The joint action of unfolded protein response, circZc3h4, and circRNA Scar in procymidone‐induced testicular injury in adolescent mice

Abstract

Procymidone (PCM) is a low toxicity fungicide, and an endocrine‐disrupting chemical (EDC) that particularly damages the reproductive system of male vertebrates. In present study, adolescent mice in control, low‐, medium‐, and high‐dose groups were orally administered 0 (equal volume of soybean oil), 50, 100, and 200 mg/kg/day PCM, respectively, for 21 days. Additionally, a three‐dimensional culture of mouse testes was performed in vitro, and the control, low dose (0.33 × 10−5 M), medium dose (1 × 10−5 M), and high dose (3 × 10−5 M) PCM groups were established. We have found that, under both in vivo and in vitro conditions, all doses of PCM caused damage to mouse testes. Moreover, the levels of circZc3h4 RNA and Zc3h4 decreased while miR‐212 increased in all treatment groups, with a corresponding rise in circRNA Scar and fall in Atp5b, compared to those in the control group, and all the changes showed a dose–response relationship. Besides, we have identified that low doses of PCM could activate the Ire1‐Xbp1 pathway, whereas the medium and high doses activated the Perk‐Elf2α‐Atf4, Ire1‐Xbp1, and Atf6 pathways. And it is, therefore, speculated that the unfolded protein response (UPR), circZc3h4 and circRNA Scar may have taken joint action in testicular injury in adolescent mice induced by PCM at the no observed adverse effect level (NOAEL, 100 mg/kg/day) and below NOAEL doses.

Effects of maternal exposure to procymidone on hepatic metabolism in the offspring of mice

“…Dams in the control group were given a regular diet during pregnancy and lactation, while the other two groups were treated with PRO 10 (PRO‐L) and 100 mg/kg body weight/day (PRO‐H), respectively. The concentration of PRO exposure was based on the level of no‐observed adverse effect level (NOAEL), 30 specified by the FAO/WHO Joint Conference on pesticide residues (JMPR).…”

Hsa_circ_0008500 inhibits apoptosis of adipose‐derived stem cells under high glucose through hsa‐miR‐1273h‐5p/ELK1 axis

“…Recently, circular RNAs (circRNAs) have been revealed to be vital molecules in genetic expression modulation on the post‐transcription level 9,10 . CircRNAs are derived from a non‐canonical form of variable splicing, where the splice donor spot of one exon is ligated to the splice acceptor spot of an up stream exon 11 .…”

“…Recently, circular RNAs (circRNAs) have been revealed to be vital molecules in genetic expression modulation on the post-transcription level. 9,10 CircRNAs are derived from a non-canonical form of variable splicing, where the splice donor spot of one exon is ligated to the splice acceptor spot of an up stream exon. 11 Diverse from linearity RNA, circRNAs produce a continuous steady loop framework in the Fandong Meng and Fengjie Shen contributed equally to this study.…”

The identification and functional analysis of CircRNAs in endometrial receptivity of mice with polycystic ovary

“…9,10 Due to its unique molecular structure, circRNA is more stable and conserved than other RNA types, making it a more suitable biomarker. [11][12][13] Recent evidence demonstrates that circRNAs have multiple biological functions, including cis-acting regulation of host gene expression, regulation of miRNA target genes by acting as miRNA sponges, protein translation, and protein interaction. 14 CircRNAs have been implicated in a variety of pathological and physiological processes, including various types of malignant cancer, cardiovascular disease, and endocrine dysfunctions.…”

“…14 CircRNAs have been implicated in a variety of pathological and physiological processes, including various types of malignant cancer, cardiovascular disease, and endocrine dysfunctions. 13,[15][16][17] Recent research has demonstrated that circRNA is essential for developing endometrial receptivity and embryo implantation. Song et al discovered that several circRNAs were differentially expressed in the endometrium of dairy goats and suggested that circRNAs may be potential regulators of receptive endometrium.…”