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Animal Age-Dependent Susceptibility of Mouse Oocytes to Zearalenone-Induced Developmental Impairment: Roles of Pharmacokinetic Exposure and Intrinsic Oocyte Sensitivity
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DOI：10.3390/cells15161444.png)
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Abstract
En 中文
Background: Zearalenone (ZEN) exposure poses health risks to both humans and animals. Although evidence indicates that ZEN significantly impairs oocyte developmental competence, the underlying mechanisms remain largely unclear. While it is recognized that prepubertal animals are particularly vulnerable to ZEN and that juvenile in vitro embryo transfer represents a promising strategy for accelerating genetic progress, the potential impact of ZEN on developmental competence of prepubertal oocytes remains uninvestigated. Methods: In vivo, we administered graded oral doses of ZEN to female mice at prepubertal (3 weeks), peripubertal (6 weeks), and post-pubertal (8 weeks) stages and assessed oocyte developmental potential and related markers and ZEN residues in ovaries and livers following superovulation. In vitro, oocytes isolated from mice of each age group were subjected to graded ZEN concentrations during in vitro maturation, followed by evaluation of oocyte developmental potential. Results: This study shows that oral ZEN exposure impairs oocyte developmental competence and cumulus expansion, and disrupts oocyte redox homeostasis, mitochondrial integrity and glutathione biosynthesis in a mouse age-specific manner, with prepubertal (3-week-old) mice exhibiting the greatest susceptibility. Assessment of systemic ZEN disposition shows that ZEN concentrations in both ovarian and hepatic tissues were significantly higher in 3-week-old mice than in 6- and 8-week-old mice. Furthermore, exposure of oocytes to graded ZEN concentrations during in vitro maturation demonstrate that oocytes from prepubertal mice exhibit intrinsically heightened susceptibility to ZEN-induced functional deficits relative to those from sexually mature adults. Conclusions: This study demonstrates that ZEN exposure compromises oocyte developmental competence in a host age-dependent manner, and the heightened vulnerability in prepubertal oocytes is associated with both increased ovarian ZEN bioavailability and their intrinsically greater sensitivity to ZEN.
Keywords:
bioavailability
developmental competence
oocytes
prepuberty
zearalenone
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