PMID- 30315952 OWN - NLM STAT- MEDLINE DCOM- 20181109 LR - 20181109 IS - 1879-3169 (Electronic) IS - 0378-4274 (Linking) VI - 299 DP - 2018 Dec 15 TI - In utero exposure to hexavalent chromium disrupts rat fetal testis development. PG - 201-209 LID - S0378-4274(18)31993-3 [pii] LID - 10.1016/j.toxlet.2018.10.010 [doi] AB - Hexavalent chromium (Cr(6+)) acts as an endocrine disruptor. Herein, we investigated effects of Cr(6+) on the development of rat fetal Leydig and Sertoli cells, which support differentiation of the male reproductive tract in late gestation. Female pregnant Sprague Dawley rats were gavaged with potassium dichromate (0, 3, 6, and 12 mg/kg) from gestational days (GD) 12 to GD 21. Leydig and Sertoli cell function was evaluated by investigating serum testosterone levels, cell number and distribution, and the expression levels of Leydig and Sertoli cell genes and proteins. Cr(6+) increased serum testosterone level at dose of 3 mg/kg (1.170 +/- 0.121 ng/ml vs. 0.720 +/- 0.082 ng/ml in the control), while lowered it at dose of 12 mg/kg (0.400 +/- 0.098 ng/ml). In addition, it showed that Cr(6+) dose-dependently reduced Leydig cell size and cytoplasmic size and decreased the percentage of medium fetal Leydig cell cluster at dose of 12 mg/kg. Further study demonstrated that the expression of Leydig cell (Lhcgr, Scarb1, and Hsd3b1) and Sertoli cell (Fshr, Pdgfa, and Lif) genes in the testis was upregulated at dose of 3 mg/kg while the expression of Lhcgr, Hsd17b3 and Igf1 was downregulated by Cr(6+) at dose of 12 mg/kg. In conclusion, Cr(6+) had biphasic effects on fetal Leydig cell development with low dose to stimulate testosterone production and high dose to inhibit it, possibly via biphasically regulating growth factor gene expression in fetal Sertoli cells. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zheng, Wenwen AU - Zheng W AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Ge, Fei AU - Ge F AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Wu, Keyang AU - Wu K AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Chen, Xianwu AU - Chen X AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Li, Xiaoheng AU - Li X AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Chen, Yong AU - Chen Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Lv, Yao AU - Lv Y AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. FAU - Lian, Qingquan AU - Lian Q AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address: lianqingquanmz@163.com. FAU - Ge, Ren-Shan AU - Ge RS AD - Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China. Electronic address: r_ge@yahoo.com. LA - eng PT - Journal Article DEP - 20181010 PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Endocrine Disruptors) RN - 0R0008Q3JB (Chromium) RN - 18540-29-9 (chromium hexavalent ion) RN - 3XMK78S47O (Testosterone) SB - IM MH - Animals MH - Chromium/*toxicity MH - Dose-Response Relationship, Drug MH - Endocrine Disruptors/*toxicity MH - Female MH - Gene Expression Regulation, Developmental/drug effects MH - Leydig Cells/drug effects/metabolism MH - Male MH - Maternal Exposure/*adverse effects MH - Organogenesis/*drug effects/genetics MH - Pregnancy MH - Rats, Sprague-Dawley MH - Sertoli Cells/drug effects/metabolism MH - Testis/*drug effects/embryology MH - Testosterone/metabolism OTO - NOTNLM OT - Cell and cytoplasmic size OT - Cell distribution OT - Fetal Leydig cells OT - Fetal Sertoli cell OT - Hexavalent chromium OT - Testosterone EDAT- 2018/10/14 06:00 MHDA- 2018/11/10 06:00 CRDT- 2018/10/14 06:00 PHST- 2018/05/31 00:00 [received] PHST- 2018/09/30 00:00 [revised] PHST- 2018/10/08 00:00 [accepted] PHST- 2018/10/14 06:00 [pubmed] PHST- 2018/11/10 06:00 [medline] PHST- 2018/10/14 06:00 [entrez] AID - S0378-4274(18)31993-3 [pii] AID - 10.1016/j.toxlet.2018.10.010 [doi] PST - ppublish SO - Toxicol Lett. 2018 Dec 15;299:201-209. doi: 10.1016/j.toxlet.2018.10.010. Epub 2018 Oct 10.