Exposure to triptolide affects follicle development in NIH mice

Abstract

<jats:p> Triptolide (TPL) is a main active compound isolated from Tripterygium wilfordii Hook f. Despite its positive therapeutic effect, the female reproductive toxicity of TPL is still the bottleneck of clinical application. The study was designed to investigate the adverse effects on mice ovary and underlying mechanism of TPL. Adult female NIH mice were treated with two therapeutic doses of TPL (25 and 50 μg/kg/d) for 50 days, respectively. Mice estrous cycle was detected by vaginal cytology method. Half mice from each group were selected randomly to perform superovulation. Quality and quantity of ovulated eggs were evaluated. Other mice from each group were executed for morphological study. Ovarian histological sections were stained by H&amp;E staining for ovarian pathologic detection and follicular counts. Apoptotic granulosa cell (GC) was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Endoplasmic reticulum (ER) stress-related proteins and antiapoptotic X-linked inhibitor of apoptosis protein (XIAP) were detected by immunohistochemical method. Two doses of TPL resulted in estrous cycle disorder and follicles in development reservoir impairment. Quality and quantity of mice ovulated eggs significantly decreased after TPL treatment. Ovarian pathologic examination revealed TPL-induced TUNEL-positive GCs increase and ER stress–related proteins (78-kDa glucose-regulated protein, p-protein kinase-like endoplasmic reticulum kinase, p-eukaryotic initiation factor 2α, and CCAAT/enhancer binding protein homologous protein) expression upregulation. Meanwhile, the expression of antiapoptosis protein XIAP in mice ovary was obviously inhibited by TPL. Our results may demonstrate that therapeutic doses of TPL can injure ovary function, but there is no difference between high-dose and low-dose groups. GCs apoptosis by ER stress pathway and antiapoptotic function impairment may partly mediate TPL-induced ovary toxicity. </jats:p>

Comparison of different intracellular cryoprotectants on the solid surface vitrification of red‐rumped agouti (Dasyprocta Leporina Lichtenstein, 1823) ovarian tissue

“…TUNEL control tissue and vitrified sections were included in all evaluations, according to the manufacturer's recommendations. Only follicles with visible oocyte nuclei were analysed(Zeng et al, 2017).…”

The effects of natural products and bioactive ingredients of traditional Chinese medicine on apoptosis of ovarian granulosa cells

“…that was reported to inhibit follicle growth and mutations, while promoting follicular atresia. The apoptotic index of GCs treated with triptolide at 50 μg/kg/day is reportedly 82.8‰ ± 7.1‰ (Zeng et al, 2017). In addition, treatment with plumbagin at 1, 5, and 100 μM for 24 h increased the proportion of apoptotic GCs and was associated with inhibition of the phosphoinositide 3‐kinase‐serine/threonine‐protein kinase/mechanistic target of rapamycin (PI3K/AKT/mTOR) signaling pathway (Cai et al, 2020).…”

Sigma-1 receptor is involved in diminished ovarian reserve possibly by influencing endoplasmic reticulum stress-mediated granulosa cells apoptosis

“…Earlier research found that GCs apoptosis was predominantly mediated by the celldeath ligand/receptor-dependent pathway [59]. Recent studies have paid more attention to ERS-mediated apoptotic pathways [60][61][62][63]. The ER is an important subcellular compartment involved in mitochondrion-dependent apoptosis [64,65], and ERS is a complicated adaptive reaction caused by certain stimulus [65].…”