title: Zearalenone exposure impairs ovarian primordial follicle formation via down-regulation of Lhx8 expression in vitro.
abstract: Zearalenone (ZEA) is an estrogenic mycotoxin mainly produced as a secondary metabolite by numerous species of Fusarium. Previous work showed that ZEA had a negative impact on domestic animals with regard to reproduction. The adverse effects and the mechanisms of ZEA on mammalian ovarian folliculogenesis remain largely unknown, particularly its effect on primordial follicle formation. Thus, we investigated the biological effects of ZEA exposure on murine ovarian germ cell cyst breakdown and primordial follicle assembly. Our results demonstrated that newborn mouse ovaries exposed to 10 or 30μM ZEA in vitro had significantly less germ cell numbers compared to the control group. Moreover, the presence of ZEA in vitro increased the numbers of TUNEL and γH2AX positive cells within mouse ovaries and the ratio of mRNA levels of the apoptotic genes Bax/Bcl-2. Furthermore, ZEA exposure reduced the mRNA of oocyte specific genes such as LIM homeobox 8 (Lhx8), newborn ovary homeobox (Nobox), spermatogenesis and oogenesis helix-loop-helix (Sohlh2), and factor in the germline alpha (Figlα) in a dose dependent manner. Exposure to ZEA led to remarkable changes in the Lhx8 3'-UTR DNA methylation dynamics in oocytes and severely impaired folliculogenesis in ovaries after transplantation under the kidney capsules of immunodeficient mice. In conclusion, ZEA exposure impairs mouse primordial follicle formation in vitro.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
authors.forename: Guo-Liang
authors.initials: GL
authors.lastname: Zhang
authors.affiliation: Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Sun
authors.affiliation: Institute of Animal Sciences, Heilongjiang Academy of Agricultural Sciences, Harbin, Heilongjiang 150086, China.
authors.forename: Yan-Zhong
authors.initials: YZ
authors.lastname: Feng
authors.affiliation: Chengguo Station of Animal Husbandry and Veterinary, Laizhou 261437, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Li
authors.affiliation: Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Animal Science, University of Manitoba, Winnipeg, MB, R3T 2N2, Canada.
authors.forename: Charles Martin
authors.initials: CM
authors.lastname: Nyachoti
authors.affiliation: Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: ssdsm@tom.com.
authors.forename: Shi-Duo
authors.initials: SD
authors.lastname: Sun
authors.affiliation: Institute of Reproductive Sciences, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao, Shandong 266109, China. Electronic address: lilan9600@126.com.
authors.forename: Lan
authors.initials: L
authors.lastname: Li
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D005786:Gene Expression Regulation; D060850:LIM-Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051379:Mice; D016513:Mice, SCID; D006080:Ovarian Follicle / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D015025:Zearalenone / Q000633:toxicity*
chemical_list: D004968:Estrogens, Non-Steroidal; C112960:LIM homeobox protein 8; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D015025:Zearalenone
keywords: Folliculogenesis; Lhx8; Primordial follicle formation; Zearalenone