PMID- 32388187 OWN - NLM STAT- MEDLINE DCOM- 20201217 LR - 20201217 IS - 1090-2414 (Electronic) IS - 0147-6513 (Linking) VI - 198 DP - 2020 Jul 15 TI - In utero exposure to DBP stimulates release of GnRH by increasing the secretion of PGE2 in the astrocytes of the hypothalamus in the offspring mice. PG - 110698 LID - S0147-6513(20)30537-6 [pii] LID - 10.1016/j.ecoenv.2020.110698 [doi] AB - Di-n-butyl phthalate (DBP), the most commonly used plasticizer and typical endocrine disrupting chemicals (EDCs), has shown its characteristics of causing reproductive and developmental toxicity in males, while the neuroendocrine toxicity induced by DBP exposure in utero and the mechanism beneath still remain unclear. Here, the pregnant mice were treated with corn oil (control) or DBP at three different doses by oral gavage during gestational days (GD) 12.5-21.5. The results showed that in utero exposure to DBP induced a significant increase of gonadotropin releasing hormone (GnRH) content in serum, as well as activation and proliferation of astrocytes in the hypothalamus of offspring male mice on postnatal day (PND) 22. However, in in vitro study, mono-n-butyl phthalate (MBP), the metabolite of DBP, could not increase the release of GnRH after GnRH neurons were exposed to MBP. Further studies identified that MBP-mediated activation and proliferation of astrocytes resulted in increased secretion of prostaglandin E2 (PGE2), which might be responsible for the increased release of GnRH from GnRH neurons. This study highlights the neuroendocrine toxicity of current plasticizer DBP exposure, laying the foundation for identifying potential molecular targets for related diseases. CI - Copyright (c) 2020 Elsevier Inc. All rights reserved. FAU - Xia, Yunhui AU - Xia Y AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Ma, Tan AU - Ma T AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Ji, Jie AU - Ji J AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Zhang, Liupan AU - Zhang L AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Wang, Yu AU - Wang Y AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Wu, Jiang AU - Wu J AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Ding, Jie AU - Ding J AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. FAU - Han, Xiaodong AU - Han X AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: hanxd@nju.edu.cn. FAU - Li, Dongmei AU - Li D AD - Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu, 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu, 210093, China. Electronic address: lidm@nju.edu.cn. LA - eng PT - Journal Article DEP - 20200507 PL - Netherlands TA - Ecotoxicol Environ Saf JT - Ecotoxicology and environmental safety JID - 7805381 RN - 0 (Endocrine Disruptors) RN - 0 (Phthalic Acids) RN - 2286E5R2KE (Dibutyl Phthalate) RN - 33515-09-2 (Gonadotropin-Releasing Hormone) RN - K7Q1JQR04M (Dinoprostone) RN - ZI46LWZ45G (monobutyl phthalate) SB - IM MH - Animals MH - Astrocytes MH - Bodily Secretions MH - Dibutyl Phthalate/*toxicity MH - Dinoprostone MH - Endocrine Disruptors/*toxicity MH - Female MH - Gonadotropin-Releasing Hormone/*metabolism MH - Hypothalamus/*physiology MH - Male MH - Mice MH - Neurons MH - Phthalic Acids MH - Pregnancy MH - Reproduction OTO - NOTNLM OT - Astrocytes OT - Di-n-butyl phthalate (DBP) OT - Gonadotropin releasing hormone (GnRH) OT - Mono-n-butyl phthalate (MBP) OT - Prostaglandin E2 (PGE2) COIS- Declaration of competing interest The authors report no conflicts of interest. EDAT- 2020/05/11 06:00 MHDA- 2020/12/18 06:00 CRDT- 2020/05/11 06:00 PHST- 2020/03/24 00:00 [received] PHST- 2020/04/26 00:00 [revised] PHST- 2020/04/28 00:00 [accepted] PHST- 2020/05/11 06:00 [pubmed] PHST- 2020/12/18 06:00 [medline] PHST- 2020/05/11 06:00 [entrez] AID - S0147-6513(20)30537-6 [pii] AID - 10.1016/j.ecoenv.2020.110698 [doi] PST - ppublish SO - Ecotoxicol Environ Saf. 2020 Jul 15;198:110698. doi: 10.1016/j.ecoenv.2020.110698. Epub 2020 May 7.