seminiferous tubules

Summary

Summary: The convoluted tubules in the TESTIS where sperm are produced (SPERMATOGENESIS) and conveyed to the RETE TESTIS. Spermatogenic tubules are composed of developing germ cells and the supporting SERTOLI CELLS.

Top Publications

  1. Nel Themaat L, Jang C, Stewart M, Akiyama H, Viger R, Behringer R. Sertoli cell behaviors in developing testis cords and postnatal seminiferous tubules of the mouse. Biol Reprod. 2011;84:342-50 pubmed publisher
    Sertoli cells are the primary structural component of the fetal testis cords and postnatal seminiferous tubules. Live imaging technologies facilitate the visualization of cell morphologies and behaviors through developmental processes...
  2. Yang S, Bo J, Hu H, Guo X, Tian R, Sun C, et al. Derivation of male germ cells from induced pluripotent stem cells in vitro and in reconstituted seminiferous tubules. Cell Prolif. 2012;45:91-100 pubmed publisher
    ..However, up to now it is not known whether iPS cells would be able to differentiate into male germ cells in vivo. The aim of this study was to explore differentiation potential of iPS cells to male germ cells in vitro and in vivo...
  3. Bois C, Delalande C, Bouraïma Lelong H, Durand P, Carreau S. 17?-Estradiol regulates cyclin A1 and cyclin B1 gene expression in adult rat seminiferous tubules. J Mol Endocrinol. 2012;48:89-97 pubmed publisher
    ..In order to enlighten the potential role of estrogen in rat spermatogenesis, seminiferous tubules (ST) from two groups of seminiferous epithelium stages (II-VIII and IX-I) were treated with either 17?-..
  4. Sato Y, Nozawa S, Iwamoto T. Study of spermatogenesis and thickening of lamina propria in the human seminiferous tubules. Fertil Steril. 2008;90:1310-2 pubmed publisher
    The negative correlation between the thickness of the lamina propria and Johnsen's score count in individual seminiferous tubules was observed and the tubules with thin lamina propria indicated almost complete spermatogenesis...
  5. Wang Y, Song W, Li S, Guan X, Miao S, Zong S, et al. GC-1 mRHBDD1 knockdown spermatogonia cells lose their spermatogenic capacity in mouse seminiferous tubules. BMC Cell Biol. 2009;10:25 pubmed publisher
    ..GC-1, a spermatogonia cell line, has the capacity to differentiate into spermatids within the seminiferous tubules. We constructed mRHBDD1 knockdown GC-1 cells and evaluated their capacity to differentiate into spermatids ..
  6. Elkin N, Piner J, Sharpe R. Toxicant-induced leakage of germ cell-specific proteins from seminiferous tubules in the rat: relationship to blood-testis barrier integrity and prospects for biomonitoring. Toxicol Sci. 2010;117:439-48 pubmed publisher
    ..Previous studies suggested that disruption of spermatogenesis induced leakage of germ cell proteins from seminiferous tubules (STs) into interstitial fluid (IF); such proteins have potential for use as biomarkers...
  7. Boekelheide K, Kleymenova E, Liu K, Swanson C, Gaido K. Dose-dependent effects on cell proliferation, seminiferous tubules, and male germ cells in the fetal rat testis following exposure to di(n-butyl) phthalate. Microsc Res Tech. 2009;72:629-38 pubmed publisher
    ..Cell proliferation and apoptosis are key processes regulating development of the testis, and alterations in these processes may underlie testicular dysgenesis...
  8. Klein A, Nakagawa T, Ichikawa R, Yoshida S, Simons B. Mouse germ line stem cells undergo rapid and stochastic turnover. Cell Stem Cell. 2010;7:214-24 pubmed publisher
    ..These results suggest that short-lived stem cells may be a common feature of mammalian stem cell systems and reveal a natural mechanism for matching the rates of cell proliferation and loss in tissue...
  9. Boyer A, Hermo L, Paquet M, Robaire B, Boerboom D. Seminiferous tubule degeneration and infertility in mice with sustained activation of WNT/CTNNB1 signaling in sertoli cells. Biol Reprod. 2008;79:475-85 pubmed publisher
    ..mice were sterile because of testicular atrophy starting at 5 wk of age, associated with degeneration of seminiferous tubules and the progressive loss of germ cells...

More Information

Publications63

  1. Satie A, Mazaud Guittot S, Seif I, Mahe D, He Z, Jouve G, et al. Excess type I interferon signaling in the mouse seminiferous tubules leads to germ cell loss and sterility. J Biol Chem. 2011;286:23280-95 pubmed publisher
    ..Type I interferon signaling may lead to idiopathic infertilities by affecting the interplay between germ cells and Sertoli cells...
  2. Perez C, Sobarzo C, Jacobo P, Jarazo Dietrich S, Theas M, Denduchis B, et al. Impaired expression and distribution of adherens and gap junction proteins in the seminiferous tubules of rats undergoing autoimmune orchitis. Int J Androl. 2011;34:e566-77 pubmed publisher
    ..EAO) is characterized by an interstitial lymphomononuclear cell infiltration and a severe lesion of seminiferous tubules (ST) with germ cells that undergo apoptosis and sloughing...
  3. Sasso Cerri E, Cerri P. Morphological evidences indicate that the interference of cimetidine on the peritubular components is responsible for detachment and apoptosis of Sertoli cells. Reprod Biol Endocrinol. 2008;6:18 pubmed publisher
    Cimetidine, referred as antiandrogenic agent, has caused alterations in the seminiferous tubules, including alterations in the peritubular tissue and death of myoid cells by apoptosis...
  4. Schenk R, Jenke A, Zilbauer M, Wirth S, Postberg J. H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes. Chromosoma. 2011;120:275-85 pubmed publisher
    ..H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3...
  5. Takano N, Kimura A, Takahashi T. Two distinct localization patterns of testis-specific serine protease 1 (TESSP1) in the seminiferous tubules of the mouse testis. Zoolog Sci. 2009;26:294-300 pubmed
    ..the wild-type mouse testis, dot-like signals for TESSP1 were observed in the adluminal compartment of the seminiferous tubules, while diffused signals were found in the basal compartment...
  6. Carvalho L, Abreu Silva A, Hardoim D, Tedesco R, Mendes V, da Costa S, et al. Trypanosoma cruzi and myoid cells from seminiferous tubules: interaction and relation with fibrous components of extracellular matrix in experimental Chagas' disease. Int J Exp Pathol. 2009;90:52-7 pubmed publisher
    ..histopathological examination showed alterations in the extracellular matrix of the lamina propria of the seminiferous tubules. Furthermore, amastigotes were present in seminiferous tubules, within myoid cells, and in the adjacencies ..
  7. Oliveira C, Victor Costa A, Hess R. Cellular and regional distributions of ubiquitin-proteasome and endocytotic pathway components in the epithelium of rat efferent ductules and initial segment of the epididymis. J Androl. 2009;30:590-601 pubmed publisher
    ..Localization of ubiquitin-proteasome and endocytotic pathway components suggests that differential regulation is required for protein degradation and turnover in efferent ductules and head of the epididymis...
  8. Kaisman Elbaz T, Sekler I, Fishman D, Karol N, Forberg M, Kahn N, et al. Cell death induced by zinc and cadmium is mediated by clusterin in cultured mouse seminiferous tubules. J Cell Physiol. 2009;220:222-9 pubmed publisher
    Sertoli cells, lining the walls of the seminiferous tubules, are in close contact with and regulate all aspects of the development of the germ cells...
  9. Gilleron J, Carette D, Carpentier F, Segretain D, Pointis G. Three-dimensional analysis of connexin 43 gap junction in the ex vivo rat seminiferous tubules: short-term effects of hormonal effectors. Microsc Res Tech. 2009;72:845-55 pubmed publisher
    ..few and indirect observations have been reported on the distribution of Cx43, the predominant Cx within the seminiferous tubules. In the present study, we developed an innovative method that allows visualization of the three- ..
  10. Reynard L, Cocquet J, Burgoyne P. The multi-copy mouse gene Sycp3-like Y-linked (Sly) encodes an abundant spermatid protein that interacts with a histone acetyltransferase and an acrosomal protein. Biol Reprod. 2009;81:250-7 pubmed publisher
    ..Together, these data suggest SLY1 may be involved in multiple processes during spermiogenesis, including the control of gene expression and the development or function of the acrosome...
  11. Shupe J, Cheng J, Puri P, Kostereva N, Walker W. Regulation of Sertoli-germ cell adhesion and sperm release by FSH and nonclassical testosterone signaling. Mol Endocrinol. 2011;25:238-52 pubmed publisher
    ..In contrast, FSH acts to limit testosterone-mediated ERK kinase activity and germ cell attachment...
  12. Pop O, Cotoi C, Pleşea I, Gherghiceanu M, Enache S, Mandache E, et al. Histological and ultrastructural analysis of the seminiferous tubule wall in ageing testis. Rom J Morphol Embryol. 2011;52:241-8 pubmed
    ..Our results showed that BM thickness is apparently decreasing with ageing whereas LP presents extremely variable degenerative changes, with a "mosaic", focal distribution and no tendency to advance with ageing...
  13. Abdou A, Hammam M, Farag A, Farouk S, Fawzy M. Immunohistochemical expression of cyclin A in testicular biopsies of fertile and infertile men: correlation with the morphometry of seminiferous tubules. Andrologia. 2011;43:57-64 pubmed publisher
    ..on cyclin A expression in various human spermatogenic disorders and its relationship to the morphology of seminiferous tubules are not well clarified...
  14. Ozen O, Akpolat N, Songur A, Kus I, Zararsiz I, Ozacmak V, et al. Effect of formaldehyde inhalation on Hsp70 in seminiferous tubules of rat testes: an immunohistochemical study. Toxicol Ind Health. 2005;21:249-54 pubmed
    ..Diameters of seminiferous tubules and serum testosterone levels in animals inhaling FA were significantly decreased...
  15. Kurahashi N, Kondo T, Omura M, Umemura T, Ma M, Kishi R. The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats. J Occup Health. 2005;47:437-44 pubmed
    ..Our study showed that inhaled DEHP increased plasma testosterone concentrations in prepubertal rats and suggested that their effects were more sensitive to inhalation of DEHP than oral dosing...
  16. Maeda Y, Shiratsuchi A, Namiki M, Nakanishi Y. Inhibition of sperm production in mice by annexin V microinjected into seminiferous tubules: possible etiology of phagocytic clearance of apoptotic spermatogenic cells and male infertility. Cell Death Differ. 2002;9:742-9 pubmed
    ..For this purpose, the PS-binding protein annexin V was microinjected into the seminiferous tubules of normal live mice, and their testes were examined...
  17. Kanatsu Shinohara M, Miki H, Inoue K, Ogonuki N, Toyokuni S, Ogura A, et al. Long-term culture of mouse male germline stem cells under serum-or feeder-free conditions. Biol Reprod. 2005;72:985-91 pubmed
    ..This culture system will provide a new opportunity for understanding the regulatory mechanism that governs spermatogonial stem cells...
  18. Segatelli T, Franca L, Pinheiro P, Alemida C, Martinez M, Martinez F. Spermatogenic cycle length and spermatogenic efficiency in the gerbil (Meriones unguiculatus). J Androl. 2004;25:872-80 pubmed
    ..Based on the volume occupied by seminiferous tubules in the testis and the tubular diameter, about 9 and 18 m of seminiferous tubules were found per testis and ..
  19. Stumpp T, Sasso Cerri E, Freymuller E, Miraglia S. Apoptosis and testicular alterations in albino rats treated with etoposide during the prepubertal phase. Anat Rec A Discov Mol Cell Evol Biol. 2004;279:611-22 pubmed
    ..Etoposide treatment during the prepubertal phase increases the frequency of apoptosis in the seminiferous epithelium, and causes serious harm to male fertility. 2004...
  20. Faure A, Pivot Pajot C, Kerjean A, Hazzouri M, Pelletier R, Peoc h M, et al. Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer. Mol Hum Reprod. 2003;9:757-63 pubmed
    ..A similar observation was made in the peritumoral seminiferous tubules of testicular tumour tissues, whenever they were lacking germinal cells, with carcinoma in situ (CIS) cells ..
  21. Altay B, Cetinkalp S, Doganavsargil B, Hekimgil M, Semerci B. Streptozotocin-induced diabetic effects on spermatogenesis with proliferative cell nuclear antigen immunostaining of adult rat testis. Fertil Steril. 2003;80 Suppl 2:828-31 pubmed
    ..To examine the histopathological effects of diabetes on spermatogenesis and to detect the proliferation of germ cells with proliferative cell nuclear antigen (PCNA)...
  22. Iguchi H, Watanabe M, Kamitani A, Nagai A, Hosoya O, Tsutsui K, et al. Localization of dynamin 2 in rat seminiferous tubules during the spermatogenic cycle. Acta Med Okayama. 2002;56:205-9 pubmed
    ..Dynamin 2 expression was observed using immunohistochemical method in the seminiferous tubules of all rats...
  23. Kita K, Watanabe T, Ohsaka K, Hayashi H, Kubota Y, Nagashima Y, et al. Production of functional spermatids from mouse germline stem cells in ectopically reconstituted seminiferous tubules. Biol Reprod. 2007;76:211-7 pubmed
    Testicular germ cell transplantation into the seminiferous tubules is at present the only way to induce spermatogenesis from a given source of spermatogonial stem cells...
  24. Behr R, Sackett S, Bochkis I, Le P, Kaestner K. Impaired male fertility and atrophy of seminiferous tubules caused by haploinsufficiency for Foxa3. Dev Biol. 2007;306:636-45 pubmed
    ..In summary, we have identified Foxa3 as a transcriptional regulator with a dominant phenotype in germ cell maintenance and suggest FOXA3 as a potential candidate gene for subfertility in man...
  25. Nagaosa K, Kishimoto A, Kizu R, Nakagawa A, Shiratsuchi A, Nakanishi Y. Perturbation of spermatogenesis by androgen antagonists directly injected into seminiferous tubules of live mice. Reproduction. 2007;133:21-7 pubmed
    ..We injected the androgen antagonists, flutamide and vinclozolin, directly into seminiferous tubules of live mice, which had been treated with busulfan for a temporal arrest of spermatogenesis, and the testes ..
  26. Gelain D, De Souza L, Bernard E. Extracellular purines from cells of seminiferous tubules. Mol Cell Biochem. 2003;245:1-9 pubmed
    ..communication mediated by purines were proposed; however, the cellular source(s) of these molecules in seminiferous tubules remains unknown...
  27. Nakai M, Van Cleeff J, Bahr J. Stages and duration of spermatogenesis in the domestic ferret (Mustela putorius furo). Tissue Cell. 2004;36:439-46 pubmed
    Classification of seminiferous tubules is the basis for understanding normal and abnormal spermatogenesis...
  28. Shi S, Rui M, Han W, Wang Y, Qiu X, Ding P, et al. CKLFSF2 is highly expressed in testis and can be secreted into the seminiferous tubules. Int J Biochem Cell Biol. 2005;37:1633-40 pubmed
    ..The data therefore strongly suggest that CKLFSF2 is a secreted protein that may be functionally relevant during spermatogenesis...
  29. Sasso Cerri E, Cerri P, Freymuller E, Miraglia S. Apoptosis during the seasonal spermatogenic cycle of Rana catesbeiana. J Anat. 2006;209:21-9 pubmed
    ..Thus, apoptosis may participate not only in the maintenance of spermatogenic homeostasis, but also in the cyclical control of the different spermatogenic processes according to seasonal changes of the testicular compartments as a whole...
  30. Sipahutar H, Sourdaine P, Moslemi S, Plainfosse B, Seralini G. Immunolocalization of aromatase in stallion Leydig cells and seminiferous tubules. J Histochem Cytochem. 2003;51:311-8 pubmed
    ..The present study in stallions indicates that in addition to Leydig cells, Sertoli cells also appear to participate in estrogen synthesis, and this could play a paracrine role in the regulation of spermatogenesis...
  31. Kotaja N, Kimmins S, Brancorsini S, Hentsch D, Vonesch J, Davidson I, et al. Preparation, isolation and characterization of stage-specific spermatogenic cells for cellular and molecular analysis. Nat Methods. 2004;1:249-54 pubmed
  32. Jeanes A, Wilhelm D, Wilson M, Bowles J, McClive P, Sinclair A, et al. Evaluation of candidate markers for the peritubular myoid cell lineage in the developing mouse testis. Reproduction. 2005;130:509-16 pubmed
    ..Although not strictly specific for PM cells, these markers are likely to be useful in studying the biology of early PM cells in the fetal testis...
  33. Masuda H, Fujihira S, Ueno H, Kagawa M, Katsuoka Y, Mori H. Ultrastructural study on cytotoxic effects of cyclosporine A in spermiogenesis in rats. Med Electron Microsc. 2003;36:183-91 pubmed
    ..A prominent change in the seminiferous tubules was an occurrence of numerous residual bodies containing one or more flagella...
  34. Chiarini Garcia H, Raymer A, Russell L. Non-random distribution of spermatogonia in rats: evidence of niches in the seminiferous tubules. Reproduction. 2003;126:669-80 pubmed
    ..the results of this study strongly indicate that the most primitive type A spermatogonia (A(s), A(paired) and A(al)) in rats are present in niches located in those areas of the seminiferous tubules that border the interstitial tissue.
  35. Kanatsu Shinohara M, Toyokuni S, Shinohara T. Transgenic mice produced by retroviral transduction of male germ line stem cells in vivo. Biol Reprod. 2004;71:1202-7 pubmed
    ..Microinjection of retrovirus into immature seminiferous tubules resulted in the direct transduction of spermatogonial stem cells in situ, and the animals produced ..
  36. Romano F, Tripiciano A, Muciaccia B, De Cesaris P, Ziparo E, Palombi F, et al. The contractile phenotype of peritubular smooth muscle cells is locally controlled: possible implications in male fertility. Contraception. 2005;72:294-7 pubmed
    ..activity of peritubular tissue is responsible for the propulsion of spermatozoa along the lumen of seminiferous tubules toward the hilum of the testis...
  37. Gassei K, Schlatt S, Ehmcke J. De novo morphogenesis of seminiferous tubules from dissociated immature rat testicular cells in xenografts. J Androl. 2006;27:611-8 pubmed
    ..The grafts were vascularized and contained elongated seminiferous tubules. Histologic analysis revealed the presence of a basement membrane, a histologically normal interstitium ..
  38. Khaki A, Tubbs R, Shoja M, Rad J, Khaki A, Farahani R, et al. The effects of an electromagnetic field on the boundary tissue of the seminiferous tubules of the rat: A light and transmission electron microscope study. Folia Morphol (Warsz). 2006;65:188-94 pubmed
    ..of EMF in order to observe recovery, if any, from the changes induced by EMF on the boundary tissue of the seminiferous tubules. The materials were processed and observed under a light and a transmission electron microscope...
  39. Brehm R, Marks A, Rey R, Kliesch S, Bergmann M, Steger K. Altered expression of connexins 26 and 43 in Sertoli cells in seminiferous tubules infiltrated with carcinoma-in-situ or seminoma. J Pathol. 2002;197:647-53 pubmed
  40. Wang F, Zhang Q, Cao J, Huang Q, Zhu X. The microtubule plus end-binding protein EB1 is involved in Sertoli cell plasticity in testicular seminiferous tubules. Exp Cell Res. 2008;314:213-26 pubmed
    ..Seminiferous tubule circularity and germ cell number were also reduced. These data indicate a requirement of proper microtubule arrays for Sertoli cell plasticity and function in testis...
  41. Wong P. Do seminiferous tubules secrete a fluid rich in KHCO3?. J Physiol. 2002;542:335 pubmed
  42. Ishii M, Tachiwana T, Hoshino A, Tsunekawa N, Hiramatsu R, Matoba S, et al. Potency of testicular somatic environment to support spermatogenesis in XX/Sry transgenic male mice. Development. 2007;134:449-54 pubmed
    ..Microarray analysis of seminiferous tubules isolated from XX/Sry testes confirmed the missing expression of several Y-linked genes and the alterations ..
  43. Takubo K, Hirao A, Ohmura M, Azuma M, Arai F, Nagamatsu G, et al. Premeiotic germ cell defect in seminiferous tubules of Atm-null testis. Biochem Biophys Res Commun. 2006;351:993-8 pubmed
    ..It has been shown that ataxia telangiectasia-mutated (ATM) is required for meiotic division of the seminiferous tubules. Here, we show that, in addition to its role in meiosis, ATM has a pivotal role in premeiotic germ cell ..
  44. Nair R, Shaha C. Diethylstilbestrol induces rat spermatogenic cell apoptosis in vivo through increased expression of spermatogenic cell Fas/FasL system. J Biol Chem. 2003;278:6470-81 pubmed
  45. Kanatsu Shinohara M, Ogonuki N, Inoue K, Miki H, Ogura A, Toyokuni S, et al. Long-term proliferation in culture and germline transmission of mouse male germline stem cells. Biol Reprod. 2003;69:612-6 pubmed
    ..and restored fertility to congenitally infertile recipient mice following transplantation into seminiferous tubules. Long-term spermatogonial stem cell culture will be useful for studying spermatogenesis mechanism and has ..
  46. Brinster R. Germline stem cell transplantation and transgenesis. Science. 2002;296:2174-6 pubmed
    ..The technique also is being used to examine spermatogenic defects, correct male infertility, and generate transgenic animals...
  47. Fisher J, MacPherson S, Marchetti N, Sharpe R. Human 'testicular dysgenesis syndrome': a possible model using in-utero exposure of the rat to dibutyl phthalate. Hum Reprod. 2003;18:1383-94 pubmed
    ..The disorders comprising human 'testicular dysgenesis syndrome' (TDS) may be increasing in incidence. TDS originates in fetal life but the mechanisms are not known, and discerning them requires an animal model...
  48. Morales E, Horn R, Pastor L, Santamaria L, Pallares J, Zuasti A, et al. Involution of seminiferous tubules in aged hamsters: an ultrastructural, immunohistochemical and quantitative morphological study. Histol Histopathol. 2004;19:445-55 pubmed publisher
    In this study, we examined the age-related changes on morphometric parameters and ultrastructure of seminiferous tubules, and on the expression of extracellular matrix proteins in lamina propria of Syrian hamsters...
  49. Favorito L, Hidalgo A, Pazos H, Costa W, Sampaio F. Stereological and morphometric analysis of collagen and seminiferous tubules in testes of patients with cryptorchidism submitted or not to treatment with human chorionic gonadotrophin. Int Braz J Urol. 2005;31:562-6; discussion 567-8 pubmed
    Quantify the distribution of collagen and analyze the seminiferous tubules diameter in the testis of patients with cryptorchidism, to verify if the previous use of human chorionic gonadotrophin (hCG) affects these structures.
  50. Sasso Cerri E, Miraglia S. In situ demonstration of both TUNEL-labeled germ cell and Sertoli cell in the cimetidine-treated rats. Histol Histopathol. 2002;17:411-7 pubmed publisher
    ..Besides germ cells, TUNEL-positive Sertoli cells were also found in the injured seminiferous tubules. Thus, a relationship between dying germ cells and Sertoli cell damage and/or death must be considered in ..
  51. Riccioli A, Starace D, Galli R, Fuso A, Scarpa S, Palombi F, et al. Sertoli cells initiate testicular innate immune responses through TLR activation. J Immunol. 2006;177:7122-30 pubmed
    ..Collectively, this study demonstrates the novel ability of Sertoli cells to potentially respond to a wide variety of bacteria through TLR stimulation...
  52. Fortoul T, Bizarro Nevares P, Acevedo Nava S, Piñón Zarate G, Rodriguez Lara V, Colin Barenque L, et al. Ultrastructural findings in murine seminiferous tubules as a consequence of subchronic vanadium pentoxide inhalation. Reprod Toxicol. 2007;23:588-92 pubmed
    ..The relevance of this report concerns the impact that metal air pollution could have on male fertility in dense cities with vehicular traffic problems...
  53. Takahashi M, Shibutani M, Nakahigashi J, Sakaguchi N, Inoue K, Morikawa T, et al. Limited lactational transfer of acrylamide to rat offspring on maternal oral administration during the gestation and lactation periods. Arch Toxicol. 2009;83:785-93 pubmed publisher
  54. Morais D, de Paula T, Barros M, Balarini M, de Freitas M, da Matta S. Stages and duration of the seminiferous epithelium cycle in the bat Sturnira lilium. J Anat. 2013;222:372-9 pubmed publisher
    ..The presence of primary spermatocytes at zygotene in stage 1 of the cycle is probably due to the longer duration of this stage...