Toxicogenomic effects of neonatal exposure to diethylstilbestrol on mouse testicular gene expression in the long term: A study using cDNA microarray analysis

• Published in: Molecular reproduction and development 2002-09, Vol.63 (1), p.17-23
• Main Authors: Adachi, Tetsuya, Komiyama, Masatoshi, Ono, Yushin, Koh, Kyu-Bom, Sakurai, Kenichi, Shibayama, Takako, Kato, Masaki, Yoshikawa, Tsutomu, Seki, Naohiko, Iguchi, Taisen, Mori, Chisato
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; cDNA microarray; diethylstilbestrol; Diethylstilbestrol - pharmacology; Female; Fundamental and applied biological sciences. Psychology; Gene expression; Gene Expression Profiling; Gene Expression Regulation - drug effects; Humans; Infertility, Male - chemically induced; Infertility, Male - genetics; Male; Mice; Mice, Inbred ICR; Molecular and cellular biology; Molecular genetics; neonatal treatment; Oligonucleotide Array Sequence Analysis; Pregnancy; Prenatal Exposure Delayed Effects; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Spermatogenesis - drug effects; Subtraction Technique; testis; Testis - metabolism; Testis - ultrastructure; toxicogenomics
• ISSN: 1040-452X; 1098-2795
• DOI: 10.1002/mrd.10178

We examined the effect of neonatal exposure to diethylstilbestrol (DES) on mouse testicular gene expression, using in‐house mouse fetus (day 14.5) cDNA microarrays. Newborn male ICR mice were exposed to DES (50 μg/mouse/day) from neonatal day 1 to 5. Differential expression was detected in 14 genes in 4‐week‐old (day 28) mouse testes by cDNA microarray analysis; 11 genes (AI035263, AU080565, AU080361, AU080678, AI131681, AU080631, AA986882, AI037066, AA986537, AI156816, and AI596237) were up‐regulated and three genes (AI131656, AI118968, and AI117606) were down‐regulated in DES‐treated mouse testes. Higher expression levels of the former eight genes, out of the up‐regulated genes picked‐up by the microarray, were also confirmed by reverse transcription and real‐time polymerase chain reaction (real‐time RT‐PCR) analysis. However, the differential expression of other genes could not be confirmed. Real‐time RT‐PCR analysis also revealed that expression levels of the eight genes were still higher in DES‐treated testes at 8 and 12 weeks of age. Our results suggest that cDNA microarray analysis is a useful method by which a large number of gene expressions are simultaneously detected and changes in gene expression are screened. In addition, our results suggest that these genes, whose expressions are changed in the testes of adult mice by fetal or neonatal exposure to exogenous chemicals, might be candidates for predictive biological markers. Mol. Reprod. Dev. 63: 17–23, 2002. © 2002 Wiley‐Liss, Inc.