Summary
The localization of epidermal-type fatty acid binding protein (E-FABP) in the mature mouse ovary was examined by immuno-light and electron microscopy. Numerous macrophages immunopositive for both anti-E-FABP and F4/80 antibodies, together with immunonegative cells, were found in advanced atretic follicles that had eccentric lumens containing deformed ova. While some E-FABP-immunopositive macrophages were spider in shape and appeared singly, others, especially close to the lumen, were round and voluminous and tended to be aggregated. The voluminous macrophages contained phagosomes of various sizes and they were regarded as those actively involved in the phagocytosis of apoptotic granulosa cells. E-FABP-immunopositive macrophages and their processes were often apposed to adjacent immunonegative cells, and some of them lined the lumen containing deformed ova. On the other hand, E-FABP-immunonegative cells in the atretic follicles were classified into two types: the one, a minority, was characterized by small mitochondria containing non-tubular cristae and presumably represented residual granulosa cells, while the other dominant type was characterized by large mitochondria containing tubular cristae and presumably represented theca cells originally surrounding the follicles to be atretic. The present detection of E-FABP-immunopositivity selectively in macrophages of the atretic follicles suggests possible involvement of E-FABP and/or its ligand fatty acids in the process of follicular atresia, and it makes more reliable the identification of the advanced atretic follicles with the antral spaces obliterated, which could provide further details on the histology of the follicular atresia than before.
Similar content being viewed by others
References
Alpers DH, Strauss AW, Ockner RK, Bass NM, Gordon JI (1984) Cloning of a cDNA encoding rat intestinal fatty acid binding protein. Proc Natl Acad Sci U S A 81:313–317
Bjersing L (1982) Maturation, morphology, and endocrine function of the ovarian follicle. Adv Exp Med Biol 147:1–14
Blondin P, Dufour M, Sirard MA (1996) Analysis of atresia in bovine follicles using different methods: flow cytometry, enzyme-linked immunosorbent assay, and classic histology. Biol Reprod 54:631–637
Borchers T, Spener F (1993) Involvement of arginine in the binding of heme and fatty acids to fatty acid-binding protein from bovine liver. Mol Cell Biochem 123:23–27
Coe NR, Bernlohr DA (1998) Physiological properties and functions of intracellular fatty acid-binding proteins. Biochim Biophys Acta 1391:287–306
Cohen PE, Nishimura K, Zhu L, Pollard JW (1999) Macrophages: important accessory cells for reproductive function. J Leukoc Biol 66:765–772
Fels AO, Pawlowski NA, Abraham EL, Cohn ZA (1986) Compartmentalized regulation of macrophage arachidonic acid metabolism. J Exp Med 163:752–757
Feng L, Hatten ME, Heintz N (1994) Brain lipid-binding protein (BLBP): a novel signaling system in the developing mammalian CNS. Neuron 12:895–908
Gordon JI, Alpers DH, Ockner RK, Strauss AW (1983) The nucleotide sequence of rat liver fatty acid binding protein mRNA. J Biol Chem 258:3356–3363
Guthmann F, Hohoff C, Fechner H, Humbert P, Borchers T, Spener F, Rustow B (1998) Expression of fatty-acid-binding proteins in cells involved in lung-specific lipid metabolism. Eur J Biochem 253:430–436
Hirshfield AN, Midgley AR Jr. (1978) Morphometric analysis of follicular development in the rat. Biol Reprod 19:597–605
Hughes FM Jr., Gorospe WC (1991) Biochemical identification of apoptosis (programmed cell death) in granulosa cells: evidence for a potential mechanism underlying follicular atresia. Endocrinology 129:2415–2422
Hume DA, Halpin D, Charlton H, Gordon S (1984) The mononuclear phagocyte system of the mouse defined by immunohistochemical localization of antigen F4/80: macrophages of endocrine organs. Proc Natl Acad Sci U S A 81:4174–4177
Hunt CR, Ro JH, Dobson DE, Min HY, Spiegelman BM (1986) Adipocyte P2 gene: developmental expression and homology of 5’-flanking sequences among fat cell-specific genes. Proc Natl Acad Sci U S A 83:3786–3790
Inoue S, Watanabe H, Saito H, Hiroi M, Tonosaki A (2000) Elimination of atretic follicles from the mouse ovary: a TEM and immunohistochemical study in mice. J Anat 196(Pt 1):103–110
Jaworski C, Wistow G (1996) LP2, a differentiation-associated lipid-binding protein expressed in bovine lens. Biochem J 320(Pt 1):49–54
Kamo A, Araki Y, Maeda K, Watanabe H (2004) Characteristics of invasive cells found in between zona pellucida and oocyte during follicular atresia in mice. Zygote 12:269–276
Kitanaka N, Owada Y, Abdelwahab SA, Iwasa H, Sakagami H, Watanabe M, Spener F, Kondo H (2003) Specific localization of epidermal-type fatty acid binding protein in dendritic cells of splenic white pulp. Histochem Cell Biol 120:465–473
Kruip TA, Dieleman SJ (1982) Macroscopic classification of bovine follicles and its validation by micromorphological and steroid biochemical procedures. Reprod Nutr Dev 22:465–473
Kurtz A, Zimmer A, Schnutgen F, Bruning G, Spener F, Muller T (1994) The expression pattern of a novel gene encoding brain-fatty acid binding protein correlates with neuronal and glial cell development. Development 120:2637–2649
Li XQ, Itoh M, Yano A, Xie Q, Miyamoto K, Takeuchi Y (1998) Distribution of F4/80-positive cells in developing ovaries in the mouse. Arch Histol Cytol 61:353–360
Masouye I, Hagens G, Van Kuppevelt TH, Madsen P, Saurat JH, Veerkamp JH, Pepper MS, Siegenthaler G (1997) Endothelial cells of the human microvasculature express epidermal fatty acid-binding protein. Circ Res 81:297–303
O’Shaughnessy RF, Seery JP, Celis JE, Frischauf A, Watt FM (2000) PA-FABP, a novel marker of human epidermal transit amplifying cells revealed by 2D protein gel electrophoresis and cDNA array hybridisation. FEBS Lett 486:149–154
Owada Y, Abdelwahab SA, Suzuki R, Iwasa H, Sakagami H, Spener F, Kondo H (2001) Localization of epidermal-type fatty acid binding protein in alveolar macrophages and some alveolar type II epithelial cells in mouse lung. Histochem J 33:453–457
Owada Y, Suzuki R, Iwasa H, Spener F, Kondo H (2002a) Localization of epidermal-type fatty acid binding protein in the thymic epithelial cells of mice. Histochem Cell Biol 117:55–60
Owada Y, Takano H, Yamanaka H, Kobayashi H, Sugitani Y, Tomioka Y, Suzuki I, Suzuki R, Terui T, Mizugaki M, Tagami H, Noda T, Kondo H (2002b) Altered water barrier function in epidermal-type fatty acid binding protein-deficient mice. J Invest Dermatol 118:430–435
Owada Y, Yoshimoto T, Kondo H (1996) Spatio-temporally differential expression of genes for three members of fatty acid binding proteins in developing and mature rat brains. J Chem Neuroanat 12:113–122
Petrovska M, Dimitrov DG, Michael SD (1996) Quantitative changes in macrophage distribution in normal mouse ovary over the course of the estrous cycle examined with an image analysis system. Am J Reprod Immunol 36:175–183
Siegenthaler G, Hotz R, Chatellard-Gruaz D, Jaconi S, Saurat JH (1993) Characterization and expression of a novel human fatty acid-binding protein: the epidermal type (E-FABP). Biochem Biophys Res Commun 190:482–487
Simon C, Frances A, Piquette G, Polan ML (1994) Immunohistochemical localization of the interleukin-1 system in the mouse ovary during follicular growth, ovulation, and luteinization. Biol Reprod 50:449–457
Stern J, Coulam CB (1992) New concepts in ovarian regulation: an immune insight. Am J Reprod Immunol 27:136–144
Tilly JL, Kowalski KI, Johnson AL, Hsueh AJ (1991) Involvement of apoptosis in ovarian follicular atresia and postovulatory regression. Endocrinology 129:2799–2801
Watanabe M, Ono T, Kondo H (1991) Immunohistochemical studies on the localisation and ontogeny of heart fatty acid binding protein in the rat. J Anat 174:81–95
Wen Y, Li GW, Chen P, Wong E, Bekhor I (1995) Lens epithelial cell mRNA, II. Expression of a mRNA encoding a lipid-binding protein in rat lens epithelial cells. Gene 158:269–274
Acknowledgements
This study was supported by grants from the Ministry of Education, Science, Culture and Sports to H. Kondo (Number 14657623) and to Y. Owada (Number 14580720) and by the grant from HIROMI Medical Research Foundation to Y. Owada. M.R. Nourani is a recipient of the predoctoral fellowship from Medical School of Baghiyatollah University, Teheran, Iran.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Nourani, M.R., Owada, Y., Kitanaka, N. et al. Localization of epidermal-type fatty acid binding protein in macrophages in advanced atretic follicles of adult mice. J Mol Hist 36, 391–400 (2005). https://doi.org/10.1007/s10735-005-9005-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-005-9005-6