The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
Impairment of spermatogenesis in mice lacking a functional aromatase (cyp 19) gene
Open accessAbstract
It is well established that spermatogenesis is controlled by gonadotrophins and testosterone. However, a role for estrogens in male reproduction recently was suggested in adult mice deficient in estrogen receptor α. These mice became infertile primarily because of an interruption of fluid reabsorption by the efferent ductules of the epididymis, thus leading to a disruption of the seminiferous epithelium [Hess, R. A., Bunick, D., Lee, K. H., Bahr, J., Taylor, J. A., Korach, K. S., and Lubahn, D. B. (1997)Nature (London)390, 509–512]. Despite the demonstration of the aromatase enzyme, which converts androgens to estrogens, and estrogen receptors within the rodent seminiferous epithelium, the role of aromatase and estrogen in germ cell development is unknown. We have investigated spermatogenesis in mice that lack aromatase because of the targeted disruption of the cyp19 gene (ArKO). Male mice deficient in aromatase were initially fertile but developed progressive infertility, until their ability to sire pups was severely impaired. The mice deficient in aromatase developed disruptions to spermatogenesis between 4.5 months and 1 year, despite no decreases in gonadotrophins or androgens. Spermatogenesis primarily was arrested at early spermiogenic stages, as characterized by an increase in apoptosis and the appearance of multinucleated cells, and there was a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells. In addition, Leydig cell hyperplasia/hypertrophy was evident, presumably as a consequence of increased circulating luteinizing hormone. Our findings indicate that local expression of aromatase is essential for spermatogenesis and provide evidence for a direct action of estrogen on male germ cell development and thus fertility.
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Citations
Cites
Effect of testosterone and estradiol in a man with aromatase deficiency
Carani, C., Qin, K., Simoni, M., Faustini-Fustini, M., Serpente, S., Boyd, J., Korach, K. S., & Simpson, E. R. (1997) · New England Journal of Medicine · doi:10.1056/nejm199707103370204 · Cited by 1,151
Self-citationFisher, C. R., Graves, K. H., Parlow, A. F., & Simpson, E. R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.12.6965 · Cited by 867
Self-citationCellular localization of rat testicular aromatase activity during development
TSAI-MORRIS, C.-H., AQUILANO, D. R., & DUFAU, M. L. (1985) · Endocrinology · doi:10.1210/endo-116-1-38 · Cited by 152
Cited by
Sources of estrogen and their importance
Simpson, E. R. (2003) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(03)00360-1 · Cited by 936
Self-citationSimpson, E. R., Clyne, C., Rubin, G., Boon, W. C., Robertson, K., Britt, K., Speed, C., & Jones, M. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.081601.142703 · Cited by 773
Self-citationAromatase-deficient (ArKO) mice have a phenotype of increased adiposity
Jones, M. E. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., Yao, S., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.23.12735 · Cited by 729
Self-citationSex chromosomes and brain gender
Arnold, A. P. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1494 · Cited by 368
The role of local estrogen Biosynthesis in males and females
Simpson, E., Rubin, G., Clyne, C., Robertson, K., O’Donnell, L., Jones, M., & Davis, S. (2000) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(00)00254-x · Cited by 249
Self-citationOf mice and men: the evolving phenotype of aromatase deficiency
Jones, M. E. E., Chin Boon, W., Proietto, J., & Simpson, E. R. (2006) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2006.01.004 · Cited by 193
Self-citationAquila, S., Sisci, D., Gentile, M., Middea, E., Catalano, S., Carpino, A., Rago, V., & Andò, S. (2004) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2003-031681 · Cited by 184
Aromatase-deficient (ArKO) mice accumulate excess adipose tissue
Jones, M. E. E., Thorburn, A. W., Britt, K. L., Hewitt, K. N., Misso, M. L., Wreford, N. G., Proietto, J., Oz, O. K., Leury, B. J., Robertson, K. M., et al. (2001) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(01)00136-4 · Cited by 141
Self-citationStolzenberg, D. S., & Rissman, E. F. (2011) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2011.02112.x · Cited by 128
Effect of estrogen deficiency in the male: the ArKO mouse model
Murata, Y., Robertson, K. M., Jones, M. E. E., & Simpson, E. R. (2002) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(02)00090-4 · Cited by 111
Self-citationVitamin D metabolism, sex hormones, and male reproductive function
Blomberg Jensen, M. (2012) · Reproduction · doi:10.1530/rep-12-0064 · Cited by 103
Genetic or enzymatic disruption of aromatase inhibits the growth of ectopic uterine tissue
Fang, Z., Yang, S., Gurates, B., Tamura, M., Simpson, E., Evans, D., & Bulun, S. E. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.7.8683 · Cited by 91
Self-citationHepatic Glucose Intolerance Precedes Hepatic Steatosis in the Male Aromatase Knockout (ArKO) Mouse
Van Sinderen, M. L., Steinberg, G. R., Jørgensen, S. B., To, S. Q., Knower, K. C., Clyne, C. D., Honeyman, J., Chow, J. D., Herridge, K. A., Jones, M. E. E., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087230 · Cited by 26
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Metadata
- Authors
- Robertson, K. M., O’Donnell, L., Jones, M. E. E., Meachem, S. J., Boon, W. C., Fisher, C. R., Graves, K. H., McLachlan, R. I., & Simpson, E. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1999-07-06
- Volume
- 96
- Issue
- 14
- Pages
- 7986-7991
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2070282026
- Cited by
- 592
- References
- 3
- FWCI
- 36.00
- Type
- journal article
- Language
- en
- Open access
- green
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