Sox8 is a Critical Regulator of Adult Sertoli Cell Function and Male Fertility

Overview

Journal Dev Biol

Publisher Elsevier

Specialties Biology
Reproductive Medicine

Date 2008 Mar 18

PMID 18342849

Citations 53

Authors

Moira K OBryan

Shuji Takada

Claire L Kennedy

Greg Scott

Shun-ichi Harada

Manas K Ray

Qunsheng Dai

Dagmar Wilhelm

David M de Kretser

E Mitch Eddy

Peter Koopman

Yuji Mishina

Affiliations

Soon will be listed here.

Abstract

Sox8 encodes a high-mobility group transcription factor that is widely expressed during development. Sox8, -9 and -10 form group E of the Sox gene family which has been implicated in several human developmental disorders. In contrast to other SoxE genes, the role of Sox8 is unclear and Sox8 mouse mutants reportedly showed only idiopathic weight loss and reduced bone density. The careful analysis of our Sox8 null mice, however, revealed a progressive male infertility phenotype. Sox8 null males only sporadically produced litters of reduced size at young ages. We have shown that SOX8 protein is a product of adult Sertoli cells and its elimination results in an age-dependent deregulation of spermatogenesis, characterized by sloughing of spermatocytes and round spermatids, spermiation failure and a progressive disorganization of the spermatogenic cycle, which resulted in the inappropriate placement and juxtaposition of germ cell types within the epithelium. Those sperm that did enter the epididymides displayed abnormal motility. These data show that SOX8 is a critical regulator of adult Sertoli cell function and is required for both its cytoarchitectural and paracrine interactions with germ cells.

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References

Pingault V, Guiochon-Mantel A, Bondurand N, Faure C, Lacroix C, Lyonnet S . Peripheral neuropathy with hypomyelination, chronic intestinal pseudo-obstruction and deafness: a developmental "neural crest syndrome" related to a SOX10 mutation. Ann Neurol. 2000; 48(4):671-6. View

Pfeiffer D, Vogl A . Evidence that vinculin is co-distributed with actin bundles in ectoplasmic ("junctional") specializations of mammalian Sertoli cells. Anat Rec. 1991; 231(1):89-100. DOI: 10.1002/ar.1092310110. View

Schepers G, Bullejos M, Hosking B, Koopman P . Cloning and characterisation of the Sry-related transcription factor gene Sox8. Nucleic Acids Res. 2000; 28(6):1473-80. PMC: 111037. DOI: 10.1093/nar/28.6.1473. View

Pontiggia A, RIMINI R, Harley V, Goodfellow P, Lovell-Badge R, Bianchi M . Sex-reversing mutations affect the architecture of SRY-DNA complexes. EMBO J. 1994; 13(24):6115-24. PMC: 395591. DOI: 10.1002/j.1460-2075.1994.tb06958.x. View

Kramer J, Erickson R . Developmental program of PGK-1 and PGK-2 isozymes in spermatogenic cells of the mouse: specific activities and rates of synthesis. Dev Biol. 1981; 87(1):37-45. DOI: 10.1016/0012-1606(81)90058-0. View

Schepers G, Teasdale R, Koopman P . Twenty pairs of sox: extent, homology, and nomenclature of the mouse and human sox transcription factor gene families. Dev Cell. 2002; 3(2):167-70. DOI: 10.1016/s1534-5807(02)00223-x. View

Robb G, Amann R, Killian G . Daily sperm production and epididymal sperm reserves of pubertal and adult rats. J Reprod Fertil. 1978; 54(1):103-7. DOI: 10.1530/jrf.0.0540103. View

Falender A, Freiman R, Geles K, Lo K, Hwang K, Lamb D . Maintenance of spermatogenesis requires TAF4b, a gonad-specific subunit of TFIID. Genes Dev. 2005; 19(7):794-803. PMC: 1074317. DOI: 10.1101/gad.1290105. View

Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J . Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9. Cell. 1994; 79(6):1111-20. DOI: 10.1016/0092-8674(94)90041-8. View

10.

Sock E, Schmidt K, Bosl M, Wegner M . Idiopathic weight reduction in mice deficient in the high-mobility-group transcription factor Sox8. Mol Cell Biol. 2001; 21(20):6951-9. PMC: 99871. DOI: 10.1128/MCB.21.20.6951-6959.2001. View

11.

Hong C, Saint-Jeannet J . Sox proteins and neural crest development. Semin Cell Dev Biol. 2005; 16(6):694-703. DOI: 10.1016/j.semcdb.2005.06.005. View

12.

Young N, Hahn C, Poh A, Dong C, Wilhelm D, Olsson J . Effect of disrupted SOX18 transcription factor function on tumor growth, vascularization, and endothelial development. J Natl Cancer Inst. 2006; 98(15):1060-7. DOI: 10.1093/jnci/djj299. View

13.

Kennedy C, OConnor A, Sanchez-Partida L, Holland M, Goodnow C, de Kretser D . A repository of ENU mutant mouse lines and their potential for male fertility research. Mol Hum Reprod. 2006; 11(12):871-80. DOI: 10.1093/molehr/gah251. View

14.

Schepers G, Wilson M, Wilhelm D, Koopman P . SOX8 is expressed during testis differentiation in mice and synergizes with SF1 to activate the Amh promoter in vitro. J Biol Chem. 2003; 278(30):28101-8. DOI: 10.1074/jbc.M304067200. View

15.

Lee N, Cheng C . Ectoplasmic specialization, a testis-specific cell-cell actin-based adherens junction type: is this a potential target for male contraceptive development?. Hum Reprod Update. 2004; 10(4):349-69. DOI: 10.1093/humupd/dmh026. View

16.

Kos L, Pavan W . Sox10 mutation disrupts neural crest development in Dom Hirschsprung mouse model. Nat Genet. 1998; 18(1):60-4. DOI: 10.1038/ng0198-60. View

17.

Slott V, Suarez J, Poss P, Linder R, Strader L, Perreault S . Optimization of the Hamilton-Thorn computerized sperm motility analysis system for use with rat spermatozoa in toxicological studies. Fundam Appl Toxicol. 1993; 21(3):298-307. DOI: 10.1006/faat.1993.1102. View

18.

Beardsley A, ODonnell L . Characterization of normal spermiation and spermiation failure induced by hormone suppression in adult rats. Biol Reprod. 2003; 68(4):1299-307. DOI: 10.1095/biolreprod.102.009811. View

19.

Miki K, Willis W, Brown P, Goulding E, Fulcher K, Eddy E . Targeted disruption of the Akap4 gene causes defects in sperm flagellum and motility. Dev Biol. 2002; 248(2):331-42. DOI: 10.1006/dbio.2002.0728. View

20.

OBryan M, Schlatt S, Phillips D, de Kretser D, Hedger M . Bacterial lipopolysaccharide-induced inflammation compromises testicular function at multiple levels in vivo. Endocrinology. 1999; 141(1):238-46. DOI: 10.1210/endo.141.1.7240. View