The endoplasmic reticulum stress and related signal pathway mediated the glyphosate-induced testosterone synthesis inhibition in TM3 cells

Xia, Yong-Peng; Yang, Xiaobo; Lu, Jingchun; Xie, Qixin; Ye, Anfang; Sun, Wenjun

doi:10.1016/j.envpol.2020.113949

Cited by 29 publications

(9 citation statements)

References 39 publications

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“…In addition, we have recently showed that Zearalenone exposure impaired GRP78 expression, resulting in failure of oocyte maturation. Moreover, a previous study has showed that glyphosate induces ER stress in TM3 cells [49]. Therefore, we suggested that glyphosate disrupted the homeostasis and functions of ER, which may further damage porcine oocyte maturation.…”

Section: Discussionmentioning

confidence: 77%

Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs

Chen

Wang

Pan

et al. 2022

J Animal Sci Biotechnol

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Background Recently, defects in mammalian oocytes maturation induced by environmental pollution results in the decreasing animal reproduction. Animal exposed to glyphosate is largely unavoidable because glyphosate is one of the most widely used herbicide worldwide due to its high-efficiency and broad-spectrum effects, which causes glyphosate an environmental contaminant found in soil, water and food. During the last few years, the growing and wider use of glyphosate has raised great concerns about its effects of reproductive toxicity. In this study, using porcine models, we investigated effects of glyphosate on organelle functions during oocyte meiosis. Results The results showed glyphosate exposure disrupted porcine oocyte maturation. Expression levels of cumulus expansion-related genes were interfered, further indicating the meiotic defects. The damaging effects were mediated by destruction of mitochondrial distribution and functions, which induced ROS accumulation and oxidative stress, also indicated by the decreased mRNA expression of related antioxidant enzyme genes. We also found an interference of endoplasmic reticulum (ER) distribution, disturbance of Ca2+ homeostasis, as well as fluctuation of ER stress, showing with the reduced ER stress-related mRNA or protein expression, which could indicate the dysfunction of ER for protein processing and signal transduction in glyphosate-exposed oocytes. Moreover, glyphosate exposure induced the disruption of lysosome function for autophagy, showing with the decrease of LAMP2 expression and autophagy-related genes mRNA expression. Additionally, our data showed the distribution of Golgi apparatus and the functions of ribosome were disturbed after glyphosate exposure, which might affect protein synthesis and transport. Conclusions Collectively, our study showed that exposed to glyphosate could affect animal reproduction by compromising the quality of oocytes through its wide toxic effects on organelle functions.

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Section: Discussionmentioning

confidence: 77%

Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs

Chen

Wang

Pan

et al. 2022

J Animal Sci Biotechnol

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“…Melatonin has been proven to be a good protective molecule against G when co-administrated to females, with inhibition of apoptosis and autophagy, normalization of ROS levels, increased ovary weight, and the number of corpus lutea, and better viability of implanted embryos [92,112]. Another antioxidant, Dig1, has appeared as a good candidate to prevent G-mediated alterations when it was co-administrated with GBHs because it restored plasma E2 levels in vivo [64] and avoided alterations in cytochrome P450s, toxic effects, and apoptosis in in vitro human liver cell line study [113]. Vitamins C and E (antioxidants), quercetin (mitochondria-targeted flavonoid), and fulvestrant (ER antagonist) have also been tested in studies focusing on antral follicles of goats, prepubertal testes, human sperm, and human endometrial cells, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…However, higher doses of R-from 180 mg/L to 3.6 g/L-increased apoptosis, membrane degradation, and necrosis of Leydig cells, whereas G alone only impacted apoptosis and decreased cell viability [57,58]. In another study using Leydig cells from Sprague Dawley rats, 135 mg/kg/bw/d of Roundup GT plus exposure for 8 days decreased E2 but not T levels [64]. Studies on the TM3 mouse Leydig cell line exposed to G alone from 5 to 16.9 mg/L showed a great impact on the expression of steroidogenic genes, with a decrease in Cyp17a1 mRNA, Cyp11a1 mRNA, and Star mRNA and protein levels, but no effect on Hsd3b1 mRNA and protein levels [57,59].…”

Section: In Vitro Studiesmentioning

confidence: 97%

Review: Mechanisms of Glyphosate and Glyphosate-Based Herbicides Action in Female and Male Fertility in Humans and Animal Models

Serra

Estienne

Vasseur³

et al. 2021

Cells

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Glyphosate (G), also known as N-(phosphonomethyl)glycine is the declared active ingredient of glyphosate-based herbicides (GBHs) such as Roundup largely used in conventional agriculture. It is always used mixed with formulants. G acts in particular on the shikimate pathway, which exists in bacteria, for aromatic amino acids synthesis, but this pathway does not exist in vertebrates. In recent decades, researchers have shown by using various animal models that GBHs are endocrine disruptors that might alter reproductive functions. Our review describes the effects of exposure to G or GBHs on the hypothalamic–pituitary–gonadal (HPG) axis in males and females in terms of endocrine disruption, cell viability, and proliferation. Most of the main regulators of the reproductive axis (GPR54, GnRH, LH, FSH, estradiol, testosterone) are altered at all levels of the HPG axis (hypothalamus, pituitary, ovaries, testis, placenta, uterus) by exposure to GBHs which are considered more toxic than G alone due to the presence of formulants such as polyoxyethylene tallow amine (POEA).” In addition, we report intergenerational impacts of exposure to G or GBHs and, finally, we discuss different strategies to reduce the negative effects of GBHs on fertility.

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“…Several studies had previously established that TM3 cells are suitable for use in the determination of testosterone production (Ilfergane & Henkel, 2018; Jambor et al., 2019; Lin et al., 2019; Liu et al., 2016; Xia et al., 2020). However, another study demonstrated that unstimulated and stimulated TM3 cells produced a low amount of testosterone and a high amount of progesterone, suggesting that TM3 cells are unsuitable for studying the gonadal androgen biosynthesis due to altered steroidogenic pathways (Engeli, Fürstenberger, Kratschmar, & Odermatt, 2018).…”

Section: Discussionmentioning

confidence: 99%

Androgenic effect of aqueous leaf extract of Moringa oleifera on Leydig TM3 cells in vitro

et al. 2020

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Moringa oleifera (MO) is an excellent source of dietary antioxidant. MO is used traditionally to enhance libido and as an aphrodisiac in the treatment of sexual dysfunction. This study aimed to investigate the direct effect of aqueous leaf extract of MO on Leydig cell in vitro. Specifically, the effect of MO on viability, testosterone production, antioxidant activity and lipid peroxidation on TM3 cells were evaluated. TM3 cells seeded for 24 hr were exposed to aqueous leaf extract of MO (0, 10, 50, 100, 250, 500 and 1,000 µg/ml) for 24 hr, in the absence or presence of human chorionic gonadotropin (hCG; 6 mIU/200 µl). Cell viability remained unchanged while testosterone production significantly increased at 500 and 1,000 µg/ml of the extract under stimulatory conditions by 34 and 45% respectively. Glutathione level substantially increased at 250 µg/ml, while lipid peroxidation, catalase and superoxide dismutase activity, and total antioxidant capacity remained unchanged. Our results demonstrate the androgenic effect of MO especially at high concentrations in TM3 cells. The androgenic effect may be attributed to its antioxidant enzyme activities.

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The endoplasmic reticulum stress and related signal pathway mediated the glyphosate-induced testosterone synthesis inhibition in TM3 cells

Cited by 29 publications

References 39 publications

Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs

Glyphosate exposure deteriorates oocyte meiotic maturation via induction of organelle dysfunctions in pigs

Review: Mechanisms of Glyphosate and Glyphosate-Based Herbicides Action in Female and Male Fertility in Humans and Animal Models

Androgenic effect of aqueous leaf extract of Moringa oleifera on Leydig TM3 cells in vitro

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