Effects of maternal exposure to low doses of DES on testicular steroidogenesis and spermatogenesis in male rat offspring.
Our previous studies have demonstrated that prenatally administered diethylstilbestrol (DES) impairs testicular endocrine function in male offspring. The present study examined whether maternal DES treatment influences testicular steroidogenesis and spermatogenesis. DES was injected subcutaneously at 0.5 or 1.5 microg/kg/day (DES 0.5 and 1.5 groups, respectively) into pregnant SD rats on days 7-21 of gestation. Male offspring in the DES 0.5 and 1.5 groups were autopsied at 1, 3, 6 and 15 weeks after birth. At 1 week, DES treatment did not lead to a change in the volume of P450scc-positive cells (Leydig cells), suggesting that DES has no inhibitory effect on the development of Leydig cells. DES administration disrupted luteinizing hormone receptor (LHr) expression and exerted inhibitory effects on signal transduction from LHr to steroidogenic acute regulatory protein (StAR) in testicular steroidogenesis (P<0.05), although there were no changes in the mRNA expression levels of steroidogenic enzymes, such as P450scc, 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and P450(17 alpha), which may have caused a decrease in the plasma testosterone level. DES treatment did not disrupt the cycle of spermatogenesis but did upregulate the expression levels of androgen receptor (AR) mRNA in both DES groups at 15 weeks (P<0.05). These results indicate that maternal DES treatment disrupts steroidogenesis but induces a high level of AR mRNA expression to counteract the low levels of testosterone during spermatogenesis.
Kobayashi
Tetsuo
T
Department of Anatomy II, School of Veterinary Medicine, Azabu University, Kanagawa, Japan.
Shirai
Mitsuyuki
M
Sakaue
Motoharu
M
Murakami
Masaru
M
Ochiai
Hideharu
H
Arishima
Kazuyoshi
K
Yamamoto
Masako
M
D000375:Aging; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004054:Diethylstilbestrol / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012671:Seminiferous Tubules / Q000187:drug effects / Q000502:physiology; D013091:Spermatogenesis / Q000187:drug effects*; D013735:Testicular Hormones / Q000096:biosynthesis* / Q000097:blood; D013737:Testis / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D013735:Testicular Hormones; D004054:Diethylstilbestrol