Effects of perinatal exposure of five putative endocrine disrupting chemicals (EDCs), methoxychlor, genistein, diisononylphthalate 4-nonylphenol and bisphenol A, on endocrine/reproductive systems in rats
Takagi, H; Shibutani, M; Masutomi, N; Uneyama, C; Mitsumori, K; Hirose, M
Methoxychlor (MXC, 24, 240, 1200 ppm), genistein (GEN, 20, 200, 1000 ppm), diisononylphthalate (DINP, 400, 4000, 20,000 ppm), 4-nonylphenol (NP, 60, 600, 3000 ppm) or bisphenol A (BA, 60, 600, 3000 ppm) were given to maternal rats from gestational day 15 to postnatal day (PND) 10 to assess their perinatal exposure effects on offsprings. Soybean-free diet was used as a basal diet. Organ weights at PND21, onset of puberty, estrous cyclicity, gonadotrophin-immunopositive index (IPI) in pituitary at PND21 and 77, and histological changes at PND77 were assessed as well as the size of sexually dimorphic nucleus of preoptic area (SDN-POA). In terms of MXC, DINP and GEN studies, expression of GABA transporter-1 (GAT-1), an estrogen responsive gene, was analyzed in medial preoptic area (MPOA) at PND10 using microdissection and real-time RT-PCR techniques. Females exposed to 1200 ppm MXC showed accelerated onset of puberty, irregular estrous cyclicity, histological changes such as multifollicular ovaries, hyperplasia in endometrium, vaginal mucosa and anterior pituitary at PND77, and decrease in LH-IPI at PND21 and increase in FSH- and PRL-IPIs at PND77. Females of 240 ppm MXC also showed increased PRL-IPI at PND77. Males of 1200 ppm MXC showed delayed onset of puberty and decreased LH-, FSH- and PRL-IPIs at PND21. DINP at 20,000 ppm caused very slight degeneration of spermatocytes and Sertoli cells at PND77. The sizes of SDN-POA did not alter at any doses of chemicals examined. GAT-1 levels in male MPOAs decreased with DINP at 20,000 ppm, and also showed a dose-related decreasing tendency with MXC. GEN, BA and NP did not affect any endocrine parameter examined. Results suggest that maternal exposure to MXC and DINP affects reproductive system of offsprings by disrupting brain sexual differentiation.
