title: Di (2-ethylhexyl) phthalate impairs steroidogenesis in ovarian follicular cells of prepuberal mice.
abstract: Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer which is widely used in the manufacture of plastics. As a common environmental contaminant and recognized endocrine disrupting chemical, DEHP is able to deregulate the functions of a variety of tissues, including the reproductive system both in males and females. In order to investigate the possible effects of DEHP on the first wave of folliculogenesis, occurring in the mouse ovary postnatally, mice were administered 20 or 40 μg/kg DEHP through intraperitoneal injection at days 5, 10 and 15 post partum (dpp). Following DEHP treatment the gene expression profile of control and exposed ovaries was compared by microarray analyses at 20 dpp. We found that in the exposed ovaries DEHP significantly altered the transcript levels of several immune response and steroidogenesis associated genes. In particular, DEHP significantly decreased the expression of genes essential for androgen synthesis by theca cells including Lhcgr, Cyp17a1, Star and Ldlr. Immunohistochemistry and immune flow cytometry confirmed reduced expression of LHCGR and CYP17A1 proteins in the exposed theca cells. These effects were associated to a significant reduction in ovarian concentrations of progesterone, 17β-estradiol and androstenedione along with a reduction of LH in the serum. Although we did not find a significant reduction of the number of primary, secondary or antral follicles in the DEHP exposed ovaries when compared to controls, we did observe that theca cells showed an altered structure of the nuclear envelope, fewer mitochondria, and mitochondria with a reduced number of cristae. Collectively, these results demonstrate a deleterious effect of DEHP exposure on ovarian steroidogenesis during the first wave of folliculogenesis that could potentially affect the correct establishment of the hypothalamic-pituitary-ovarian axis and the onset of puberty.
authors.affiliation: College of Life Science, Qingdao Agricultural University, Qingdao, 266109, China.|Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.
authors.forename: Fang-Nong
authors.initials: FN
authors.lastname: Lai
authors.affiliation: College of Life Science, Qingdao Agricultural University, Qingdao, 266109, China.|Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.
authors.forename: Jing-Cai
authors.initials: JC
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.|College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.
authors.forename: Jun-Yu
authors.initials: JY
authors.lastname: Ma
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.
authors.forename: Xue-Lian
authors.initials: XL
authors.lastname: Liu
authors.affiliation: Hospital of School, Qingdao Agricultural University, Qingdao, 266109, China.
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China.|College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, 430023, China.
authors.forename: Xi-Feng
authors.initials: XF
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, 712100, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: De Felici
authors.affiliation: Department of Animal Sciences, Auburn University, Auburn, AL, 36849, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Dyce
authors.affiliation: Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, 266109, China. wshen@qau.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
mesh_terms: D000818:Animals; D004051:Diethylhexyl Phthalate / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006107:Granulosa Cells / Q000187:drug effects / Q000648:ultrastructure; D008815:Mice, Inbred Strains; D020411:Oligonucleotide Array Sequence Analysis; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000502:physiology; D011627:Puberty; D013256:Steroids / Q000378:metabolism*
chemical_list: D013256:Steroids; D004051:Diethylhexyl Phthalate
keywords: Di (2-ethylhexyl) phthalate; Folliculogenesis; Pre-puberty mice; Steroidogenesis