Zearalenone (ZEA) is present worldwide as a serious contaminant of food and feed and causes male reproductive toxicity. The implication of paraptosis, which is a nonclassical paradigm of cell death, is unclear in ZEA-induced male reproductive disorders. In this study, the toxic effects of ZEA on the blood-testis barrier (BTB) and the related mechanisms of paraptosis were detected in goats. ZEA exposure, in vivo, caused a significant decrease in spermatozoon quality, the destruction of seminiferous tubules, and damage to the BTB integrity. Furthermore, ZEA exposure to Sertoli cells (SCs) in vitro showed similar dysfunction in structure and barrier function. Importantly, the formation of massive cytoplasmic vacuoles in ZEA-treated SCs corresponded to the highly swollen and dilative endoplasmic reticulum (ER), and paraptosis inhibition significantly alleviated ZEA-induced SC death and vacuolization, which indicated the important contribution of paraptosis in ZEA-induced BTB damage. Meanwhile, the expression of ER stress marker proteins was increased after ZEA treatment but decreased under the inhibition of paraptosis. The vacuole formation and SC death, induced by ZEA, were remarkably blocked by ER stress inhibition. In conclusion, these results facilitate the exploration of the mechanisms of the SC paraptosis involved in ZEA-induced BTB damage in goats.

Improving the reproductive ability and fertility of male ruminants is a central concern in animal husbandry. Phytogenic feed additives, known for their anti-inflammatory, antioxidant, and immunomodulatory properties, are commonly used in animal feed. Icariin (ICA), the primary flavonoid glucoside derived from Epimedium, is a traditional tonic in Chinese herbal medicine. However, its potential to enhance the reproductive performance of male ruminants remains unclear. In this study, twelve healthy adult male dairy goats were divided into two groups. The goats received oral administration of ICA at doses of 0 (control) and 50 mg/kg body weight daily for a consecutive period of 80 days during the breeding season. The effects of ICA on the reproductive performance was analyzed by histological examinations, semen quality analysis, and ELISA experiments. ELISA results showed a progressive increase in serum levels of GnIH, LH, and testosterone with the prolonged ICA treatment (p < 0.05). However, the serum concentration of GnRH in the ICA group initially increased, followed by a subsequent decrease (p < 0.05). The hypothalamic concentrations of dopamine (DA) and 5-hydroxytryptamine (5-HT) were significantly higher in the ICA group compared to the control group (p < 0.01). The CASA system analyzed sperm kinematics and revealed that ICA increased ejaculate volume, with both total motile and progressive motile sperm gradually increasing over time (p < 0.05). ICA did not affect the body weight of the goats but significantly increased the organ coefficient of the testes (p < 0.01). Additionally, there was an upregulation of hormone receptor expression in testicular tissue and an improvement in the antioxidant capacity of the testes after ICA treatment (p < 0.01). Furthermore, ICA was implicated in testosterone synthesis by modulating the expression of key enzymes associated with steroidogenesis and promoting the differentiation of spermatogonial stem cell to enhance spermatogenesis. In conclusion, our results indicate that icariin, as a phytogenic feed additive incorporated into the diet of ruminants, offers potential benefits in improving the reproductive performance of male dairy goats.