Advertisement

Follicular Cells

  • María Luisa EscobarEmail author
  • Gerardo H. Vázquez-Nin
  • Olga M. Echeverría
Chapter

Abstract

Atresia occurs in neonate, as well as in prepubertal organisms, the ­follicles that reach the antral follicular phase will inevitably be eliminated as a ­consequence of diverse causes as the absence of the hormone source present once the organism reach puberty. Most follicles appear to undergo atresia at an earlier stage of growth. Basal concentration of gonadotropins appears sufficient to maintain follicle growth to small antral stage only. Prepubertal mice ovaries possess a mixture of late preantral and early antral follicles destined to atresia due to inadequate gonadotropin support prior to puberty. Therefore, before the onset of puberty, the normal fate of growing follicles is atretic demise. Observations of the ovary atresia demonstrated that in neonate and prior to puberty most atresia occurs in preantral follicles.

Keywords

Granulosa Cell Antral Follicle Primordial Follicle Follicular Development Preantral Follicle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of Abbreviations

LH

Luteinizing hormone

FSH

Follicle stimulant hormone

TGFβ

Transforming growth factor beta

EGF

Epidermal growth factor

TUNEL

Terminal Deoxy-UTP nick end labeling. Procedure that detects DNA breaks

Apaf-1

Apoptotic protease activating factor 1

ALK7

Activin receptor-like kinase 7

bFGF

Basic fibroblast growth factor

Bcl-2

B-cell lymphoma 2

Bok

Bcl-2-related ovarian killer

cAMP

Cyclic adenosine monophosphate

DAPI

4’,6-Diamidino-2-phenylindole

DES

Diethylstilbestrol

eGC

Equine chorionic gonadotropin

Fas-L

Fas ligand

FLIPs

Flice-like inhibitory protein isoform

FSHR

Follicle stimulant hormone-receptor

Hiap-2

Human inhibitor of apoptosis protein-2

IAPs

Inhibitor of apoptosis proteins

IGF-1

Insulin-like growth factor-I

IL-1β

Interleukin-1β

NO

Nitric oxide

NFκB

Nuclear factor κB

PMSG

Pregnant mare serum gonadotropin

ROS

Reactive oxygen species

TNFα

Tumor necrosis factor-alpha

Xiap

X-link inhibitor of apoptosis protein

References

  1. Asselin E, Wang Y, Tsang BK (2001) X-linked inhibitor of apoptosis protein activates the ­phosphatidylinositol 3-kinase/Akt pathway in rat granulosa cells during follicular development. Endocrinology 142(6):2451–2457PubMedCrossRefGoogle Scholar
  2. Billig H, Furuta I, Hsueh AJW (1993) Estrogens inhibit and androgens enhance ovarian granulosa cell apoptosis. Endocrinology 133:2204–2212PubMedCrossRefGoogle Scholar
  3. Boone DL, Tsang BK (1998) Caspase-3 in the rat ovary: localization and possible role in follicular atresia and luteal regression. Biol Reprod 58:1533–1539PubMedCrossRefGoogle Scholar
  4. Britt KL, Drummond AE, Dyson M, Wreford NG, Jones ME, Simpson ER et al (2001) The ­ovarian phenotype of the aromatase knockout (ArKO) mouse. J Steroid Biochem Mol Biol 79:181–185PubMedCrossRefGoogle Scholar
  5. Carson RS, Findlay JK, Clarke IJ, Burger HG (1981) Estradiol, testosterone, and androstenedione in ovine follicular fluid during growth and atresia of ovarian follicles. Biol Reprod 24:105–13PubMedCrossRefGoogle Scholar
  6. Chen Q, Yano T, Matsumi H, Osuga Y, Yano N, Xu J et al (2005) Cross-talk between Fas/Fas ligand system and nitric oxide in the pathway subserving granulosa cell apoptosis: a possible regulatory mechanism for ovarian follicle atresia. Endocrinology 146:808–815PubMedCrossRefGoogle Scholar
  7. Chun SY, Eisenhauer KM, Minami S et al (1996) Hormonal regulation of apoptosis in early antral follicles: follicle-stimulating hormone as a major survival factor. Endocrinology 137(4):1447–1456PubMedCrossRefGoogle Scholar
  8. Conway BA, Mahesh VB, Mills TM (1990) Effect of dihydrotestosterone on the growth and ­function of ovarian follicles in intact immature females primed with PMSG. J Reprod Fert 90:267–277CrossRefGoogle Scholar
  9. De Felici M (2000) Regulation of primordial germ cell development in the mouse. Int J Dev Biol 44:575–580PubMedGoogle Scholar
  10. Desmeules P, Devine PJ (2006) Characterizing the ovotoxicity of cyclophosphamide metabolites on cultured mouse ovaries. Toxicol Sci 90(2):500–509PubMedCrossRefGoogle Scholar
  11. Dharma SJ, Kelkar RL, Nandedkar TD (2003) Fas and Fas ligand protein and mRNA in normal and atretic mouse ovarian follicles. Reproduction 126:783–789PubMedCrossRefGoogle Scholar
  12. Edwards RG, Fowler RE, Gore-Langton RE, Gosden RG, Jones EC, Readhead C, Steptoe PC (1977) Normal and abnormal follicular growth in mouse, rat and human ovaries. J Reprod Fertil 51:237–263PubMedCrossRefGoogle Scholar
  13. Eisenhauer KM, Chun SY, Billig H, Hsueh AJ (1995) Growth hormone suppression of apoptosis in preovulatory rat follicles and partial neutralization by insulin-like growth factor binding protein. Biol Reprod 53(1):13–20PubMedCrossRefGoogle Scholar
  14. Guigon CJ, Mazaud S, Forest MG, Brailly-Tabard S, Coudouel N, Magre S (2003) Unaltered development of the initial follicular waves and normal pubertal onset in female rats after ­neonatal deletion of the follicular reserve. Endocrinology 144:3651–62PubMedCrossRefGoogle Scholar
  15. Hage AJ, Groen-Klevant AC, Welschen R (1978) Follicle growth in the immature rat ovary. Acta Endocrinol Copenh 88:375–382PubMedGoogle Scholar
  16. Hakuno N, Koji T, Yano T, Kobayashi N, Tsutsumi O, Taketani Y et al (1996) Fas/APO-1/CD95 system as a mediator of granulosa cell apoptosis in ovarian follicle atresia. Endocrinology 137:1938–1948PubMedCrossRefGoogle Scholar
  17. Hillier SG, Ross GT (1979) Effects of exogenous testosterone on ovarian weight, follicular ­morphology and intraovarian progesterone concentration in oestrogen-primed hypophysectomized immature female rats. Biol Reprod 20:261–268PubMedCrossRefGoogle Scholar
  18. Kaipia A, Hsue AJW (1997) Regulation of ovarian follicle atresia. Annu Rev Physiol 59:349–363PubMedCrossRefGoogle Scholar
  19. Kaipia A, Chun SY, Eisenhauer K, Hsueh AJ (1996) Tumor necrosis factor-alpha and its second messenger, ceramide, stimulate apoptosis in cultured ovarian follicles. Endocrinology 137:4864–4870PubMedCrossRefGoogle Scholar
  20. Kim JM, Boone DL, Auyeung A, Tsang BK (1998) Granulosa cell apoptosis induced at the ­penultimate stage of follicular development is associated with increased levels of Fas and Fas ligand in the rat ovary. Biol Reprod 58:1170–1176PubMedCrossRefGoogle Scholar
  21. Kim JM, Yoon YD, Tsang BK (1999) Involvement of the Fas/Fas ligand system in p53-mediated granulosa cell apoptosis during follicular development and atresia. Endocrinology 140(5):2307–2317PubMedCrossRefGoogle Scholar
  22. Kondo H, Maruo T, Peng X, Mochizuki M (1996) Immunological evidence for the expression of the Fas antigen in the infant and adult human ovary during follicular regression and atresia. J Clin Endocrinol Metab 81:2702–2710PubMedCrossRefGoogle Scholar
  23. Krysko DV, Diez-Fraile A, Criel G, Svistonov AA, Vandenabeele P, D’Herde K (2008) Life and death of female gametes during oogenesis and folliculogenesis. Apoptosis 13:1065–1087PubMedCrossRefGoogle Scholar
  24. Li J, Kim JM, Liston P, Li M, Miyazaki T, Mackenzie AE, Korneluk RG, Tsang BK (1998) Expression of inhibitor of apoptosis proteins (IAPs) in rat granulosa cells during ovarian ­follicular development and atresia. Endocrinology 139:1321–1328PubMedCrossRefGoogle Scholar
  25. McGee EA, Hsueh AJ (2000) Initial and cyclic recruitment of ovarian follicles. Endocr Rev 21(2):200–214PubMedCrossRefGoogle Scholar
  26. Morita Y, Tilly JL (1999) Oocyte apoptosis: like sand through an hourglass. Dev Biol Orlando 214:1–17CrossRefGoogle Scholar
  27. Peluso JJ (2006) Multiplicity of progesterone’s actions and receptors in the mammalian ovary. Biol Reprod 75:2–8PubMedCrossRefGoogle Scholar
  28. Richards JS (1980) Maturation of ovarian follicles: actions and interactions of pituitary and ­ovarian hormones on follicular cell differentiation. Physiol Rev 60(1):51–89PubMedGoogle Scholar
  29. Robles R, Tao XJ, Trbovich AM, Maravei DV, Nhum R, Perez GI, Tilly KI, Tilly JL (1999) Localization, regulation and possible consequences of apoptotic protease-activating factor-1 (Apaf-1) expression in granulosa cells of the mouse ovary. Endocrinology 140(6):2641–4PubMedCrossRefGoogle Scholar
  30. Scaffidi C, Schmitz I, Krammer PH, Peter ME (1999) The role of c-FLIP in modulation of CD95-induced apoptosis. J Biol Chem 274:1541–1548PubMedCrossRefGoogle Scholar
  31. Stocco C (2008) Aromatase expression in the ovary: hormonal and molecular regulation. Steroids 7 3:473–487CrossRefGoogle Scholar
  32. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296–299PubMedCrossRefGoogle Scholar
  33. Terranova PF (1997) Potential roles of tumor necrosis factor-alpha in follicular development, ovulation, and the life span of the corpus luteum. Domest Anim Endocrinol 14:1–15PubMedCrossRefGoogle Scholar
  34. Thompson WE, Powell JM, Whittaker JA, Sridaran R, Thomas KH (1999) Immunolocalization and expression of prohibitin, a mitochondrial associated protein within the rat ovaries. Anat Rec 256:40–48PubMedCrossRefGoogle Scholar
  35. Tilly JL, Tilly KI (1995) Inhibitors of oxidative stress mimic the ability of follicle-stimulating hormone to suppress apoptosis in cultured rat ovarian follicles. Endocrinology 136:242–252PubMedCrossRefGoogle Scholar
  36. Tilly JL, Tilly KL, Kenton ML, Johnson AL (1995) Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis in associated with decreased bax and constitutive bcl-2 and bcl-x long ­messenger RNA levels. Endocrinology 136:232–241PubMedCrossRefGoogle Scholar
  37. Tingen CM, Bristol-Gould SK, Diesewetter SE, Wellington JT, Shea L, Woodruf T (2009b) Prepubertal primordial follicle loss in mice is not due to classical apoptotic pathways. Biol Reprod 81:16–29PubMedCrossRefGoogle Scholar
  38. Tomic D, Brodie SG, Deng C, Hickey RJ, Babus JK, Malkas LH, Flaws JA (2002) Smad3 may regulate follicular growth in the mouse ovary. Biol Reprod 66:917–923PubMedCrossRefGoogle Scholar
  39. Tomic D, Miller KP, Kenny HA, Woodruff TK, Hoyer P, Flaws JA (2004) Ovarian follicle ­development requires Smad3. Mol Endocrinol 18(9):2224–2240PubMedCrossRefGoogle Scholar
  40. Wang H, Jiang JY, Zhu C, Peng C, Tsang BK (2006) Role and regulation of nodal/activin receptor-like kinase 7 signaling pathway in the control of ovarian follicular atresia. Mol Endocrinol 20:2469–2482PubMedCrossRefGoogle Scholar
  41. Williams PC (1940) Effect of stilbestrol on ovaries of hypophysectomized rats. Nature 145:388–389CrossRefGoogle Scholar
  42. Xiao CW, Asselin E, Tsang BK (2002) Nuclear factor kappaBmediated induction of Flice-like inhibitory protein prevents tumor necrosis factor alpha-induced apoptosis in rat granulosa cells. Biol Reprod 67:436–441PubMedCrossRefGoogle Scholar
  43. Zachos NC, Billiar RB, Albrecht ED, Pepe GJ (2002) Developmental regulation of baboon fetal ovarian maturation by estrogen. Biol Reprod 67:1148–1156PubMedCrossRefGoogle Scholar
  44. Zwain I, Amato P (2000) Clusterin protects granulosa cells from apoptotic cell death during ­follicular atresia. Exp Cell Res 257:101–110PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • María Luisa Escobar
    • 1
    Email author
  • Gerardo H. Vázquez-Nin
    • 1
  • Olga M. Echeverría
    • 1
  1. 1.Laboratory of Electron Microscopy, Department of Cell Biology, Faculty of SciencesNational University of Mexico (UNAM)MexicoUSA

Personalised recommendations