Ethylbenzene exposure disrupts ovarian function in Wistar rats via altering folliculogenesis and steroidogenesis-related markers and activating autophagy and apoptosis

Harrath, Abdel Halim; Alrezaki, Abdulkarem; Jalouli, Maroua; Aldawood, Nouf; Aldahmash, Waleed; Mansour, Lamjed; Alwasel, Saleh

doi:10.1016/j.ecoenv.2021.113081

Cited by 11 publications

(7 citation statements)

References 34 publications

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“…In light of these facts, follicle growth and development of the first generation have been affected, leading to a decrease in the number of growing follicles, notably secondary and tertiary follicles. This may be explained by the degenerative follicles due to the vacuolized oocytes and disorganized granulosa cells with pyknotic nuclei, similar to the results reported by many previous studies [22,50,51]. As a result, the fertility rate of the first generation significantly decreased in both the 20 and 50 mg/kg treatment groups.…”

Section: Discussionsupporting

confidence: 88%

Early Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery

Alhelaisi,

Alrezaki,

Nahdi

et al. 2023

Preprint

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Mycotoxins are produced by more than one hundred fungi and produce secondary metabolites that contaminate various agricultural commodities, especially rice and corn. Their presence in the food chain is considered a serious problem worldwide. In recent years, a link between exposure to mycotoxins and impaired fertility has been suggested. Consequently, it has become vital to investigate the interactive effects of these mycotoxins on ovarian function. In this study, we investigated the intergenerational effects of mycotoxin fumonisin B1 (FB1) on ovarian structure and function. Virgin Wistar albino female rats were separated into control and FB1 treatment groups and examined from day 6 of pregnancy until delivery (20 and 50 mg/kg/day). The obtained females of the first (F1) and second generations (F2) were euthanized at 4 weeks of age, and ovary samples were collected. We found that the ovary weight index increased with the high dose of treatment (50 mg/kg/day) among both F1 and F2, similar to that observed in polycystic ovary syndrome. As expected, FB1 at a high dose (50 mg/kg) reduced the number of primordial follicles in F1 and F2, leading to an accelerated age-related decline in reproductive capacity. Moreover, it reduced the fertility rate among F1 females by affecting follicle growth and development, as the number of secondary and tertiary follicles was decreased. Histopathological changes were evidenced by the altered structures of most of the growing follicle oocytes, as revealed by a thinning irregular zona pellucida and pyknosis in granulosa cells. These findings are concomitant with steroidogenesis- and folliculogenesis-related gene expression, as evidenced by the decrease in CYP19 activity and estrogen receptor beta (ESR2) gene expression. Additionally, GDF-9 mRNA levels significantly decreased, and IGF-1 mRNA levels significantly increased. However, the results from the ovaries of the F2 treatment groups were different and unexpected. While there was no significant variation in CYP19 compared to the control, ESR2 significantly increased, leading to stereological and histopathological changes similar to those of the control, except for some altered follicles. The hallmark histological feature was the appearance of vacuolar structures within the oocyte and between granulosa cell layers. Interestingly, the autophagic marker LC3 significantly increased in F2 offspring, whereas this protein significantly decreased in F1 offspring. Therefore, we suggest that the promotion of autophagy among the ovaries of F2 offspring may be considered a recovery mechanism from the effect of prenatal FB1 exposure. Thus, autophagy corrected the effect of FB1 during the early life of F1 females, leading to F2 offspring with ovarian structure and function similar to those of the control. However, the offspring treated females may have early ovarian aging because their ovarian pool was affected.

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Section: Discussionsupporting

confidence: 88%

Early Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery

Alhelaisi,

Alrezaki,

Nahdi

et al. 2023

Preprint

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“…Immunofluorescence analysis was performed according to the methods used in our previous studies [ 64 , 65 ]. Briefly, 3-µm-thick sections of ovarian tissues were dewaxed, hydrated with gradient ethanol and washed twice with distilled water and three times with 1x PBS.…”

Section: Methodsmentioning

confidence: 99%

Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries

Jalouli

Mofti

Elnakady

et al. 2022

IJMS

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The increased concern regarding the reduction in female fertility and the impressive numbers of women undergoing fertility treatment support the existence of environmental factors beyond inappropriate programming of developing ovaries. Among these factors are pyrethroids, which are currently some of the most commonly used pesticides worldwide. The present study was performed to investigate the developmental effects of the pyrethroid-based insecticide allethrin on ovarian function in rat offspring in adulthood. We mainly focused on the roles of oxidative stress, apoptosis, autophagy and the related pathways in ovarian injury. Thirty-day-old Wistar albino female rats were intragastrically administered 0 (control), 34.2 or 68.5 mg/kg body weight allethrin after breeding from Day 6 of pregnancy until delivery. We found that allethrin-induced ovarian histopathological damage was accompanied by elevations in oxidative stress and apoptosis. Interestingly, the number of autophagosomes in allethrin-treated ovaries was higher, and this increase was correlated with the upregulated expression of genes and proteins related to the autophagic marker LC-3. Furthermore, allethrin downregulated the expression of PI3K, AKT and mTOR in allethrin-treated ovaries compared with control ovaries. Taken together, the findings of this study suggest that exposure to the pyrethroid-based insecticide allethrin adversely affects both the follicle structure and function in rat offspring during adulthood. Specifically, allethrin can induce excessive oxidative stress and defective autophagy-related apoptosis, probably through inactivation of the PI3K/AKT/mTOR signaling pathway, and these effects may contribute to ovarian dysfunction and impaired fertility in female offspring.

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“…The immunostaining was investigated as described in our previous studies [ 70 , 71 ]. Slides containing tissue sections were placed on hotplate (60° C) and dewaxed with xylene.…”

Section: Methodsmentioning

confidence: 99%

“…The apoptotic analysis was investigated as described in our previous studies [ 35 , 70 , 72 ]. Briefly, the ovaries fixed in NBF for 24 h were preserved in 70% alcohol.…”

Section: Methodsmentioning

confidence: 99%

Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging

Aldawood

Jalouli

Alrezaki

et al. 2022

Aging

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In this study we investigated the effects of multigenerational exposures to acrylamide (ACR) on ovarian function. Fifty-day-old Wistar albino female rats were divided into the control and ACR-treated groups (2.5, 10, and 20 mg/kg/day) from day 6 of pregnancy until delivery. The obtained females of the first (AF1) and second generation (AF2) were euthanized at 4 weeks of age, and plasma and ovary samples were collected. We found that in utero multigenerational exposure to ACR reduced fertility and ovarian function in AF1 through inducing histopathological changes as evidenced by the appearance of cysts and degenerating follicles, oocyte vacuolization, and pyknosis in granulosa cells. TMR red positive cells confirmed by TUNEL assay were mostly detected in the stroma of the treated groups. Estradiol and IGF-1 concentrations significantly decreased as a result of decreased CYP19 gene and its protein expression. However, ACR exposure in AF2 led to early ovarian aging as evidenced by high estradiol and progesterone levels among all treated groups compared to control group, corresponding to the upregulation of the CYP19 gene and protein expression. The apoptotic cells of the stroma were greatly detected compared to that in the control group, whereas no significant difference was reported in ESR1 and ESR2 gene expression. This study confirms the developmental adverse effects of ACR on ovarian function and fertility in at least two consecutive generations. It emphasizes the need for more effective strategies during pregnancy, such as eating healthy foods and avoiding consumption of ACR-rich products, including fried foods and coffee.

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Ethylbenzene exposure disrupts ovarian function in Wistar rats via altering folliculogenesis and steroidogenesis-related markers and activating autophagy and apoptosis

Cited by 11 publications

References 34 publications

Early Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery

Early Life Exposure to the Mycotoxin Fumonisin B1 and Developmental Programming of the Ovary of the Offspring: The Possible Role of Autophagy in Fertility Recovery

Allethrin Promotes Apoptosis and Autophagy Associated with the Oxidative Stress-Related PI3K/AKT/mTOR Signaling Pathway in Developing Rat Ovaries

Fetal programming: in utero exposure to acrylamide leads to intergenerational disrupted ovarian function and accelerated ovarian aging

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