormal follicle development, and greater numbers of secondary follicles as a result of the inability to induce apoptosis.[15]

TNF-related apoptosis-inducing ligand TRAIL activates Caspase 3 (CASP3), which in turn interacts with caspases 6, 7, 8, 9, and 10 to induce apoptosis in granulosa cells.[16]

In addition, two intracellular inhibitor proteins, cellular FLICE-like inhibitory protein short form (cFLIPS) and long form (cFLIPL), which were strongly expressed in granulosa cells, may act as anti-apoptotic factors.

It has been proposed that enhanced levels of Nitrogen oxide in rats can prevent atresia of the ovarian follicle, and depressed levels have the opposite effect.[17]

Related diseases

Undergoing follicular atresia is necessary in order for women to maintain a healthy reproductive system. The inability to regulate granulosa cell apoptosis and undergo follicular atresia has been linked to the development of some hormone-related cancers and chemo-resistance.[18]

See also


  1. ^ [Faddy, M. J. "Follicle dynamics during ovarian ageing." Molecular and Cellular Endocrinology 163.1 (2000): 43-48.]
  2. ^ [Hampson, Elizabeth, and Elizabeth A. Young. "Methodological issues in the study of hormone-behavior relations in humans: Understanding and monitoring the menstrual cycle." Sex differences in the brain. From genes to behavior (2008): 63-78.]
  3. ^ Rolaki A, Drakakis P, Millingos S, Loutradis D, Makrigiannakis A (July 2005). "Novel trends in follicular development, atresia and corpus luteum regression: a role for apoptosis". Reprod. Biomed. Online. 11 (1): 93–103. doi:10.1016/S1472-6483(10)61304-1. PMID 16102296.
  4. ^ a b Manabe N, Matsuda-Minehata F, Goto Y, et al. (July 2008). "Role of cell death ligand and receptor system on regulation of follicular atresia in pig ovaries". Reprod. Domest. Anim. 43. Suppl 2: 268–72. doi:10.1111/j.1439-0531.2008.01172.x. PMID 18638134.
  5. ^ a b Manabe N, Goto Y, Matsuda-Minehata F, et al. (October 2004). "Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia". J. Reprod. Dev. 50 (5): 493–514. doi:10.1262/jrd.50.493. PMID 15514456. Archived from the original (– Scholar search) on 2012-12-19.
  6. ^ Hsueh AJ, Billig H, Tsafriri A (December 1994). "Ovarian follicle atresia: a hormonally controlled apoptotic process". Endocr. Rev. 15 (6): 707–24. PMID 7705278.
  7. ^ Kaipia A, Hsueh AJ (1997). "Regulation of ovarian follicle atresia". Annu. Rev. Physiol. 59 (1): 349–63. doi:10.1146/annurev.physiol.59.1.349. PMID 9074768.
  8. ^ [Kaipia, Antti, and Aaron JW Hsueh. "Regulation of ovarian follicle atresia." Annual Review of Physiology 59.1 (1997): 349-363.]
  9. ^ [Marshall, J. C., et al. "Selective inhibition of follicle-stimulating hormone secretion by estradiol. Mechanism for modulation of gonadotropin responses to low dose pulses of gonadotropin-releasing hormone." Journal of Clinical Investigation 71.2 (1983): 248.]
  10. ^ [Manabe, Noboru, et al. "Regulation mechanism of selective atresia in porcine follicles: regulation of granulosa cell apoptosis during atresia." The Journal of reproduction and development 50.5 (2004): 493.]
  11. ^ Matsuda-Minehata F, Goto Y, Inoue N, Manabe N (October 2005). "Changes in expression of anti-apoptotic protein, cFLIP, in granulosa cells during follicular atresia in porcine ovaries". Mol. Reprod. Dev. 72 (2): 145–51. doi:10.1002/mrd.20349. PMID 16010689.
  12. ^ Matsuda F, Inoue N, Goto Y, et al. (October 2008). "cFLIP regulates death receptor-mediated apoptosis in an ovarian granulosa cell line by inhibiting procaspase-8 cleavage". J. Reprod. Dev. 54 (5): 314–20. doi:10.1262/jrd.20051. PMID 18603835. Archived from the original (– Scholar search) on 2012-12-19.
  13. ^ [Sasson, Ravid, et al. "Induction of apoptosis in granulosa cells by TNFα and its attenuation by glucocorticoids involve modulation of Bcl-2." Biochemical and biophysical research communications 294.1 (2002): 51-59.]
  14. ^ [Billig, Hakan, I. T. S. U. K. O. Furuta, and A. J. Hsueh. "Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis." Endocrinology 133.5 (1993): 2204-2212.]
  15. ^ [Sakamaki, Kazuhiro, et al. "Involvement of Fas antigen in ovarian follicular atresia and luteolysis." Molecular reproduction and development 47.1 (1997): 11-18.]
  16. ^ [Inoue, Naoko, et al. "Roles of tumor necrosis factor-related apoptosis-inducing ligand signaling pathway in granulosa cell apoptosis during atresia in pig ovaries." Journal of Reproduction and Development 49.4 (2003): 313-321.]
  17. ^ Najati V, Ilkhanipour M, Salehi S, Sadeghi-Hashjin G (January 2008). "Role of nitric oxide on the generation of atretic follicles in the rat ovaries". Pak. J. Biol. Sci. 11 (2): 250–4. doi:10.3923/pjbs.2008.250.254. PMID 18817198.
  18. ^ [Kim, J. H., et al. "Differential apoptotic activities of wild-type FOXL2 and the adult-type granulosa cell tumor-associated mutant FOXL2 (C134W)." Oncogene 30.14 (2010): 1653-1663.]

N-cadherin, also known as Cadherin-2 (CDH2) or neural cadherin (NCAD) is a protein that in humans is encoded by the CDH2 gene. CDH2 has also been designated as CD325 (cluster of differentiation 325). N-cadherin is a transmembrane protein expressed in multiple tissues and functions to mediate cell–cell adhesion. In cardiac muscle, N-cadherin is an integral component in adherens junctions residing at intercalated discs, which function to mechanically and electrically couple adjacent cardiomyocytes. While mutations in CDH2 have not thus far been associated with human disease, alterations in expression and integrity of N-cadherin protein has been observed in various forms of disease, including human dilated cardiomyopathy.

Corpus luteum

The corpus luteum (Latin for "yellow body"; plural corpora lutea) is a temporary endocrine structure in female ovaries and is involved in the production of relatively high levels of progesterone, moderate levels of estradiol and inhibin A, and small amounts of estrogen. It is the remains of the ovarian follicle that has released a mature ovum during a previous ovulation.The corpus luteum is colored as a result of concentrating carotenoids (including lutein) from the diet and secretes a moderate amount of estrogen to inhibit further release of gonadotropin-releasing hormone (GnRH) and thus secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). A new corpus luteum develops with each menstrual cycle.


Fish are gill-bearing aquatic craniate animals that lack limbs with digits. They form a sister group to the tunicates, together forming the olfactores. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Tetrapods emerged within lobe-finned fishes, so cladistically they are fish as well. However, traditionally fish are rendered paraphyletic by excluding the tetrapods (i.e., the amphibians, reptiles, birds and mammals which all descended from within the same ancestry). Because in this manner the term "fish" is defined negatively as a paraphyletic group, it is not considered a formal taxonomic grouping in systematic biology, unless it is used in the cladistic sense, including tetrapods. The traditional term pisces (also ichthyes) is considered a typological, but not a phylogenetic classification.

The earliest organisms that can be classified as fish were soft-bodied chordates that first appeared during the Cambrian period. Although they lacked a true spine, they possessed notochords which allowed them to be more agile than their invertebrate counterparts. Fish would continue to evolve through the Paleozoic era, diversifying into a wide variety of forms. Many fish of the Paleozoic developed external armor that protected them from predators. The first fish with jaws appeared in the Silurian period, after which many (such as sharks) became formidable marine predators rather than just the prey of arthropods.

Most fish are ectothermic ("cold-blooded"), allowing their body temperatures to vary as ambient temperatures change, though some of the large active swimmers like white shark and tuna can hold a higher core temperature.Fish can communicate in their underwater environments through the use of acoustic communication. Acoustic communication in fish involves the transmission of acoustic signals from one individual of a species to another. The production of sounds as a means of communication among fish is most often used in the context of feeding, aggression or courtship behaviour. The sounds emitted by fish can vary depending on the species and stimulus involved. They can produce either stridulatory sounds by moving components of the skeletal system, or can produce non-stridulatory sounds by manipulating specialized organs such as the swimbladder.Fish are abundant in most bodies of water. They can be found in nearly all aquatic environments, from high mountain streams (e.g., char and gudgeon) to the abyssal and even hadal depths of the deepest oceans (e.g., gulpers and anglerfish), although no species has yet been documented in the deepest 25% of the ocean. With 33,600 described species, fish exhibit greater species diversity than any other group of vertebrates.Fish are an important resource for humans worldwide, especially as food. Commercial and subsistence fishers hunt fish in wild fisheries (see fishing) or farm them in ponds or in cages in the ocean (see aquaculture). They are also caught by recreational fishers, kept as pets, raised by fishkeepers, and exhibited in public aquaria. Fish have had a role in culture through the ages, serving as deities, religious symbols, and as the subjects of art, books and movies.

Fish physiology

Fish physiology is the scientific study of how the component parts of fish function together in the living fish. It can be contrasted with fish anatomy, which is the study of the form or morphology of fishes. In practice, fish anatomy and physiology complement each other, the former dealing with the structure of a fish, its organs or component parts and how they are put together, such as might be observed on the dissecting table or under the microscope, and the later dealing with how those components function together in the living fish.

Fish reproduction

Fish reproductive organs include testes and ovaries. In most species, gonads are paired organs of similar size, which can be partially or totally fused. There may also be a range of secondary organs that increase reproductive fitness. The genital papilla is a small, fleshy tube behind the anus in some fishes, from which the sperm or eggs are released; the sex of a fish often can be determined by the shape of its papilla.


Although the process is similar in many animals, this article will deal exclusively with human folliculogenesis.

In biology, folliculogenesis is the maturation of the ovarian follicle, a densely packed shell of somatic cells that contains an immature oocyte. Folliculogenesis describes the progression of a number of small primordial follicles into large preovulatory follicles that occurs in part during the menstrual cycle.

Contrary to male spermatogenesis, which can last indefinitely, folliculogenesis ends when the remaining follicles in the ovaries are incapable of responding to the hormonal cues that previously recruited some follicles to mature. This depletion in follicle supply signals the beginning of menopause.

Grandmother hypothesis

The grandmother hypothesis is a hypothesis to explain the existence of menopause in human life history by identifying the adaptive value of extended kin networking. It builds on the previously postulated "mother hypothesis" which states that as mothers age, the costs of reproducing become greater, and energy devoted to those activities would be better spent helping her offspring in their reproductive efforts. It suggests that by redirecting their energy onto those of their offspring, grandmothers can better ensure the survival of their genes through younger generations. By providing sustenance and support to their kin, grandmothers not only ensure that their genetic interests are met, but they also enhance their social networks which could translate into better immediate resource acquisition. This effect could extend past kin into larger community networks and benefit wider group fitness.

List of MeSH codes (G08)

The following is a list of the "G" codes for MeSH. It is a product of the United States National Library of Medicine.

Source for content is here. (File "2006 MeSH Trees".)


Menopause, also known as the climacteric, is the time in most women's lives when menstrual periods stop permanently, and they are no longer able to bear children. Menopause typically occurs between 49 and 52 years of age. Medical professionals often define menopause as having occurred when a woman has not had any vaginal bleeding for a year. It may also be defined by a decrease in hormone production by the ovaries. In those who have had surgery to remove their uterus but still have ovaries, menopause may be viewed to have occurred at the time of the surgery or when their hormone levels fell. Following the removal of the uterus, symptoms typically occur earlier, at an average of 45 years of age.In the years before menopause, a woman's periods typically become irregular, which means that periods may be longer or shorter in duration or be lighter or heavier in the amount of flow. During this time, women often experience hot flashes; these typically last from 30 seconds to ten minutes and may be associated with shivering, sweating, and reddening of the skin. Hot flashes often stop occurring after a year or two. Other symptoms may include vaginal dryness, trouble sleeping, and mood changes. The severity of symptoms varies between women. While menopause is often thought to be linked to an increase in heart disease, this primarily occurs due to increasing age and does not have a direct relationship with menopause. In some women, problems that were present like endometriosis or painful periods will improve after menopause.Menopause is usually a natural change. It can occur earlier in those who smoke tobacco. Other causes include surgery that removes both ovaries or some types of chemotherapy. At the physiological level, menopause happens because of a decrease in the ovaries' production of the hormones estrogen and progesterone. While typically not needed, a diagnosis of menopause can be confirmed by measuring hormone levels in the blood or urine. Menopause is the opposite of menarche, the time when a girl's periods start.Specific treatment is not usually needed. Some symptoms, however, may be improved with treatment. With respect to hot flashes, avoiding smoking, caffeine, and alcohol is often recommended. Sleeping in a cool room and using a fan may help. The following medications may help: menopausal hormone therapy (MHT), clonidine, gabapentin, or selective serotonin reuptake inhibitors. Exercise may help with sleeping problems. While MHT was once routinely prescribed, it is now only recommended in those with significant symptoms, as there are concerns about side effects. High-quality evidence for the effectiveness of alternative medicine has not been found. There is tentative evidence for phytoestrogens.

Ovarian follicle activation

Ovarian follicle activation can be defined as primordial follicles in the ovary moving from a quiescent (inactive) to a growing phase. The primordial follicle in the oocyte is what makes up the “pool” of follicles that will be induced to enter growth and developmental changes that change them into pre-ovulatory follicles, ready to be released during ovulation. The process of development from a primordial follicle to a pre-ovulatory follicle is called folliculogenesis.

Activation of the primordial follicle involves the following: a morphological change from flattened to cuboidal granulosa cells, proliferation of granulosa cells, formation of the protective zona pellucida layer, and growth of the oocyte.It is widely understood that androgens act primarily on preantral follicles and that this activity is important for preantral follicle growth. Additionally, it is thought that androgens are involved in primordial follicle activation. However, the influence of androgens on primordial follicle recruitment and whether this response is primary or secondary is still uncertain.

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