Molecular and Cellular Endocrinology最新文献_第4页

Dietary advanced glycation end products (AGEs) and superovulation with gonadotropins alter RAGE expression in the ovaries differently at each follicular stage of development 膳食中的高级糖化终产物和促性腺激素超排卵会改变卵泡发育各阶段卵巢中的 RAGE 表达。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-25 DOI: 10.1016/j.mce.2025.112482

Zaher Merhi , Michelle Goldsammler , Maureen J. Charron , Erkan Buyuk

The purpose of this study was to examine the deposition of advanced glycation end products (AGEs) and their receptors, RAGE, in ovarian follicles during folliculogenesis in mice fed high (H-AGE) or low (L-AGE) AGE diets and following superovulation with gonadotropins. We hypothesize that H-AGE diet is associated with increased AGE deposition and RAGE expression in various stages of ovarian follicular development, and superovulation with gonadotropins may alter these changes. C57BL/6J mice were fed low L-AGE (n = 10) or H-AGE (n = 10) diet for 12 weeks. In each group, half of each cohort (n = 5) were sacrificed at the end of 12 weeks while the other half (n = 5) were superovulated prior to sacrifice. Immunofluorescence staining of ovarian sections was used to determine AGE deposition and RAGE expression in ovarian follicles in a semi-quantitative manner. In all mice, AGE deposition and RAGE expression were observed in granulosa but not theca cells. In all mice, AGE deposition intensity increased as the follicles progressed through developmental stages from primordial to primary to secondary to prenatral/antral but then significantly dropped in the corpus luteum stage. RAGE staining was highly expressed equally in all stages of pre-ovulatory follicles but then significantly dropped in the corpus luteum post-ovulatory stage. Compared to mice on L-AGE diet, mice on H-AGE mice had significantly lower AGE deposition in their primordial follicles and lower RAGE intensity in their antral follicles. Following superovulation, mice in both groups had significantly lower AGE deposition and significantly lower RAGE expression but the drop in AGE deposition following superovulation was more pronounced in the H-AGE diet group compared to the L-AGE diet group in both pre-ovulatory and post-ovulatory follicles. Ovarian AGE deposition and RAGE expression changes differently during the natural follicular development. Opposite to expectations, the intake of diet rich in AGEs caused lower expression of the proinflammatroy RAGE, an effect that was more pronounced after gonadotropin exposure.

本研究的目的是检测喂食高（H-AGE）或低（L-AGE）AGE饮食并使用促性腺激素超排卵的小鼠在卵泡生成过程中高级糖化终产物（AGE）及其受体 RAGE 在卵泡中的沉积情况。我们推测，H-AGE饮食与卵泡发育各阶段AGE沉积和RAGE表达的增加有关，而促性腺激素超排卵可能会改变这些变化。用低L-AGE（10只）或H-AGE（10只）饮食喂养C57BL/6J小鼠12周。每组中有一半（n=5）在12周结束时被处死，另一半（n=5）在处死前接受超排卵。对卵巢切片进行免疫荧光染色，以半定量的方式确定卵巢滤泡中的 AGE 沉积和 RAGE 表达。在所有小鼠的颗粒细胞中都观察到了 AGE 沉积和 RAGE 表达，而在卵巢细胞中没有观察到。在所有小鼠中，AGE沉积强度随着卵泡发育阶段（从原始卵泡到初级卵泡到次级卵泡到产前/产后卵泡）的进展而增加，但在黄体阶段显著下降。RAGE染色在排卵前卵泡的所有阶段都同样高度表达，但在排卵后黄体阶段则显著下降。与食用L-AGE饲料的小鼠相比，食用H-AGE饲料的小鼠原始卵泡中的AGE沉积明显较低，前卵泡中的RAGE强度也较低。超排卵后，两组小鼠的 AGE 沉积和 RAGE 表达均明显降低，但与 L-AGE 饮食组相比，H-AGE 饮食组小鼠超排卵后在排卵前和排卵后卵泡中的 AGE 沉积下降更为明显。在自然卵泡发育过程中，卵巢 AGE 沉积和 RAGE 表达发生了不同的变化。与预期相反，摄入富含 AGEs 的饮食会降低促炎症 RAGE 的表达，这种效应在促性腺激素暴露后更为明显。

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引用次数: 0

Bisphenol A-induced cancer-associated adipocytes promotes breast carcinogenesis via CXCL12/AKT signaling

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-24 DOI: 10.1016/j.mce.2025.112473

Zhiyuan Dong , Liping He , Jinyi Wu , Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li

Bisphenol A (BPA), a commonly used plastic additive, is believed to cause obesity. As an environmental endocrine disruptor, BPA is closely associated with the onset and progression of BC. However, the molecular mechanisms underlying the promotion of breast cancer by BPA remain unclear. As obesity is a significant risk factor for breast cancer, this study aimed at exploring whether BPA facilitates the progression of breast cancer by inducing obesity. Using the National Health and Nutrition Examination Survey data, a positive correlation was observed between BPA exposure and the risk of sex-specific cancers among US adults with body mass index ≥30, suggesting that obesity may be influenced by urinary BPA. 3T3-L1 cells differentiated into mature adipocytes following treatment with 10⁻⁸ M BPA, and subsequent treatment with 4T1-conditioned medium acquired properties associated with cancer-associated adipocytes (CAAs). Network pharmacology suggested that CXCL12 may serve as a key target gene in breast cancer progression. Follow-up PCR analysis revealed high CXCL12 expression in BPA-induced CAAs. Overexpression of CXCL12 promoted epithelial-mesenchymal transition (EMT) and 4T1 cell migration by activating the AKT pathway. In vivo, BPA-induced CAAs accelerated tumor growth compared to a controls xenografted with only 4T1 cells. In tissues from the BPA-CAAs group, the expression of CXCL12, markers associated with CAAs, phosphorylated AKT, N-cadherin, and vimentin was markedly elevated, whereas the expression of E-cadherin was reduced. In conclusion, BPA may induce adipose cells to differentiate into CAA-like cells and subsequently advance breast cancer EMT through the CXCL12/AKT pathway.

{"title":"Bisphenol A-induced cancer-associated adipocytes promotes breast carcinogenesis via CXCL12/AKT signaling","authors":"Zhiyuan Dong , Liping He , Jinyi Wu , Chunfeng Xie, Shanshan Geng, Jieshu Wu, Caiyun Zhong, Xiaoting Li","doi":"10.1016/j.mce.2025.112473","DOIUrl":"10.1016/j.mce.2025.112473","url":null,"abstract":"<div><div>Bisphenol A (BPA), a commonly used plastic additive, is believed to cause obesity. As an environmental endocrine disruptor, BPA is closely associated with the onset and progression of BC. However, the molecular mechanisms underlying the promotion of breast cancer by BPA remain unclear. As obesity is a significant risk factor for breast cancer, this study aimed at exploring whether BPA facilitates the progression of breast cancer by inducing obesity. Using the National Health and Nutrition Examination Survey data, a positive correlation was observed between BPA exposure and the risk of sex-specific cancers among US adults with body mass index ≥30, suggesting that obesity may be influenced by urinary BPA. 3T3-L1 cells differentiated into mature adipocytes following treatment with 10<sup>−8</sup> M BPA, and subsequent treatment with 4T1-conditioned medium acquired properties associated with cancer-associated adipocytes (CAAs). Network pharmacology suggested that CXCL12 may serve as a key target gene in breast cancer progression. Follow-up PCR analysis revealed high CXCL12 expression in BPA-induced CAAs. Overexpression of CXCL12 promoted epithelial-mesenchymal transition (EMT) and 4T1 cell migration by activating the AKT pathway. <em>In vivo</em>, BPA-induced CAAs accelerated tumor growth compared to a controls xenografted with only 4T1 cells. In tissues from the BPA-CAAs group, the expression of CXCL12, markers associated with CAAs, phosphorylated AKT, N-cadherin, and vimentin was markedly elevated, whereas the expression of E-cadherin was reduced. In conclusion, BPA may induce adipose cells to differentiate into CAA-like cells and subsequently advance breast cancer EMT through the CXCL12/AKT pathway.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112473"},"PeriodicalIF":3.8,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Chemerin mediates exercise-induced improvements of bone microstructure and bone mass in diabetes or high fat diet mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-24 DOI: 10.1016/j.mce.2025.112471

Xiaohan Yu , Xinyan Pan , Mei Huang , Xiaoye Lin , Xiaohui Wang

To clarify the roles and mechanisms of adipokine chemerin in exercise-induced bone improvements in type 2 diabetes mellitus (DM) mice and mice fed on high fat diet (HFD). DM mice were established by HFD + streptozotocin injection, exogenous chemerin was supplemented prior to running, and found that exogenous chemerin reversed 6-week exercise-induced improvements in cancellous bone parameters in DM mice. While adipose-specific chemerin knockout improved microstructure and mass of cancellous bone in HFD mice and further increased exercise-induced bone improvements, accompanied with promoted osteogenesis and inhibited osteoclasis represented as the changes of RANKL, M-CSF, Runx2, Osterix, OPG, ALP and CTSK. These results indicated that reduced chemerin contributed to exercise-induced enhancements in the microstructure and mass of cancellous bone in DM and HFD mice in association with osteogenesis promotion and osteoclasis inhibition, which is beneficial to clarify chemerin's impact on bone remodeling in metabolic diseases at sedentary and exercise states.

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引用次数: 0

Endocrine Disruptors Chemicals: Impacts of Bisphenol A, Tributyltin and Lead on Thyroid Function

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-22 DOI: 10.1016/j.mce.2025.112467

Glaecir Roseni Mundstock Dias , Andrea Claudia Freitas Ferreira , Leandro Miranda-Alves , Jones Bernardes Graceli , Denise Pires de Carvalho

The large-scale industrial production characteristic of the last century led to an increase in man-made compounds and mobilization of natural compounds, many of which can accumulate in the environment and organisms due to their bioaccumulation and biomagnification properties. The endocrine system is especially vulnerable to these compounds that are known as endocrine disruptor chemicals (EDCs). Thyroid hormones (THs) are essential for normal development and growth, besides being the main regulators of basal metabolic rate. Thus, compounds able to affect THs synthesis, transport, and action could produce important deleterious effects, impacting the development of metabolic and endocrine diseases. Herein, we will review the main effects of EDCs on the thyroid axis, with special emphasis on the widely used substances bisphenol A (BPA), employed in the synthesis of polycarbonate plastics and epoxy resins; tributyltin (TBT), an organotin chemical substance widely used in several agro-industrial applications; and lead (Pb), a ubiquitous environmental and occupational polluting heavy metal. Exposure to these EDCs occurs mainly from the ingestion of contaminated food and beverages. Furthermore, there are few epidemiological studies evaluating human risk, and experimental studies employ different exposure models, making it difficult to integrate results. However, even low doses of these EDCs warn of thyrotoxicity. Since THs homeostasis is essential for health and humans are increasingly being exposed to EDCs, it is important to clarify which substances might act as thyroid hormone system disrupting chemicals and how they act in order to try to overcome their deleterious effects and limit the exposure to these compounds.

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引用次数: 0

Vagotomy suppresses food intake by increasing GLP-1 secretion via the M3 AChR-AMPKα pathway in mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112464

Jie Lin , Yikai Shen , Yiwen Xia , Ying Li , Tianlu Jiang , Xusheng Shen , Yiwang Fu , Diancai Zhang , Li Yang , Hao Xu , Zekuan Xu , Linjun Wang

Objective

The gut-brain axis (GBA) is involved in the modulation of multiple physiological activities, and the vagus nerve plays an important role in this process. However, the association between vagus nerve function and nutritional regulation remains unclear. Here, we explored changes in the nutritional status of mice after vagotomy and investigated the underlying mechanisms responsible for these changes.

Methods

We performed vagotomies in mice and verified nerve resection using immunofluorescence staining. We then observed the food intake and body weight of the mice and tested nutritional and inflammation-related markers using enzyme-linked immunosorbent assay (ELISA) kits. The role of glucagon-like peptide 1 (GLP-1) in the GBA was determined using qRT-PCR and ELISA kits. Western blot and ELISA kits were used to explore the underlying mechanisms.

Results

After vagotomy, the mice experienced a deterioration in their nutritional status, which manifested as a significant reduction in body weight and food intake. The expression of the proglucagon gene (GCG), which encodes GLP-1, significantly increased after vagotomy. Mechanistically, acetylcholine (ACh) reversed the HG (high glucose) -induced elevation of GLP-1 secretion. ACh upregulated AMPKα phosphorylation, thereby reducing GLP-1 secretion. Moreover, the level of AMPKα phosphorylation was enhanced by ACh via M3AChR.

Conclusions

ACh released by the vagus nerve counteracts the anorectic effects of GLP-1 under normal physiological conditions. Vagotomy blocks this feedback, resulting in a loss of food intake and body weight in mice.

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引用次数: 0

Loss of chemerin prevents ovariectomy-induced osteoporosis in mice through intraosseous vascular remodeling

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112465

Bingjie Wang , Jinghuai Ni , Lingling Yu , Shuai Chen , Wenbin Shang , Penghua Fang , Wen Min

Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2^−/−) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2^−/− mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2^−/− mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2^−/− mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2^−/− mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.

{"title":"Loss of chemerin prevents ovariectomy-induced osteoporosis in mice through intraosseous vascular remodeling","authors":"Bingjie Wang , Jinghuai Ni , Lingling Yu , Shuai Chen , Wenbin Shang , Penghua Fang , Wen Min","doi":"10.1016/j.mce.2025.112465","DOIUrl":"10.1016/j.mce.2025.112465","url":null,"abstract":"<div><div>Chemerin, an adipocyte-secreted adipokine, can regulate bone resorption and bone formation and is a promising therapy for postmenopausal osteoporosis. However, the effect of endogenous chemerin on intraosseous vascular remodeling in postmenopausal osteoporosis remains unclear. In this study, we investigated the effect of chemerin on osteogenesis formation and intraosseous vascular remodeling in ovariectomized Rarres2 knockout (Rarres2<sup>−/−</sup>) mice. The results showed that the bone mineral density (BMD) and volume score, trabecular thickness, cortical thickness, bone formation marker BALP and osteocalcin, and angiogenesis markers CD31 and EMCN significantly increased in ovariectomized Rarres2<sup>−/−</sup> mice. Furthermore, the expression of biomarkers to osteoblasts (β-catenin and Runx2) and angiogenesis markers (VEGF-A, Noggin, and Ang-1) significantly increased in the bone tissue of ovariectomized Rarres2<sup>−/−</sup> mice, as well as in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2<sup>−/−</sup> mice. Conversely, treatment with chemerin significantly inhibited expression of biomarkers for osteoblasts and angiogenesis markers in bone marrow stromal cells and primary intraosseous vascular endothelial cells of Rarres2<sup>−/−</sup> mice. More importantly, the supernatants of the primary intraosseous vascular endothelial cells of the Rarres2<sup>−/−</sup> mice could promote the osteogenic differentiation effect of BMSCs, which could be blocked by treating with the chemerin recombinant protein. These data indicate that endogenous chemerin has an inhibitory effect on intraosseous vascular formation as well as osteoblast differentiation and proliferation in ovariectomy-induced osteoporosis mice. Chemerin effectively promoted postmenopausal osteoporosis development, which is associated with the involvement of chemerin in the reduction of microcirculation within the skeleton.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"599 ","pages":"Article 112465"},"PeriodicalIF":3.8,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Skeletal muscle disorders as risk factors for type 2 diabetes

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-21 DOI: 10.1016/j.mce.2025.112466

Eshwar R. Tammineni , Carlo Manno , Goldie Oza , Lourdes Figueroa

The incidence and prevalence of muscular disorders and of type 2 diabetes (T2D) is increasing and both represent highly significant healthcare problems, both economically and compromising quality of life. Interestingly, skeletal muscle dysfunction and T2D share some commonalities including dysregulated glucose homeostasis, increased oxidative stress, dyslipidemia, and cytokine alterations. Several lines of evidence have hinted to a relationship between skeletal muscle dysfunction and T2D. For instance, T2D affects skeletal muscle morphology, functionality, and overall health through altered protein metabolism, impaired mitochondrial function, and ultimately cell viability. Conversely, humans suffering from myopathies and their experimental models demonstrated increased incidence of T2D through altered muscle glucose disposal function due to abnormal calcium homeostasis, compromised mitochondrial function, dyslipidemia, increased inflammatory cytokines and fiber size alterations and disproportions. Lifestyle modifications are essential for improving and maintaining mobility and metabolic health in individuals suffering from myopathies along with T2D. In this review, we updated current literature evidence on clinical incidence of T2D in inflammatory, mitochondrial, metabolic myopathies, and muscular dystrophies and further discussed the molecular basis of these skeletal muscle disorders leading to T2D.

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引用次数: 0

Identification of puberty related miRNAs in the hypothalamus of female mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-20 DOI: 10.1016/j.mce.2025.112468

Pavlos Fanis , Maria Morrou , Marios Tomazou , Hend Abdulgadr M. Alghol , George M. Spyrou , Vassos Neocleous , Leonidas A. Phylactou

Background and aims

Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty.

Methods

Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis.

Results

Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation.

Conclusion

The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.

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引用次数: 0

The impact of obesity on mitochondrial dysfunction during pregnancy 肥胖对妊娠期线粒体功能障碍的影响。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-18 DOI: 10.1016/j.mce.2025.112463

Mariana Pacheco de Oliveira, Larissa Espindola da Silva, Bruna Barros Fernandes, Mariella Reinol Steiner, Debora Gehrke Pistóia, Tamires dos Santos Cichella, Luana Bahia Jacinto, Karoline Marcondes Spuldaro, Betine Pinto Moehlecke Iser, Gislaine Tezza Rezin

Mitochondria play a central role in nutrient metabolism, besides being responsible for the production of adenosine triphosphate (ATP), the main source of cellular energy. However, the ATP production process is associated with the generation of reactive oxygen species (ROS), which excessive accumulation can cause mitochondrial dysfunction. This dysfunction, in turn, causes the accumulation of fatty acids in the adipose tissue, triggering a local inflammatory process that can evolve into systemic inflammation. In women with obesity, an increase in lipid levels in the placental environment is observed. The high presence of fatty acids compromises the structural integrity and mitochondrial membrane, culminating in the release of ROS. This process damages the DNA of placental cells and causes an inflammatory state, affecting metabolic efficiency. This vicious cycle is characterized by defects in mitochondrial ATP production, which can lead to lipid accumulation and inflammation. In pregnant women with obesity, these mitochondrial changes play a determining role in pregnancy outcomes. Hence, the objective of this study was to search the literature to review the impact of mitochondrial dysfunction in the maternal obesity.

线粒体除了负责产生三磷酸腺苷（ATP）（细胞能量的主要来源）外，还在营养代谢中起着核心作用。然而，ATP的产生过程与活性氧（ROS）的产生有关，活性氧的过度积累会导致线粒体功能障碍。反过来，这种功能障碍导致脂肪酸在脂肪组织中积累，引发局部炎症过程，进而演变成全身性炎症。在肥胖妇女中，观察到胎盘环境中脂质水平的增加。脂肪酸的大量存在损害了结构完整性和线粒体膜，最终导致ROS的释放。这个过程会破坏胎盘细胞的DNA，导致炎症状态，影响代谢效率。这种恶性循环的特点是线粒体ATP产生缺陷，从而导致脂质积累和炎症。在肥胖孕妇中，这些线粒体变化在妊娠结局中起着决定性作用。因此，本研究的目的是通过文献检索来回顾线粒体功能障碍对产妇肥胖的影响。

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引用次数: 0

GSTA2 overexpression alleviates bis (2-ethylhexyl) phthalate (DEHP)-induced male reproductive disorders by inhibiting oxidative stress-mediated cell apoptosis via the activated PI3K/AKT signaling pathway GSTA2过表达通过激活PI3K/AKT信号通路抑制氧化应激介导的细胞凋亡，减轻邻苯二甲酸二酯（2-乙基己基）（DEHP）诱导的男性生殖障碍。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-01-17 DOI: 10.1016/j.mce.2025.112462

Lei Wei , Zonggang Feng , Qian Dou , Genhong Mao , Hu Zhao , Xinghua Zhao , Bin Hao

Male reproductive disorders are responsible for approximately 50% of infertility cases. Bis (2-ethylhexyl) phthalate (DEHP) is a common environmental pollutant known for its reproductive toxicity. Oxidative stress is a key mechanism in response to DEHP exposure. Glutathione S-transferase A2 (GSTA2), a member of the glutathione S-transferase family, has the capacity to detoxify environmental toxins. However, its role in regulating DEHP-induced male reproductive disorders remains unexplored. Next, male mice aged 3 weeks were orally administered with DEHP (500 mg/kg/day) for 14 days to induce male reproductive disorders. We observed a decrease in the GSTA2 expression in the testicular tissues of DEHP-treated mice. To investigate the role of GSTA2 in DEHP exposure, lentiviral vectors carrying GSTA2 sequences (1 × 10⁷ TU/mL, 20 μL) were given to mice on the first day of DEHP treatment. GSTA2 overexpression was found to alleviate testicular damage induced by DEHP, as well as to inhibit oxidative stress and subsequent cell apoptosis. In addition, the PI3K/AKT signaling pathway, which is associated with oxidative stress and DEHP exposure, was activated in DEHP-exposed mice following GSTA2 overexpression. Subsequently, mouse spermatocyte GC-2spd cells with DEHP treatment were used to mimic male reproductive disorders in vitro. Consistently, the GSTA2 expression was decreased in GC-2spd cells with DEHP treatment. GSTA2 overexpression inhibited oxidative stress and cell apoptosis in DEHP-treated GC-2spd cells by activating the PI3K/AKT signaling pathway. Moreover, we discovered that GSTA2 overexpression significantly altered the metabolic profiles of DEHP-treated GC-2spd cells. Collectively, our results suggest that GSTA2 overexpression alleviates DEHP-induced male reproductive disorders by suppressing oxidative stress-mediated cell apoptosis via the PI3K/AKT signaling pathway, providing a novel insight into mitigating reproductive toxicity caused by DEHP exposure.

男性生殖障碍导致大约50%的不孕症病例。邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种常见的环境污染物，具有生殖毒性。氧化应激是DEHP暴露反应的关键机制。谷胱甘肽s -转移酶A2 （GSTA2）是谷胱甘肽s -转移酶家族的一员，具有解毒环境毒素的能力。然而，其在调节dehp诱导的男性生殖障碍中的作用仍未被探索。然后，给3周龄雄性小鼠口服DEHP （500 mg/kg/天），连续14天诱导雄性生殖障碍。我们观察到dehp处理小鼠睾丸组织中GSTA2表达降低。为了研究GSTA2在DEHP暴露中的作用，在DEHP治疗的第一天，将携带GSTA2序列（1 × 107 TU/mL, 20 μL）的慢病毒载体给予小鼠。GSTA2过表达可减轻DEHP引起的睾丸损伤，并抑制氧化应激和随后的细胞凋亡。此外，GSTA2过表达后，与氧化应激和DEHP暴露相关的PI3K/AKT信号通路在DEHP暴露小鼠中被激活。随后，使用DEHP处理的小鼠精细胞GC-2spd细胞在体外模拟男性生殖障碍。DEHP处理后，GC-2spd细胞中GSTA2表达下降。GSTA2过表达通过激活PI3K/AKT信号通路抑制dehp处理的GC-2spd细胞的氧化应激和细胞凋亡。此外，我们发现GSTA2过表达显著改变了dehp处理的GC-2spd细胞的代谢谱。总之，我们的研究结果表明，GSTA2过表达通过PI3K/AKT信号通路抑制氧化应激介导的细胞凋亡，从而减轻DEHP诱导的男性生殖障碍，为减轻DEHP暴露引起的生殖毒性提供了新的见解。

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引用次数: 0