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an abnormal condition in which a normal opening or tube in the body (as the urethra) is closed or absent
of or relating to or constituting a follicle

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/10 22:56:12」(JST)

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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]

Mechanism

Follicular atresia is inhibited by follicle-stimulating hormone (FSH), which promotes follicle development.^[3] Once the follicle has developed, it secretes estrogen, which in high levels decreases secretions of FSH.^[4] Granulosa cell apoptosis is considered the underlying mechanism of follicular atresia, and has been associated with five ligand-receptor systems involved in cell death:^[5]

Tumor necrosis factor-alpha (TNFα) and receptors
Fas ligand and receptors
TNF-related apoptosis-inducing ligand (TRAIL or APO-2) and receptors
APO-3 ligand and receptors
PFG-5 ligand and receptors

Granulosa cell apoptosis is promoted by tumor necrosis factor-alpha (TNFα), though the mechanism of TNFα is unclear.^[6]^[7]

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.^[8]

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.^[9]

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.^[10]

References

^ [Faddy, M. J. "Follicle dynamics during ovarian ageing." Molecular and cellular endocrinology 163.1 (2000): 43-48.]
^ [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.]
^ [Kaipia, Antti, and Aaron JW Hsueh. "Regulation of ovarian follicle atresia." Annual review of physiology 59.1 (1997): 349-363.]
^ [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.]
^ [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.]
^ [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.]
^ [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.]
^ [Sakamaki, Kazuhiro, et al. "Involvement of Fas antigen in ovarian follicular atresia and luteolysis." Molecular reproduction and development 47.1 (1997): 11-18.]
^ [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.]
^ [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.]

UpToDate Contents

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1. 健常女性における卵巣の発達および機能不全（閉経） ovarian development and failure menopause in normal women
2. 乳房の発達および形態 breast development and morphology

English Journal

Pathways of the dominant follicle after exposure to sub-luteal circulating progesterone concentrations are different in lactating dairy cows versus non-lactating heifers.

Atanasov B1, De Koster J2, Bommelé L3, Dovenski T4, Opsomer G5.
Animal reproduction science.Anim Reprod Sci.2015 Mar;154:8-15. doi: 10.1016/j.anireprosci.2015.01.002. Epub 2015 Jan 19.
With the increased use of different synchronization programs in cattle, attention is given to the progesterone concentration during development of the ovulatory follicle. It has been shown that low peripheral progesterone concentrations during follicular development may lead to decreased fertility.
PMID 25637465

Assessment of the health status of wild fish inhabiting a cotton basin heavily impacted by pesticides in Benin (West Africa).

Agbohessi PT1, Imorou Toko I2, Ouédraogo A3, Jauniaux T4, Mandiki SN5, Kestemont P5.
The Science of the total environment.Sci Total Environ.2015 Feb 15;506-507:567-84. doi: 10.1016/j.scitotenv.2014.11.047. Epub 2014 Nov 27.
To determine the impact of agricultural pesticides used in cotton cultivation on the health status of fish living in a Beninese cotton basin, we compared the reproductive and hepatic systems of fish sampled from rivers located in both contaminated and pristine conditions. Different types of biomarke
PMID 25433386

Effects of dehydroepiandrosterone (DHEA) on follicular dynamics in a diminished ovarian reserve in vivo model.

Hassa H1, Aydin Y, Ozatik O, Erol K.
Systems biology in reproductive medicine.Syst Biol Reprod Med.2015 Feb 11:1-5. [Epub ahead of print]
Abstract The objective of this study was to determine whether there are changes in primary, primordial, and growing follicles after dehydroepiandrosterone (DHEA) administration in rats that have diminished ovarian reserve (DOR) due to 4-vinylcyclohexene diepoxide (VCD) application, and to examine th
PMID 25671506

Japanese Journal

Follicular Growth and Atresia in Mammalian Ovaries : Regulation by Survival and Death of Granulosa Cells

MATSUDA Fuko,INOUE Naoko,MANABE Noboru [他],OHKURA Satoshi
The Journal of reproduction and development 58(1), 44-50, 2012-02-01
… Due to the numerous efforts of researchers, mechanisms regulating follicular growth and atresia in mammalian ovaries have been clarified, not only their systemic regulation by hormones (gonadotropins) but also their intraovarian regulation by gonadal steroids, growth factors, cytokines and intracellular proteins. …
NAID 10030407021

Does 2-hydroxyflutamide Inhibit Apoptosis in Porcine Granulosa Cells? — An In Vitro Study

DUDA Malgorzata,DURLEJ Malgorzata,KNET Malgorzata [他],KNAPCZYK-STWORA Katarzyna,TABAROWSKI Zbigniew,SLOMCZYNSKA Maria
Journal of Reproduction and Development 58(4), 438-444, 2012
… In mammalian ovaries, the majority of follicles are lost before ovulation by atresia. … To reveal the androgen-dependent mechanism of selective follicular atresia, the culture model system for agonism and antagonism of the androgen receptor has been established. … Follicles cultured with the addition of T or 2-Hf exhibited morphological changes indicating follicular atresia. …
NAID 130001854974

Effect of RNA Interference of BID and BAX mRNAs on Apoptosis in Granulosa Cell-derived KGN Cells

SAI Takafumi,MATSUDA Fuko,GOTO Yasufumi [他],MAEDA Akihisa,SUGIMOTO Miki,GAO Hong-Mei,KABIR Abul Khair Mohammad Ahan,LI Jun-You,MANABE Noboru
Journal of Reproduction and Development 58(1), 112-116, 2012
… In porcine ovaries, the levels of BID and BAX increase in follicular granulosa cells during atresia. …
NAID 130001388599