Abstract：Objective The objectives of this study were to investigate the effects of exposure to TCDD in utero on early ovarian function in neonatal female rats. Methods Beginning at gestational day 13 (GD13), female SD rats were intragastric administrated with a range of low-doses of TCDD (5, 100, and 500 ng/kg/2d) or coin oil until labor every two days. Serum concentrations of estradiol and progesterone at postnatal day 3 (PND3) rats were measured with the electro-chemiluminescence immunoassay (ECLIA). Ovarian morphology and ultrastructure of PND3 rats were observed using HE-stain and transmission electron microscope. The number of primordial follicles and primary follicles were counted. Results TCDD treatment decreased serum Estradiol 2 (E2) and Progesterone (P) concentrations [(5.4±0.4) pg/ml and (35.4±3.2) pg/ml, respectively] of PND3 pups. There were significant differences in serum E2 and P concentrations in female between 500 ng/kg/2d and other groups. No differences in numbers of primordial follicles and primary follicles were found between the control and TCDD treated groups. Ovarian structure of the female pup was affected pathologically, and the harmful effects were significance in 500 ng/kg/2d group. The main ultrastructural findings related to the oocytes of the experimental group were shrunk, pyknotic nuclei, and degenerative mitochondria in the ooplasm. Furthermore, the granulosa cells revealed disorganization and integrity. Conclusion Gestational exposure to mild dosage of TCDD significantly perturbs ovarian ultrastructure and endocrine in PND3 female rats. TCDD exposure in utero had dramatically reproductive toxicity effects on ovary of neonatal pups.
1 Wesselink A,Warner M,Samuels S,et al.Maternal dioxin exposure and pregnancy outcomes over 30 years of follow-up in Seveso.Environ Int,2014,63:143-148. 2 Patandin S,Dagnelie PC,Mulder PG,et al.Dietary exposure to polychlorinated biphenyls and dioxins from infancy until adulthood:A comparison between breast-feeding,toddler,and long-term exposure.Environ Health Perspect,1999,107:45-51. 3 Nishijo M,Tawara K,Nakagawa H,et al.2,3,7,8-Tetrachlorodibenzo-p-dioxin in maternal breast milk and newborn head circumference.J Expo Sci Environ Epidemiol,2008,18:246-251. 4 Baccarelli A,Giacomini SM,Corbetta C,et al.Neonatal thyroid function in Seveso 25 years after maternal exposure to dioxin.PLoS Med,2008,5:e161. 5 Bruner-Tran KL,Osteen KG.Developmental exposure to TCDD reduces fertility and negatively affects pregnancy outcomes across multiple generations.Reprod Toxicol,2011,31:344-350. 6 吴迪,李练兵,马明福.二恶英及其类似物的生殖毒性研究进展.中国生育健康杂志,2014,25:388-390. 7 Myllymaki SA,Haavisto TE,Brokken LJ,et al.In utero and lactational exposure to TCDD; steroidogenic outcomes differ in male and female rat pups.Toxicol Sci,2005,88:534-44. 8 Franczak A,Nynca A,Valdez KE,et al.Effects of acute and chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin on the transition to reproductive senescence in female Sprague-Dawley rats.Biol Reprod,2006,74:125-130. 9 Shi Z,Valdez KE,Ting AY,et al.Ovarian endocrine disruption underlies premature reproductive senescence following environmentally relevant chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin.Biol Reprod,2007,76:198-202. 10 Brunnberg S,Andersson P,Poellinger L,et al.The constitutively active Ah receptor (CA-AhR) mouse as a model for dioxin exposure-effects in reproductive organs.Chemosphere,2011,85:1701-1706. 11 Pesonen SA,Haavisto TE,Viluksela M,et al.Effects of in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on rat follicular steroidogenesis.Reprod Toxicol,2006,22:521-528. 12 许虹,许振成,张素坤,等.2,3,7,8-四氯二苯并对二噁英诱导原代培养大鼠卵巢颗粒细胞的氧化应激和凋亡.毒理学杂志,2011,25:9-13. 13 许振成,许虹,张素坤,等.2,3,7,8-四氯二苯并对二噁英对大鼠卵巢颗粒细胞雌二醇和孕酮分泌的影响.生态毒理学报,2009,4:131-135. 14 Fowler PA,Dora NJ,McFerran H,et al.In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep.Mol Hum Reprod,2008,14:269-80.
