PMID- 14580783 OWN - NLM STAT- MEDLINE DCOM- 20031224 LR - 20190819 IS - 0300-483X (Print) IS - 0300-483X (Linking) VI - 192 IP - 2-3 DP - 2003 Nov 5 TI - 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. PG - 149-70 AB - 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. FAU - Masutomi, Naoya AU - Masutomi N AD - Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. FAU - Shibutani, Makoto AU - Shibutani M FAU - Takagi, Hironori AU - Takagi H FAU - Uneyama, Chikako AU - Uneyama C FAU - Takahashi, Noriyuki AU - Takahashi N FAU - Hirose, Masao AU - Hirose M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Ireland TA - Toxicology JT - Toxicology JID - 0361055 RN - 0 (Phthalic Acids) RN - 4010KIX4CK (diisononyl phthalate) RN - DH2M523P0H (Genistein) RN - RIA79UD69L (Methoxychlor) SB - IM MH - Administration, Oral MH - Animals MH - Body Weight/drug effects MH - Endocrine System/*drug effects/growth & development MH - Estrous Cycle/drug effects MH - Female MH - Genistein/*toxicity MH - Male MH - Methoxychlor/*toxicity MH - Organ Size/drug effects MH - Ovary/drug effects/growth & development/pathology MH - Phthalic Acids/*toxicity MH - Pregnancy MH - *Prenatal Exposure Delayed Effects MH - Preoptic Area/drug effects/growth & development/pathology MH - Rats MH - Rats, Sprague-Dawley MH - Reproduction/*drug effects MH - Sex Differentiation/drug effects MH - Testis/drug effects/growth & development/pathology EDAT- 2003/10/29 05:00 MHDA- 2003/12/25 05:00 CRDT- 2003/10/29 05:00 PHST- 2003/10/29 05:00 [pubmed] PHST- 2003/12/25 05:00 [medline] PHST- 2003/10/29 05:00 [entrez] AID - S0300483X03002695 [pii] AID - 10.1016/s0300-483x(03)00269-5 [doi] PST - ppublish SO - Toxicology. 2003 Nov 5;192(2-3):149-70. doi: 10.1016/s0300-483x(03)00269-5.