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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.[1][2]

Article Draft

Overview

Follicular atresia is the breakdown of the ovarian follicles which are made in mammalian ovaries in order to secrete hormones and oocytes. Oocytes are immature eggs and are surrounded by granulosa cells and internal and external theca cells.[3]Oocytes are then able to mature within the follicle through meiosis. However, in female humans, this process occurs continuously, as they are born with a finite number of follicles (between 500,000-1,000,000 follicles), and about 99% of follicles undergo atresia[4]. Only one follicle will be mature enough to release an egg and may be fertilized[5]. Typically, around 20 follicles mature each month, but only a single follicle is ovulated; the follicle from the oocyte was released becomes the corpus luteum. The corpus luteum is the last stage of the ovarian follicles' lifecycle. It has an important role in secreting estrogen and progesterone to prepare the body for conception. If conception does not occur, then it will be shed and is known as the corpus albicans[6]. It has been observed that this mechanism is important in regulating and maintaining a healthy reproductive system in mammals. It is also a subject of interest in understanding and predicting fertility in female humans.

Mechanism

Atresia is a complex, hormonally controlled apoptotic process that depends dominantly on granulosa cell apoptosis. Follicular atresia is inhibited by follicle-stimulating hormone (FSH), which promotes follicle development. Once the follicle has developed, it secretes estrogen, which in high levels decreases secretions of FSH. Granulosa cell apoptosis is considered the underlying mechanism of follicular atresia, and has been associated with five ligand-receptor systems involved in cell death: [3]

Granulosa cell apoptosis is induced by tumor necrosis factor-alpha (TNFα), although the mechanism of how it occurs is unclear.[7]

Fas antigen, a cell surface receptor protein, is expressed on granulosa cells and helps mediate signals that induce apoptosis by binding Fas ligand and therefore plays an important role in follicular atresia.[8] Lack of a working Fas ligand / Fas receptor system has been linked to abnormal follicle development, and increased secondary follicles as a result of the inability to induce apoptosis.

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

Two intracellular inhibitor proteins, cellular FLICE-like inhibitory protein short form (cFLIPS) and long form (cFLIPL), which are expressed in granulosa cells, may be anti-apoptotic factors.[10]

Undergoing follicular atresia is necessary in order for mammals 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.

Morphology

From studying dairy cows, two forms of follicular atresia have been identified: antral and basal.

Antral[11][12]

  • Characterized by the apoptosis of granulosa cells within the antral layers of the granulosa membrane and sometimes within the antrum itself
  • Presence of pyknotic nuclei in antral layers
  • No damage to basal granulosa cells
  • Considered the classic and most commonly observed form of follicular atresia
    • In most species, it occurs throughout follicular development and is universally seen in large follicles

Basal[11][12]

  • Characterized by apoptosis of granulosa cells in the basal layer of the granulosa membrane
  • Often, basal lamina is penetrated by macrophages which phagocytose the basal granulosa cells
  • Also observe an increased deposition of collagen in the theca layer
  • No damage to antral granulosa cells
  • This form of follicular atresia has only been observed in small follicles of dairy cows
    • Not reported in any other species

References

  1. ^ Najati, Vahid; Ilkhanipour, Minoo; Salehi, Shahpar; Sadeghi-Hashjin, Goudarz (2008). "Role of nitric oxide on the generation of atretic follicles in the rat ovaries". Pakistan journal of biological sciences: PJBS. 11 (2): 250–254. doi:10.3923/pjbs.2008.250.254. ISSN 1028-8880. PMID 18817198.
  2. ^ Luo, Yuxin; Zhu, Yanbin; Basang, Wangdui; Wang, Xin; Li, Chunjin; Zhou, Xu (2021). "Roles of Nitric Oxide in the Regulation of Reproduction: A Review". Frontiers in Endocrinology. 12: 752410. doi:10.3389/fendo.2021.752410. ISSN 1664-2392. PMC 8640491. PMID 34867795.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  3. ^ a b Zhou, Jiawei; Peng, Xianwen; Mei, Shuqi (2019). "Autophagy in Ovarian Follicular Development and Atresia". International Journal of Biological Sciences. 15 (4): 726–737. doi:10.7150/ijbs.30369. ISSN 1449-2288. PMC 6429023. PMID 30906205.
  4. ^ Wilkosz, Pawel; Greggains, Gareth D.; Tanbo, Tom G.; Fedorcsak, Peter (2014). "Female Reproductive Decline Is Determined by Remaining Ovarian Reserve and Age". PLoS ONE. 9 (10): e108343. doi:10.1371/journal.pone.0108343. ISSN 1932-6203. PMC 4195570. PMID 25310678.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  5. ^ Zhang, Jinbi; Liu, Yang; Yao, Wang; Li, Qifa; Liu, Honglin; Pan, Zengxiang (2018). "Initiation of follicular atresia: gene networks during early atresia in pig ovaries". Reproduction. 156 (1): 23–33. doi:10.1530/REP-18-0058. ISSN 1741-7899.
  6. ^ Kirkendoll, Shelbie D.; Bacha, Dhouha (2022), "Histology, Corpus Albicans", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31424854, retrieved 2022-07-26
  7. ^ Yamamoto, Yuri; Kuwahara, Akira; Taniguchi, Yuka (2015). "Tumor necrosis factor alpha inhibits ovulation and induces granulosa cell death in rat ovaries". Reproductive Medicine and Biology. 14 (3): 107–115. doi:10.1007/s12522-014-0201-5. PMC 4490172. PMID 26161038.{{cite journal}}: CS1 maint: PMC format (link)
  8. ^ Yang, Runjun; Xu, Shangzhong; Zhao, Zhihui; Li, Junya (2012). "Fas ligand expression and mediated activation of an apoptosis program in bovine follicular granulosa cells". Gene. 493 (1): 148–154. doi:10.1016/j.gene.2011.11.032.
  9. ^ Naimi, Adel; Movassaghpour, Ali Akbar; Hagh, Majid Farshdousti (2018). "TNF-related apoptosis-inducing ligand (TRAIL) as the potential therapeutic target in hematological malignancies". Biomedicine & Pharmacotherapy. 98: 566–576. doi:10.1016/j.biopha.2017.12.082. ISSN 0753-3322.
  10. ^ Manabe, Noboru; Goto, Yasufumi; Matsuda-Minehata, Fuko; Inoue, Naoko (2004). "Regulation Mechanism of Selective Atresia in Porcine Follicles: Regulation of Granulosa Cell Apoptosis during Atresia". Journal of Reproduction and Development. 50 (5): 493–514. doi:10.1262/jrd.50.493. ISSN 0916-8818.
  11. ^ a b Makarevich, Alexander V.; Földešiová, Martina; Pivko, Juraj; Kubovičová, Elena; Chrenek, Peter (2018). "Histological characteristics of ovarian follicle atresia in dairy cows with different milk production". Anatomia, Histologia, Embryologia. 47 (6): 510–516. doi:10.1111/ahe.12389.
  12. ^ a b H., David; M.H., Catherine (2012), Darwish, Atef (ed.), "Ovarian Follicular Atresia", Basic Gynecology - Some Related Issues, InTech, doi:10.5772/32465, ISBN 978-953-51-0166-6, retrieved 2022-07-26