Sex-dependent aromatase activity in rat offspring after pre- and postnatal exposure to triphenyltin chloride.
Triphenyltin (TPT) is an organotin compound (OTC) previously widely used as an antifouling agent in paints applied in the marine environment, a fungicide, and as an agricultural pesticide. In female aquatic invertebrates, certain OTCs induce the so-called imposex, an abnormal induction of male sex characteristics. OTC-induced environmental endocrine disruption also occurs in fish and mammals and a number of in vivo and in vitro studies have argued that OTCs may act through inhibition of the aromatase enzyme. In vivo studies supporting the aromatase inhibition hypothesis in mammals are lacking. Recently, the causal relationship between inhibition of aromatase and imposex was questioned, suggesting aromatase independent mechanisms of action for this phenomenon. We conducted a comprehensive investigation to identify the most sensitive window of exposure to TPTCl and to examine the effects of pre- and postnatal exposure on postnatal development in rats. The results on brain and gonadal aromatase activity obtained from offspring of dams exposed to 2 mg TPTCl/kg bw are reported here. Female and male offspring rats were exposed to 2 mg TPTCl/kg bw/d in utero from gestation day 6 through lactation until weaning on PND 21, or from gestation day 6 until termination at adulthood. Male offspring were sacrificed from PND 58 and female offspring at first estrus after PND 58. Pre- and postnatal TPT exposure clearly affected brain and gonadal aromatase activity in a sex-dependent fashion. While brain aromatase activity was significantly increased on PND 21 and at adulthood in female offspring, male offspring exhibited a significant decrease in brain aromatase activity only at adulthood. Ovarian aromatase activity was unaffected at both time points investigated. In contrast, testicular aromatase activity was significantly increased in males on PND 21 and significantly decreased at adulthood independent from the duration of treatment. The results of the present study confirm our previously reported observations regarding sex-dependent differences in sexual development after TPT exposure with the male rat being more susceptible to disturbances through this endocrine active compound than the female. We conclude that TPT administered during the particularly vulnerable period of development can affect aromatase activity in rats.
Hobler
Carolin
C
Inst. of Clinical Pharmacology and Toxicology, Charité University Medical School, Campus Benjamin Franklin, 14195 Berlin, Germany.
Andrade
Anderson J M
AJ
Grande
Simone Wichert
SW
Gericke
Christine
C
Talsness
Chris E
CE
Appel
Klaus E
KE
Chahoud
Ibrahim
I
Grote
Konstanze
K
D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D052244:Endocrine Disruptors / Q000008:administration & dosage / Q000633:toxicity*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D006066:Gonads / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009947:Organotin Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D012727:Sex Characteristics
D052244:Endocrine Disruptors; D009947:Organotin Compounds; C030665:triphenyltin; D001141:Aromatase