{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:33:40Z","timestamp":1791326020712,"version":"4.3.1"},"reference-count":43,"publisher":"The Company of Biologists","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,1,15]]},"abstract":"<jats:p>The vertebrate nuclear hormone receptor steroidogenic factor 1 (SF1; NR5A1)controls reproductive development and regulates the transcription of steroid-modifying cytochrome P450 genes. We find that the SF1-related Drosophila nuclear hormone receptor HR39 is also essential for sexual development. In Hr39 mutant females, the sperm-storing spermathecae and glandular parovaria are absent or defective, causing sterility. Our results indicate that spermathecae and parovaria secrete reproductive tract proteins required for sperm maturation and function, like the mammalian epididymis and female reproductive tract. Hr39 controls the expression of specific cytochrome P450 genes and is required in females both to activate spermathecal secretion and repress male-specific courtship genes such as takeout. Thus, a pathway that, in vertebrates, controls sex-specific steroid hormone production, also mediates reproductive functions in an invertebrate. Our findings suggest that Drosophila can be used to model more aspects of mammalian reproductive biology than previously believed.<\/jats:p>","DOI":"10.1242\/dev.015156","type":"journal-article","created":{"date-parts":[[2007,12,13]],"date-time":"2007-12-13T01:44:57Z","timestamp":1197510297000},"page":"311-321","source":"Crossref","is-referenced-by-count":109,"title":["The<i>Sf1<\/i>-related nuclear hormone receptor<i>Hr39<\/i>regulates<i>Drosophila<\/i>female reproductive tract development and function"],"prefix":"10.1242","volume":"135","author":[{"given":"Anna K.","family":"Allen","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan C.","family":"Spradling","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Embryology, Carnegie Institution, 3520 San Martin Drive, Baltimore, MD 21218, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2021042605501483900_REF1","doi-asserted-by":"crossref","unstructured":"Anderson, R. C. (1945). A study of the factors affecting fertility of lozenge females of Drosophila melanogaster. Genetics30,280-296.","DOI":"10.1093\/genetics\/30.3.280"},{"key":"2021042605501483900_REF2","doi-asserted-by":"crossref","unstructured":"Arbeitman, M. N., Fleming, A. A., Siegal, M. L., Null, B. H. and Baker, B. S. (2004). A genomic analysis of Drosophila somatic sexual differentiation and its regulation. Development131,2007-2021.","DOI":"10.1242\/dev.01077"},{"key":"2021042605501483900_REF3","doi-asserted-by":"crossref","unstructured":"Barnett, T., Pachl, C., Gergen, J. P. and Wensink, P. C.(1980). The isolation and characterization of Drosophila yolk protein genes. Cell21,729-738.","DOI":"10.1016\/0092-8674(80)90436-5"},{"key":"2021042605501483900_REF4","doi-asserted-by":"crossref","unstructured":"Bloch Qazi, M. C., Heifetz, Y. and Wolfner, M. F.(2003). The developments between gametogenesis and fertilization:ovulation and female sperm storage in Drosophila melanogaster. Dev. 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Cambridge: Cambridge University Press.","DOI":"10.1017\/CBO9780511545115.005"},{"key":"2021042605501483900_REF11","doi-asserted-by":"crossref","unstructured":"Cox, R. T. and Spradling, A. C. (2003). A Balbiani body and the fusome mediate mitochondrial inheritance during Drosophila oogenesis. Development130,1579-1590.","DOI":"10.1242\/dev.00365"},{"key":"2021042605501483900_REF12","doi-asserted-by":"crossref","unstructured":"Dauwalder, B., Tsujimoto, S., Moss, J. and Mattox, W.(2002). The Drosophila takeout gene is regulated by the somatic sex-determination pathway and affects male courtship behavior. Genes Dev.16,2879-2892.","DOI":"10.1101\/gad.1010302"},{"key":"2021042605501483900_REF13","unstructured":"De Loof, A., Baggerman, G., Breuer, M., Claeys, I., Cerstiaens,A., Clynen, E., Janssen, T., Schoofs, L. and Vanden Broeck, J.(1998). Insects do not have sex hormones: a myth?Arch. Insect Biochem. Physiol.47,129-138."},{"key":"2021042605501483900_REF14","doi-asserted-by":"crossref","unstructured":"Drevet, J. R. (2006). The antioxidant glutathione peroxidase family and spermatozoa: a complex story. Gen. Comp. Endocrinol.111,245-260.","DOI":"10.1016\/j.mce.2005.12.027"},{"key":"2021042605501483900_REF15","doi-asserted-by":"crossref","unstructured":"Fayard, E., Auwerx, J. and Schoonjans, K.(2004). LRH-1: an orphan nuclear receptor involved in development, metabolism and steroidogenesis. Trends Cell Biol.14,250-260.","DOI":"10.1016\/j.tcb.2004.03.008"},{"key":"2021042605501483900_REF16","unstructured":"Filosi, M. and Perotti, M. E. (1975). Fine structure of the spermathecae of Drosophila melanogaster. J. Submicrosc. Cytol.7,259-270."},{"key":"2021042605501483900_REF17","doi-asserted-by":"crossref","unstructured":"Frenette, G., Thabet, M. and Sullivan, R.(2006). Polyol pathway in human epididymis and semen. J. 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A. and Thummel, C. S. (1997). Mutations in the DHR39 orphan receptor gene have no effect on viability. Drosoph. Inf. Serv.80,35-37."},{"key":"2021042605501483900_REF22","doi-asserted-by":"crossref","unstructured":"Jelinsky, S. A., Turner, T. T., Bang, H. J., Finger, J. N.,Solarz, M. K., Wilson, E., Brown, E. L., Kopf, G. S. and Johnston, D. S.(2007). The rat epididymal transcriptome: comparison of segmental gene expression in the rat and mouse epididymides. Biol. Reprod.76,561-570.","DOI":"10.1095\/biolreprod.106.057323"},{"key":"2021042605501483900_REF23","doi-asserted-by":"crossref","unstructured":"Johnston, D. S., Turner, T. T., Finger, J. N., Owtscharuk, T. L., Kopf, G. S. and Jelinsky, S. A. (2007). Identification of epididymis-specific transcripts in the mouse and rat by transcriptional profiling. Asian J. 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