Effect of Wuzi Yanzong Pills on Sertoli cells and blood–testis barrier in heat‐stressed rats based on Akt signalling pathway

Abstract

The blood–testis barrier (BTB) of Sertoli cells (SCs) is an important biological barrier that maintains spermatogenesis and provides a favourable microenvironment for spermatogenesis. However, heat stress can directly damage the BTB structural proteins of testicular SCs, leading to dyszoospermia. Wuzi Yanzong Pills (WYP) is a traditional Chinese medicine formula used to treat male reproductive diseases. However, whether WYP could ameliorate heat stress injury in primary SCs extracted from rat testes and BTB proteins remains unknown. Here, treatment with WYP (low, medium and high dose) increased the SC viability and the proliferation of cell antigen Ki67 significantly. Additionally, it promoted SC maturation, which presented in the form of increased androgen receptors (ARs) and decreased cytokeratin 18 (CK‐18) in three WYP dose groups. WYP upregulated BTB proteins such as zonula occludens 1 (ZO‐1) and occludin across all WYP groups and decreased phosphorylated Akt (p‐Akt) in the middle and high‐dose groups; however, ZO‐1 and occludin recovery were reduced with the presence of Akt inhibitor in WYP groups. WYP improved SC viability and proliferation, and ameliorated dedifferentiation and BTB‐proteins damaged by heat stress via Akt signalling. The findings present theoretical support for the effects of WYP in the management of dyszoospermia and male infertility.

ALKBH5 in mouse testicular Sertoli cells regulates Cdh2 mRNA translation to maintain blood–testis barrier integrity

“…Therefore, maintaining BTB integrity is an important basis for normal spermatogenesis. Fortunately, some drugs, such as Lycium barbarum polysaccharide [ 43 ] and traditional Chinese medicine [ 44 , 45 ], have been found to maintain BTB integrity and promote spermatogenesis. In this study, we confirmed that ALKBH5 in Sertoli cells is involved in regulating BTB integrity.…”

The traditional Chinese medicine Qiangjing tablet prevents blood‐testis barrier injury induced by CdCl2 through the PI3K/Akt/Rictor signaling pathway

“…Wu‐Zi‐Yan‐Zong‐Wan may ameliorate BTB dysfunction by regulating proinflammatory cytokine levels 38,39 . Icariina prevents the degradation of gap junction intercellular communication and impairment of connexin 43 in the BTB that are induced by microcystin‐leucine‐arginine 40 . Lycium barbarum polysaccharide can ameliorate the damage to the structural integrity of the BTB induced by heat stress 41 .…”

“…38,39 Icariina prevents the degradation of gap junction intercellular communication and impairment of connexin 43 in the BTB that are induced by microcystin-leucine-arginine. 40 Lycium barbarum polysaccharide can ameliorate the damage to the structural integrity of the BTB induced by heat stress. 41 QJP can upregulate the PI3K/Akt/Rictor signaling pathway by altering p-Akt/t-Akt, PI3K p85α, PI3K 110β and Rictor expression.…”

Research progress on Wuzi Yanzong pills in the treatment of male infertility

“…Studies have shown that WZYZP has a developmental and proliferative effect on supporting cells in both physiological and pathological states in mice and rats and can promote male reproductive function by potentially activating the Akt signaling pathway. [55,56] Zhang et al [57] found that WZYZP-containing serum promoted supporting cell viability in normal rats. Furthermore, WZYZP is capable of repairing damaged supporting cell cytoskeleton, regulating their expression, promoting supporting cell differentiation and maturation, and governing the secretory function of supporting cells, thereby inhibiting the apoptosis of spermatogenic cells.…”

“…Wuzi Yanzong pill has been implicated in the regulation of several signaling pathways. Wuzi Yanzong pill promotes Akt phosphorylation, thereby promoting supporting cell differentiation [56] and proliferation [55] by activating Akt signaling pathway, improving BTB protein damaged by heat stress, and subsequently improving spermatogenesis disorders. [56] Furthermore, studies have shown that WZYZP ameliorates testicular heat stress–induced spermatogenesis disorder by regulating Akt and nuclear factor κB (NF-κB) signaling pathways.…”