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.

Individual and Combined Occurrence of Mycotoxins in Feed Ingredients and Complete Feeds in China

“…Both ZEN and DON are mainly produced by Fusarium . ZEN is an estrogenic toxin that competes with 17 β-estradiol for estrogen receptor binding, which consequently leads to fertility and reproductive problems [ 8 , 9 ]. In contrast, DON can induce anorexia, vomiting, and impairs immune function in various livestock species that involves inhibiting DNA, RNA, and protein synthesis [ 10 , 11 , 12 , 13 ].…”

Dietary exposure to mycotoxin zearalenone (ZEA) during post-implantation adversely affects placental development in mice

“…This situation is also implicated in studying the effect of ZEA on placental development. Several studies have alluded to the placenta as a target of ZEA: for example, ZEA can be bioactivated in placental cells [20]; ZEA and its metabolites can pass through placentas [21,22]; ZEA (2.76 ppm diet from D35 to D70 of pregnancy) can be accumulated in pig placentas and reduce placental and fetal weights [23], which may indicate impaired placental function that was not further investigated in the study; ZEA (20 ppm diet, from D0.5 to D20.5 of pregnancy) causes reduced birth weight of rats and reduced Esr1 (ERα) mRNA levels in the placentas but its effects on placental weight and placental morphology were not reported in the study [24]; rats exposed to 8 mg/kg body weight ZEA via gavage on D6-D19 had increased resorption of implantation sites and decreased fetal viability examined on D20, but the placentas were not examined in the study [25]. Since the placenta is the sole source of nutrients for supporting fetal development, the fetal toxicity from ZEA treatment could be a secondary effect of placental toxicity.…”

Single Nucleotide Polymorphisms in SLC5A1, CCNA1, and ABCC1 and the Association with Litter Size in Small-Tail Han Sheep

“…In mammalians, CCNA1 appears to be stage-specific and highly expressed in germ cells [31,43]. ABCC1 is widely expressed in various tissues and plays an important role in uteroplacental transport signaling [44,45]. In addition, it was reported that the hypothalamic–pituitary–gonadal axis (HPG) is the most important system for controlling mammalian reproduction [46].…”