BIOLOGY OF REPRODUCTION
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2025
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IF 3
Jin Jing,Kou Xinhui,Wang Xinzhe,Yun Xue,Ding Yinyin,Cai Keshu,Zhai Yongning,Zhou Huifang
PurposeTo investigate how steroid receptor RNA activator (SRA) regulates follicular development in mice.MethodsSystemic SRA knockout mice were introduced. SRA expression was reinstated in the anteroventral periventricular nucleus (AVPV) of the hypothalamus using lentiviral vectors. Subsequently, the estrous cycle, serum hormone levels, follicle development, and hypothalamic kisspeptin expression in mice were assessed. Kiss1 promoter activity was tested with a fluorescent reporter system in Neuro-2a cells.ResultsSRA deficiency caused a shift to shorter metestrus and longer diestrus phases, reduced numbers of large antral and preovulatory follicles, increased formation of atretic cyst-like follicles, lowered serum levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), and decreased expression of hypothalamic AVPV-kisspeptin in mice. The reinstatement of SRA expression in the AVPV nucleus normalized kisspeptin expression, hormone levels, and follicle development. In Neuro-2a cells, SRA increased Kiss1 transcription upon E2 treatment, a response that was nullified by the estrogen receptor alpha (ERα) inhibitor.ConclusionSRA enhances ERα-mediated Kiss1 transcription in the AVPV nucleus to control the kisspeptin-GPR54 system in hypothalamus, essential for regulating ovulation through the hypothalamus-pituitary-ovary axis.
研究领域:
生殖生物学
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内分泌学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
Journal of Ovarian Research
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2024
·Vol. 17
·期 1
·1-12
·
IF 3.8
Liu Wen-Jiao,Li Li-Shu,Lan Meng-Fan,Shang Jian-Zhou,Zhang Jin-Xin,Xiong Wen-Jie,Lai Xin-Le,Duan Xing
Zinc (Zn) is a crucial trace element essential for human growth and development, particularly for reproductive health. Previous research has shown a decrease in serum zinc concentration with age and individuals with conditions such as polycystic ovary syndrome (PCOS) and diabetes mellitus. However, the specific effects of zinc deficiency on the female reproductive system, especially ovarian function, are not fully understood. In our study, we observed a significant reduction in the total number of follicles and mature follicles in the zinc deficiency group. This reduction correlated with decreased level of anti-Mullerian hormone (AMH) and abnormal gene expression affecting hormone secretion regulation. Furthermore, we found that zinc deficiency disrupted mitochondrial dynamics, leading to oxidative stress in the ovaries, which further inhibited autophagy and increased ovarian apoptosis. These changes ultimately resulted in the failure of germinal vesicle breakdown (GVBD) and reduced oocyte quality. Meanwhile, administration of zinc glycine effectively alleviated the oocyte meiotic arrest caused by dietary zinc deficiency. In conclusion, our findings demonstrated that dietary zinc deficiency can affect hormone secretion and follicle maturation by impairing mitochondrial function and autophagy.
研究领域:
生殖生物学
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营养学
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内分泌学
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DOI
高影响因子
EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY
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2017
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IF 1.975
Ting Zhang,Ying Chen,Yang Yang,Zhonghui Wang,Qi Pan,Sichong Xu,Zuyue Sun
The purpose of this study is to identify the potential of a two-dimensional preantral follicle culture as an in vitro model of predicting premature ovarian failure . The two-dimensional preantral follicles culture method was established by cultivating preantral follicles collected from ICR F1 hybrids (aged 12–14 days) for 12 days. The preantral follicles were incubated with 0.54 mg/ml cyclophosphamide , 0.5 mg/ml busulfan , 0.12 mg/ml cisplatin , 3.12 mg/ml 4-vinylcyclohexene diepoxide, 5 mg/ml D (+) galactose , and 0.5 mg/ml hydrocortisone for 24 h at culture days 2, 6 and 11. The diameter of follicles, the cumulus-oocyte complex number and the maturity of oocytes were recorded as the parameters to detect follicular maturation induced by the culture agents. The results indicated that, except for busulfan, D (+) galactose, and hydrocortisone, such test articles could significantly decrease follicular growth ( p < 0.05 or p < 0.01), and induce oocyte degeneration and follicle atresia when the follicles were treated at day 2. With the exception of hydrocortisone, such agents also gradually decreased follicular development ( p < 0.05 or p < 0.01) when the follicles were treated at day 6. All of the test articles but hydrocortisone can interfere with the ovulation , the cumulus-oocyte complex discharge and oocyte maturation of follicles when treated at days 2, 6 and 11. It is suggested that two-dimensional preantral follicle culture could be utilized as a potential in vitro system to mimic the POF model. It may also be employed in screening potential ovarian toxic agents, reducing laboratory animal use and promoting animal welfare .
研究领域:
生殖生物学
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毒理学
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动物模型
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产品关联
DOI
PubMed
高影响因子
REPRODUCTIVE TOXICOLOGY
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2024
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IF 3.3
Luyao Yang,Shuangshuang Wang,Jing Jin,Jiahui Wang,Wenyue Chen,Yun Xue,Liang Sheng,Yongning Zhai,Weifeng Yao
Sucralose, the extensively utilized sweetener, might lead to metabolic disorders with prolonged consumption, but it remains uncertain if sucralose has any impact on female reproductive health. We incorporated sucralose into drinking water and observed food intake, body weight, estrous cycle, follicular development, serum hormones, and insulin sensitivity of mice. The mice did not experience any changes in their food intake or body weight after consuming sucralose. However, they displayed irregularities in the estrous cycle, marked by a reduced count of primordial, primary, and secondary follicles, coupled with a significant increase in the number of antral follicles. There was a decline in follicle-stimulating hormone (FSH), estradiol (E2), and progesterone (P4) levels, while testosterone (T) and luteinizing hormone (LH) levels surged, leading to a notable elevation in the LH / FSH ratio. Sucralose also induced insulin resistance, as evidenced by elevated insulin levels and impaired insulin tolerance, which responded to an increase in bacterial-derived serum endotoxin. By eliminating insulin resistance with rosiglitazone (RSG), eradicating intestinal flora-derived endotoxins with neomycin (NEO), or enhancing intestinal barrier function with indole-3-carbinol (I3C), the abnormalities in estrous cycle, disruptions in follicular development, hormonal imbalances and elevation in serum endotoxins induced by sucralose were successfully reversed. The present study indicates that sucralose-induced follicular dysplasia in mice is probably related to impaired intestinal permeability, infiltration of endotoxins, initiation of systemic inflammation, and insulin resistance.
研究领域:
生殖生物学
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内分泌学
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微生物学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY LETTERS
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2019
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IF 3.499
Yiwei Guo,Wenxiang Wang,Yiqin Chen,Yan Sun,Yuchen Li,Fangyuan Guan,Qi Shen,Yiruo Guo,Wenchang Zhang
Information on the effects of gibberellic acid (gibberellin A3, GA3) on ovarian follicle development is limited. In our present study, 21-day-old female Wistar rats were exposed to GA3 by gavage (25, 50, and 100 mg/kg body weight, once per day) for eight weeks to evaluate the influence of GA3 on ovarian follicle development. After treatment, significant (P < 0.05) increases (to 40.17 % and 44.5 %, respectively) in atretic follicle proportions and significant decreases (to 19.49 % and 17.86 %, respectively) in corpus luteum proportions were observed in the 50 and 100 mg/kg treatment groups compared to the control group. Significant (P < 0.05) increases (to 31.3 % and 42.0 %, respectively) in follicle apoptosis were observed in the 50 and 100 mg/kg treatment groups by transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assays. Significantly increased expression of caspase-3, caspase-8, caspase-9 and Fas was observed by real-time PCR and Western blotting. Bisulfite sequencing PCR (BSP) revealed obviously decreased total methylation percentages of the caspase-3 promoter region in the two treatment groups. Real-time quantitative PCR also showed significantly decreased mRNA expression of DNA methyltransferase (Dnmt) 3a and Dnmt3b. Further in vitro studies showed that a DNA methylation inhibitor could enhance the GA3-induced increase in the mRNA expression of caspase-3. Overall, our present study indicates that GA3 administration from weaning until sexual maturity can affect ovarian follicle development by inducing apoptosis and suggests that signaling through the Fas-mediated apoptotic pathway may be an important underlying mechanism of this apoptosis. In addition, GA3-induced aberrant DNA methylation patterns might be partly responsible for upregulation of caspase-3 gene expression.
研究领域:
生殖生物学
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分子生物学
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表观遗传学
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DOI
PubMed
高影响因子
Genes
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2022
·Vol. 13
·期 7
·1113
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IF 4.141
Biying Jiang,Baolong Cao,Zhichun Zhou,Zejiao Li,Can Lv,Jiannan Zhang,Heyuan Zhang,Yajun Wang,Juan Li
Adrenoceptors are suggested to mediate the functions of norepinephrine (NE) and epinephrine (EPI) in the central nervous system (CNS) and peripheral tissues in vertebrates. Compared to mammals, the functionality and expression of adrenoceptors have not been well characterized in birds. Here, we reported the structure, expression, and functionality of chicken functional α2A-adrenoceptor, namedADRA2A. The cloned chickenADRA2AcDNA is 1335 bp in length, encoding the receptor with 444 amino acids (a.a.), which shows high amino acid sequence identity (63.4%) with its corresponding ortholog in humans. Using cell-based luciferase reporter assays and Western blot, we demonstrated that the ADRA2A could be activated by both NE and EPI through multiple signaling pathways, including MAPK/ERK signaling cascade. In addition, the mRNA expression ofADRA2Ais found to be expressed abundantly in adult chicken tissues including thyroid, lung, ovary and adipose from the reported RNA-Seq data sets. Moreover, the mRNA expression ofADRA2Ais also found to be highly expressed in the granulosa cells of 6–8 mm and F5 chicken ovarian follicles, which thus supports that ADRA2A signaling may play a role in ovarian follicular growth and differentiation. Taken together, our data provide the first proof that the α2A-adrenoceptor is functional in birds involving avian ovarian follicular development.Keywords:chickens;α2-adrenoceptor;ADRA2A
研究领域:
分子生物学
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内分泌学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
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2023
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IF 4.4
Manman Shen,Tao Li,Yuan Feng,Ping Wu,Boris Ramos Serrano,Adileidys Ruiz Barcenas,Liang Qu,Weiguo Zhao
ABSTRACT Quercetin ( Que ), widely found in a huge variety of plants, plays important roles in ovarian function. However, to data, there have been no reports about Que regulating granulosa cells ( GCs ) in prehierarchical follicles in chicken. Herein, GCs from follicles diameter from 4 to 8 mm in chicken were treated by Que in vitro culture to investigate how Que exerts its effect on follicular development. GCs treated by Que in concentrations of 10, 100, and 1,000 ng/mL were tested for cell proliferation and progesterone secretion. Eight cDNA libraries were constructed from GCs (4 samples per group) to explore transcriptome expression changes. The role of the MAPK/ERK signaling pathway was validated in this process. Treatment with 100 and 1,000 ng/mL levels of Que significantly promoted cell proliferation and progesterone secretion ( P < 0.05). RNA-seq analysis data showed that 402 and 263 differentially expressed genes ( DEGs ) were up- and down-regulated, respectively. Functional enrichment analysis that the pathways related to follicular development included biosynthesis of amino acids, MAPK signaling pathway, and calcium signaling pathway. Notably, the function exerted in GCs of the different levels of Que was associated with the suppression of the MAPK pathway. In conclusion, our results proved that low levels of Que could promote MAPK signaling pathway, but high levels of Que inhibit MAPK signaling pathway in GCs from the prehierarchical follicles, promote cell proliferation and progesterone secretion, and benefit follicle selection.
研究领域:
动物科学
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分子生物学
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生殖生物学
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产品关联
DOI
PubMed
高影响因子
CELL BIOCHEMISTRY AND FUNCTION
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2024
·Vol. 42
·期 8
·e70015
·
IF 2.8
Yang Yu,Tianchan Zhang,Xin Li,Tianyang Yu,Fanci Meng,Yifeng Luan,Huifang Cong,Xiuhong Wu
Perimenopausal syndrome is a significant issue that disturbs women's metabolism, mood and quality of life. Apigenin (4′,5,7-trihydroxyflavone) is a natural flavonoid that exhibits antioxidant, anti-inflammatory and anticancer effects. The present study aims to investigate the effect of apigenin on perimenopausal syndrome by combining bioinformatics analysis with in vivo experiments. The mouse model with perimenopausal syndrome was established using 4-vinylcyclohexene diepoxide (VCD) treatment. Apigenin alleviated VCD-induced disorder of estrous cycle and shrinkage of ovarian tissue. The reduction of anti-Muller hormone and the increase of follicle stimulation hormone and luteinizing hormone triggered by VCD were reversed by apigenin in a dose-dependent manner. Apigenin suppressed the VCD-induced decrease of primordial, primary, secondary and antral follicle number in ovarian tissue. Oxidative stress in ovarian tissue was activated by VCD treatment through increasing the reactive oxygen species production. High concentration of apigenin significantly reversed the alteration induced by VCD. Apigenin alleviated VCD-induced cell apoptosis through regulating Bax, Bcl-2, cleaved PARP1 and caspase-3. Furthermore, the phosphorylation of AKT and FOXO3a was inhibited by VCD and activated by apigenin in a dose-dependent manner. Collectively, apigenin effectively mitigates the ovarian dysfunction through suppressing oxidative stress and apoptosis via the AKT/FOXO3a signaling pathway. Summary Perimenopausal syndrome characterized by endocrine disorders, and hormone disorders has caused physical and mental damage to the majority of women. This study aims to explore a safe and effective method for perimenopausal syndrome treatment. Apigenin is a natural flavonoid that has protective effects on ovary, while the effect and mechanism of apigenin on perimenopausal syndrome is still unclear. This study's principal finding was that apigenin alleviated the estrous cycle disorder, follicle development inhibition and hormone level disorder in model with perimenopausal syndrome. Additionally, apigenin suppressed oxidative stress and apoptosis via activating the AKT/FOXO3a signaling pathway in the ovarian tissue of perimenopausal mice model. This work provides an effective approach for the remission and treatment of perimenopausal syndrome.
研究领域:
药理学
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内分泌学
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妇科学
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生物信息学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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