title: Gestational Zearalenone Exposure Causes Reproductive and Developmental Toxicity in Pregnant Rats and Female Offspring.
abstract: Zearalenone (ZEN) is an oestrogenic mycotoxin commonly found in food and feed products and can affect reproduction and development in both humans and animals. This study aimed to determine the toxic effects of ZEN on maternal SD rats and the F1 female offspring. Sixty-four pregnant rats were divided into 4 groups and exposed to feed contaminated with ZEN (0, 5, 10, and 20 mg/kg feed) on gestational days (GDs) 0-21. Compared with the controls, the groups exposed to 10 and 20 mg/kg ZEN showed significantly decreased feed intake and body weight of pregnant rats and/or female offspring. Meanwhile, 20 mg/kg ZEN significantly decreased the birth weight and viability of F1 newborn rats. Moreover, 10 and 20 mg/kg ZEN diets increased follicle-stimulating hormone concentrations but decreased oestradiol in both maternal and F1 adult rats. In the F1 generation, ZEN caused no pathological changes in ovaries and uterus in weaned rats, but significant follicular atresia and a thinning uterine layer were found in F1 female adult rats in the 20 mg/kg ZEN group. These impairments concurred with the inhibited mRNA and protein levels of oestrogen receptor-alpha (Esr1) and 3β-hydroxysteroid dehydrogenase (HSD) in the adult uterus and/or ovaries. Furthermore, 10 and/or 20 mg/kg ZEN exposure significantly reduced Esr1, gonadotropin-releasing hormone receptor (GnRHr), and ATP binding cassette transporters b1 and c1 (ABCb1 and ABCc1) in the placenta and foetal and weaned F1 brains, and also produced a dose-dependent increase in 3β-HSD in the placenta. Additionally, 20 mg/kg ZEN significantly upregulated ABCc5 expression in the placenta and ovaries of weaned rats. These results suggested that prenatal ZEN exposure in rats affected maternal and foetal development and may lead to long-term reproductive impairment in F1 adult females.
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. gaoxinnutrition@webmail.hzau.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. lvhuisun@mail.hzau.edu.cn.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, Hubei, China. lvhuisun@mail.hzau.edu.cn.
authors.forename: Lvhui
authors.initials: L
authors.lastname: Sun
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. zhangniya@mail.hzau.edu.cn.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, Hubei, China. zhangniya@mail.hzau.edu.cn.
authors.forename: Niya
authors.initials: N
authors.lastname: Zhang
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. chrisli@webmail.hzau.edu.cn.
authors.forename: Chong
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. zjcc404@126.com.
authors.forename: Jiacai
authors.initials: J
authors.lastname: Zhang
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. crystal_cuke@163.com.
authors.forename: Zhuohui
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: College of Animal Nutrition and Feed Science, Huazhong Agricultural University, Wuhan 430070, Hubei, China. qds@mail.hzau.edu.cn.|The Cooperative Innovation Center for Sustainable Pig Production, Wuhan 430070, Hubei, China. qds@mail.hzau.edu.cn.
authors.forename: Desheng
authors.initials: D
authors.lastname: Qi
mesh_terms: D000367:Age Factors; D000821:Animal Feed; D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D005516:Food Microbiology; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D018811:Maternal Exposure / Q000009:adverse effects*; D010053:Ovary / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D018570:Risk Assessment; D014599:Uterus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015025:Zearalenone / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D012333:RNA, Messenger; D004958:Estradiol; D015025:Zearalenone; D005640:Follicle Stimulating Hormone
keywords: F1 female rats; gestational exposure; transgenerational toxicity; zearalenone