Impact of dietary exposure to methoxychlor, genistein, or diisononyl phthalate during the perinatal period on the development of the rat endocrine/reproductive systems in later life.
To evaluate the impact of dietary exposure to endocrine disrupting chemicals (EDCs) during the sensitive period of brain sexual differentiation, maternal Sprague-Dawley rats were fed three representative chemicals, methoxychlor (MXC; 24, 240, and 1200 ppm), genistein (GEN; 20, 200, and 1000 ppm), or diisononyl phthalate (DINP; 400, 4000, and 20,000 ppm), from gestational day 15 to postnatal day 10. Soy-free diet was used as a basal diet to eliminate possible estrogenic effects from the standard diet. Offspring were examined in terms of anogenital distances, prepubertal organ weights, onset of puberty, estrous cyclicity, and organ weights and histopathology of endocrine organs at adult stage (week 11) as well as the volumes of sexually dimorphic nucleus of preoptic area (SDN-POA). All chemicals caused signs of maternal toxicity at high doses. MXC, at 1200 ppm, facilitated and delayed the onset of puberty in females and males, respectively, females also showing endocrine disrupting effects thereafter, such as irregular estrous cyclicity and histopathological alterations in the reproductive tract and anterior pituitary. GEN, at all doses, reduced body weight (BW) at week 11, but did not affect endocrine parameters. Treatment with DINP at 20,000 ppm resulted in degeneration of meiotic spermatocytes and Sertoli cells in the testis and decrease of corpora lutea in the ovary at week 11, although changes remained minimal or slight. The SDN-POA volume remained unchanged with all three chemicals. The results demonstrated that perinatal dietary exposure to EDCs for a limited period causes endocrine disruption in offspring only at high doses.
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
Naoya
N
Masutomi
Makoto
M
Shibutani
Hironori
H
Takagi
Chikako
C
Uneyama
Noriyuki
N
Takahashi
Masao
M
Hirose
D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004703:Endocrine System / Q000187:drug effects* / Q000254:growth & development; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D019833:Genistein / Q000633:toxicity*; D008297:Male; D008731:Methoxychlor / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010053:Ovary / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D010795:Phthalic Acids / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011301:Preoptic Area / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012733:Sex Differentiation / Q000187:drug effects; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000473:pathology
D010795:Phthalic Acids; C012125:diisononyl phthalate; D019833:Genistein; D008731:Methoxychlor