Development of chromaffin modules during postnatal ontogenesis

Abstract

BACKGROUND: The principle of modularity, which implies organization based on morphofunctional units, is a fundamental feature of living systems at all levels. It has only recently been established that the adrenal medulla comprises adrenaline-producing (A) and noradrenaline-producing (NA) modules, raising questions about the ontogenetic development of these structures.

AIM: To investigate the postnatal development of chromaffin modules in the adrenal medulla.

METHODS: A cross-sectional, observational, non-controlled study was conducted on adrenal medulla samples from rats. To reliably identify A and NA cells and evaluate the structure of the modules they form, adrenal tissue specimens were processed using the Onore method and conventional protocols recommended for transmission electron microscopy.

RESULTS: Adrenal glands from rats were examined at the following postnatal ages: newborn, 6–8 days, 14 days, 21 days, 1 month, and 6–8 months. For each age group, 5 to 8 samples were analyzed using each of the two tissue processing methods (n = 80). Adrenal medullae of adult rats contain mature A and NA modules. A-modules are rounded complexes of tightly packed A-cells, with characteristic expanded intercellular spaces at the center. NA-modules consist of more loosely associated NA-cells, forming ampullary intercellular enlargements and merging into large polygonal arrays. Polygonal NA-modules tend to interpose between rounded A-modules. Each chromaffin cell is found exclusively within a module of its respective type. In newborn rats, the adrenal medulla contains rounded complexes of chromaffinoblasts referred to as medullary spheres. Most of these complexes consist of tightly packed, electron-lucent cells, although some less rounded complexes of more electron-dense and loosely arranged cells are also observed. These features suggest that medullary spheres represent precursors of A and NA modules. By postnatal days 6–8, chromaffinoblasts differentiate into A and NA cells, each forming modules of their respective type, which already display characteristic features: rounded shape, compact arrangement, and central intercellular spaces for A-modules; polygonal shape and looser intercellular contacts with ampullary expansions for NA-modules. These morphological distinctions become more pronounced with age. The size of both module types increases linearly throughout the postnatal period. A-modules maintain a compact, slightly elongated ellipsoid shape, whereas NA-modules and the arrays they form become increasingly angular and extended. These changes are particularly active between postnatal days 14–21 and from 1 to 8 months of age, reflecting overall growth patterns of chromaffin tissue in the adrenal medulla.

CONCLUSION: The simultaneous appearance of A and NA modules alongside the differentiation of chromaffinoblasts into A and NA cells, as well as the morphological features of their formation, support the concept of modular organization as the morphofunctional basis of the adrenal medulla.

Keywords

adrenal medulla / adrenalocytes / noradrenalocytes / chromaffin system / chromaffin cells

References

[1] Danilov RK. General principles of cellular organization, development and classification of tissues. In: Danilov RK, editor. Manual of Histology. 2nd ed. Saint Petersburg: SpetsLit; 2010. P:98–123. (In Russ.)

[2] Kemoklidze KG. Morphofunctional units of an organ: history and modern state of the question. Morphology. 2019;156(5):93–97. (In Russ.) EDN: MNYOYJ

[3] Kemoklidze KG, Tyumina NA. Rat adrenal medulla modular organization. RUDN Journal of Medicine. 2022;26(3):259–273. doi: 10.22363/2313-0245-2022-26-3-259-273 EDN: QVRLKF

[4] Honoré LH. A light microscopic method for the differentiation of noradrenaline and adrenaline producing cells of the rat adrenal medulla. J Histochem Cytochem. 1971;19(8):483–486. doi: 10.1177/19.8.483

[5] Coupland RE. Ultrastructural features of the mammalian adrenal medulla. In: P. Motta, editor. Ultrastructure of Endocrine Cells and Tissues. New York: Springer New York; 1984. P:168–179. doi: 10.1007/978-1-4613-3861-1_15

[6] Zapadnyuk IP, Zapadnyuk VI, Zakharia EA Laboratory animals. Breeding, housing, use in experiments. 3rd ed. Kyiv: Vyscha shkola; 1983. (In Russ.)

[7] Wiesel J. Über die Entwicklung der Nebennicra des Schweines, besondcrs dor Marksubstanz. Anatomische Hefte. 1901;16:115–150. (In German)

[8] Katznelson ZS, Stabrovsky EM. Histology and biochemistry of chromaffin tissue of the adrenal glands. Leningrad: Medicina; 1975. (In Russ.)

[9] Smitten NA The sympathoadrenal system in the phylo- and ontogenesis of vertebrates. Moscow: Nauka; 1972. (In Russ.)

[10] Chumasov EI, Atagimov MZ, Sokolov VI, Seliverstova VG, Development of adrenal chromaffin tissue. Morphology. 2003;123(3):68–73. EDN: WLMDAB

[11] Coupland RE, Tomlinson A. The development and maturation of adrenal medullary chromaffin cells of the rat in vivo: A descriptive and quantitative study. Int J Dev Neurosci. 1989;7(5):419–438. doi: 10.1016/0736-5748(89)90003-8

[12] Pavlov AV, Kemoklidze KG. Cytologic mechanisms of postnatal growth of adrenal chromaffin tissue. Ontogenez. 1998;29(2):123–128. (In Russ.) EDN: MOZQOD

[13] Verhofstad AAJ, Coupland RE, Parker TR, Goldstein M. Immunohistochemical and biochemical study on the development of the noradrenaline- and adrenaline-storing cells of the adrenal medulla of the rat. Cell Tissue Res. 1985;242(2):233–243. doi: 10.1007/BF00214536 EDN: BOCENA

[14] Léon C, Grant N, Aunis D, Langley K. L1 Cell Adhesion Molecule is Expressed by Noradrenergic but not Adrenergic Chromaffin Cells: A Possible Major Role for L1 in Adrenal Medullary Design. Eur J Neurosci. 1992;4(3):201–209. doi: 10.1111/j.1460-9568.1992.tb00868.x

[15] Zaika OL, Pochynyuk OM, Yavorskaya EN, et al. Acetylcholine-induced calcium signalling in adrenaline- and noradrenaline-containing adrenal chromaffin cells. Arch Biochem Biophys. 2004;424(1):23–32. doi: 10.1016/j.abb.2004.01.012 EDN: XJSORN

[16] Oomori Y, Habara Y, Kanno T. Muscarinic and nicotinic receptor-mediated Ca 2+ dynamics in rat adrenal chromaffin cells during development. Cell Tissue Res. 1998;294(1):109–123. doi: 10.1007/s004410051161 EDN: ATHOGX

[17] Kemoklidze KG, Tyumina NA, Leonenko PS. 3D reconstruction of the rat adrenal medulla. Anat Histol Embryol. 2021;50(5):781–787. doi: 10.1111/ahe.12720 EDN: SKWHML

[18] Kemoklidze KG, Tyumina NA. 3D organization of the rat adrenal medulla. In: Vitamins and Hormones. San Diego: Academic Press; 2024. P:367–392. doi: 10.1016/bs.vh.2023.06.003

[19] Kadmon G, Kowitz A, Altevogt P, Schachner M. The neural cell adhesion molecule N-CAM enhances L1-dependent cell-cell interactions. J Cell Biol. 1990;110(1):193–208. doi: 10.1083/jcb.110.1.193

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