Ovarian Dysfunction Induced by Chronic Whole‐Body PM2.5 Exposure

Zhou, Shanshan; Xi, Yueyue; Chen, Yingying; Zhang, Zezhong; Wu, Chunyan; Yan, Wei; Luo, Aiyue; Wu, Tong; Zhang, Jinjin; Wu, Meng; Dai, Jun; Shen, Wei; Zhang, Fang; Ding, Wenjun; Wang, Shixuan

doi:10.1002/smll.202000845

Cited by 59 publications

(41 citation statements)

References 64 publications

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“…The collected mouse ovaries were embedded in paraffin, and serially sectioned (5μm). As previously described [34], the ovary sections were incubated with primary antibody (anti-WIP1 (F-10) (sc-376257, 1:200, Santa Cruz Biotechnology, CA, USA; LC3B Antibody, 1:100, A19665, ABclonal, Wuhan, China; SQSTM1Antibody, 1:100, A11483, ABclonal, Wuhan, China) overnight at 4°C. The next day the ovary sections were incubated with a secondary antibody (HRP-labeled goat Anti-rabbit/mouse IgG (H+L), Servicebio, GB23204, 1:200) for 60 minutes at 37°C.…”

Section: Immunohistochemistrymentioning

confidence: 99%

“…The vaginal smears were tested at 9:00 am. every day for consecutive two weeks as previously described [35].…”

Section: Estrous Cycle Monitoring and Mating Testmentioning

confidence: 99%

“…The ovary sections harvest after two weeks' GSK2830371 treatment were stained with hematoxylin and eosin for follicle counting as previously described [35]. Briefly, every four slide was observed under the microscope and only follicles with oocytes were counted.…”

Section: Follicle Countingmentioning

confidence: 99%

“…Total protein was isolated from mouse ovaries or cultured cells for Western Blot experiments as described previously [34]. The primary antibody: Anti-WIP1 (F-10) (sc-376257 GAPDH expression was used to verify equal loading.…”

Section: Western Blotmentioning

confidence: 99%

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Regulation of Follicular Atresia by WIP1-Mediated Apoptosis and Autophagy

Zhou

Chen

et al. 2021

Preprint

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Female endocrine homeostasis and reproductive success depend on the number and quality of follicles. The follicle is the basic functional unit within mammalian ovaries. Excessive follicular atresia is responsible for the accelerated ovarian aging process. Therefore, exploring the molecular mechanism of follicle development and atresia is essential for protecting ovarian function. In this study, we interrogate the striking correlation between follicular atresia and wild-type p53-induced phosphatase 1 (WIP1) expression in mouse ovaries to understand how WIP1 phosphatase activity regulates follicle development. WIP1 is mainly expressed in granulosa cells of healthy growing follicles, and atretic follicles exhibit significantly weaker WIP1 expression compared with the healthy ones. Our in vivo study indicates that inhibition of WIP1 phosphatase activity causes endocrine disorder, fertility decline and decreased ovarian reserve by triggering excessive follicular atresia through promoting autophagy and apoptosis. By in vitro follicle culture, we determine that inhibiting the WIP1 activity impairs the follicle development, causing more follicular atresia and decreased oocyte quality. Besides, downregulating WIP1 expression in granulosa cells in vitro also promotes apoptosis and autophagy via WIP1-p53 and WIP1-mTOR signal pathway. Our findings from the in vitro and in vivo experiments revealed that appropriate Wip1 expression is required for follicle development. Downregulation of WIP1 expression accelerates follicle atresia via WIP1-p53 and WIP1-mTOR signal pathway related apoptosis and autophagy. It is speculated that moderate up-regulation of WIP1 expression may help delaying the decline of ovarian reserve.

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Section: Immunohistochemistrymentioning

confidence: 99%

“…The vaginal smears were tested at 9:00 am. every day for consecutive two weeks as previously described [35].…”

Section: Estrous Cycle Monitoring and Mating Testmentioning

confidence: 99%

Section: Follicle Countingmentioning

confidence: 99%

Section: Western Blotmentioning

confidence: 99%

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Regulation of Follicular Atresia by WIP1-Mediated Apoptosis and Autophagy

Zhou

Chen

et al. 2021

Preprint

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“…They reported that the area of the ovary containing primordial follicles was significantly decreased in mice exposed to diesel exhaust prenatally, postnatally or during both developmental periods compared to filtered air controls. Two recent publications have reported on effects of tracheal instillation of PM 2.5 [29] or inhalational exposure [30] to PM 2.5 on ovarian function. Zhou et al [30] reported an increased percentage of irregular estrous cycles and decreased primordial follicle numbers in mice after 4 months of exposure to ambient PM 2.5 compared to controls exposed to filtered air.…”

Section: Introductionmentioning

confidence: 99%

Exposure to environmentally relevant concentrations of ambient fine particulate matter (PM2.5) depletes the ovarian follicle reserve and causes sex-dependent cardiovascular changes in apolipoprotein E null mice

et al. 2022

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Background Fine particulate matter (PM2.5) exposure accelerates atherosclerosis and contains known ovotoxic chemicals. However, effects of exposure to PM2.5 on the finite ovarian follicle pool have hardly been investigated, nor have interactions between ovarian and cardiovascular effects. We hypothesized that subchronic inhalation exposure to human-relevant concentrations of PM2.5 results in destruction of ovarian follicles via apoptosis induction, as well as accelerated recruitment of primordial follicles into the growing pool. Further, we hypothesized that destruction of ovarian follicles enhances the adverse cardiovascular effects of PM2.5 in females. Results Hyperlipidemic apolipoprotein E (Apoe) null ovary-intact or ovariectomized female mice and testis-intact male mice were exposed to concentrated ambient PM2.5 or filtered air for 12 weeks, 5 days/week for 4 h/day using a versatile aerosol concentration enrichment system. Primordial, primary, and secondary ovarian follicle numbers were decreased by 45%, 40%, and 17%, respectively, in PM2.5-exposed ovary-intact mice compared to controls (P < 0.05). The percentage of primary follicles with granulosa cells positive for the mitosis marker Ki67 was increased in the ovaries from PM2.5-exposed females versus controls (P < 0.05), consistent with increased recruitment of primordial follicles into the growing pool. Exposure to PM2.5 increased the percentages of primary and secondary follicles with DNA damage, assessed by γH2AX immunostaining (P < 0.05). Exposure to PM2.5 increased the percentages of apoptotic antral follicles, determined by TUNEL and activated caspase 3 immunostaining (P < 0.05). Removal of the ovaries and PM2.5-exposure exacerbated the atherosclerotic effects of hyperlipidemia in females (P < 0.05). While there were statistically significant changes in blood pressure and heart rate variability in PM2.5-compared to Air-exposed gonad-intact males and females and ovariectomized females, the changes were not consistent between exposure years and assessment methods. Conclusions These results demonstrate that subchronic PM2.5 exposure depletes the ovarian reserve by increasing recruitment of primordial follicles into the growing pool and increasing apoptosis of growing follicles. Further, PM2.5 exposure and removal of the ovaries each increase atherosclerosis progression in Apoe-/- females. Premature loss of ovarian function is associated with increased risk of osteoporosis, cardiovascular disease and Alzheimer’s disease in women. Our results thus support possible links between PM2.5 exposure and other adverse health outcomes in women.

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Tussilagone protects acute lung injury from PM2.5 via alleviating Hif‐1α/NF‐κB‐mediated inflammatory response

Lin¹,

Chen²,

Gao³

et al. 2022

Environmental Toxicology

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Environmental pollution, especially particulate matter in the air, is a serious threat to human health. Long-term inhalation of particulate matter with a diameter < 2.5 μm (PM2.5) induced irreversible respiratory and lung injury. However, it is not clear whether temporary exposure to massive PM2.5 would result in epithelial damage and lung injury. More importantly, it is urgent to clarify the mechanisms of PM2.5 cytotoxicity and develop a defensive and therapeutic approach. In this study, we demonstrated that temporary exposure with PM2.5 induced lung epithelial cell apoptosis via promoting cytokines expression and inflammatory factors secretion. The cytotoxicity of PM2.5 could be alleviated by tussilagone (TSL), which is a natural compound isolated from the flower buds of Tussilago farfara. The mechanism study indicated that PM2.5 promoted the protein level of Hif-1α by reducing its degradation mediated by PHD2 binding, which furtherly activated NF-κB signaling and inflammatory response. Meanwhile, TSL administration facilitated the interaction of the Hif-1α/PHD2 complex and restored the Hif-1α protein level increased by PM2.5.When PHD2 was inhibited in epithelial cells, the protective function of TSL on PM2.5 cytotoxicity was attenuated and the expression of cytokines was retrieved.Expectedly, the in vivo study also suggested that temporary PM2.5 exposure led to acute lung injury. TSL treatment could effectively relieve the damage and decrease the expression of inflammatory cytokines by repressing Hif-1α level and NF-κB activation. Our findings provide a new therapeutic strategy for air pollution-related respiratory diseases, and TSL would be a potential preventive medicine for PM2.5 cytotoxicity.

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Ovarian Dysfunction Induced by Chronic Whole‐Body PM2.5 Exposure

Cited by 59 publications

References 64 publications

Regulation of Follicular Atresia by WIP1-Mediated Apoptosis and Autophagy

Regulation of Follicular Atresia by WIP1-Mediated Apoptosis and Autophagy

Exposure to environmentally relevant concentrations of ambient fine particulate matter (PM2.5) depletes the ovarian follicle reserve and causes sex-dependent cardiovascular changes in apolipoprotein E null mice

Tussilagone protects acute lung injury from PM2.5 via alleviating Hif‐1α/NF‐κB‐mediated inflammatory response

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