Gestational and lactational exposure of male mice to diethylstilbestrol causes long-term effects on the testis, sperm fertilizing ability in vitro, and testicular gene expression.
The objective of the study was to determine the long-term effects of gestational and lactational exposure to diethylstilbestrol (DES; 0, 0.1, 1, and 10 microg/kg maternal body weight) on mouse testicular growth, epididymal sperm count, in vitro fertilizing ability, and testicular gene expression using cDNA microarrays and real-time PCR in mice on postnatal day (PND) 21, 105, and 315. In the high dose group there was a persistent decrease in the number of Sertoli cells, and sperm count was decreased on PND315 (P < 0.05). Sperm motion was unaffected; however, the in vitro fertilizing ability of epididymal sperm was decreased in the high dose group on both PND105 (P < 0.001) and PND315 (P < 0.05). Early and latent alterations in the expression of genes involved in estrogen signaling (estrogen receptor alpha), steroidogenesis (steroidogenic factor 1, 17alpha-hydroxylase/C17,20-lyase, P450 side chain cleavage, steroidogenic acute regulatory protein, and scavenger receptor class B1), lysosomal function (LGP85 and prosaposin), and regulation of testicular development (testicular receptor 2, inhibin/activin beta C, and Hoxa10) were confirmed by real-time PCR. The results demonstrate that early exposure to DES causes long-term adverse effects on testicular development and sperm function, and these effects are associated with changes in testicular gene expression, even long after the cessation of DES exposure.
Fielden
Mark R
MR
Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center, Institute for Environmental Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Halgren
Robert G
RG
Fong
Cora J
CJ
Staub
Christophe
C
Johnson
Larry
L
Chou
Karen
K
Zacharewski
Tim R
TR
D000818:Animals; D004054:Diethylstilbestrol / Q000633:toxicity*; D005260:Female; D005307:Fertilization in Vitro; D005333:Fetus / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D007774:Lactation; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013094:Spermatozoa / Q000187:drug effects*; D013737:Testis / Q000187:drug effects* / Q000378:metabolism
D004054:Diethylstilbestrol