Rapamycin preserves the primordial follicle pool during cisplatin treatment in vitro and in vivo.

Abstract:
:Rapamycin has been proven to effectively inhibit the activation of primordial follicles while cisplatin-induced the loss of primordial follicles due to the over-activation of the primordial follicle stockpile. Whether rapamycin could inhibit the loss of primordial follicles induced by cisplatin is still unknown. The ovaries of neonatal Sprague Dawley rats were cultured in vitro in different doses of rapamycin (0.08, 0.16, and 0.32 μg/ml) and cisplatin (0.1, 0.4, and 0.8 μg/ml). The immature BALB/c mice were administered cisplatin with or without rapamycin by intraperitoneal injection. Ovaries were collected to analyze the histomorphology, the messenger RNA (mRNA) expression of anti-Mullerian hormone (AMH), growth differentiation factor 9 (GDF9), and bone morphogenetic protein 15 (BMP15) and the expression of key proteins of mammalian target of rapamycin (mTOR) pathway. Growing follicle counts of ovaries cultured in vitro in the R0.16 and R0.32 groups were decreased and the ratio of growing to primordial follicles was also decreased in a dose-dependent manner. In the C0.8 group, growing follicles were decreased compared with the other groups while the ratio was substantially increased in the C0.4 and C0.8 group. Co-treatment attenuated primordial follicle loss and reduced the upregulated ratio induced by cisplatin. Ovarian follicle dynamics in vivo was consistent with the in vitro results. Primordial follicles counts were statistically increased and the ratio was reduced in the rapamycin group compared with the control group. Primordial follicle counts were dramatically reduced in the cisplatin group whereas co-treatment with rapamycin slightly recovered its counts. There was no obvious difference in the number of growing follicles between the cisplatin group and other groups. The ratio was significantly increased in cisplatin-treated mice whereas decreased in the co-treatment group. The apoptosis rate of antral follicles in cisplatin-treated mice was higher than the other groups while the apoptosis rate was decreased in the co-treatment group in vivo. Compared with the control and rapamycin group, the mRNA expression of AMH, GDF9, and BMP15 were downregulated in the cisplatin group. The co-treatment group recovered the mRNA expression of BMP15. In addition, the expression of key protein of mTOR pathway rpS6 and its phosphorylated forms were increased in the cisplatin-treated group while co-treatment decreased their expression. Rapamycin attenuated the loss of primordial follicles induced by cisplatin through the inhibitory effect of rapamycin on the mTOR pathway. These results suggest that rapamycin may be an effective drug for the protection of ovarian function during chemotherapy.
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MOLECULAR REPRODUCTION AND DEVELOPMENT
MOL REPROD DEV
最新影响因子:2.812 | 期刊ISSN:1040-452X | CiteScore:2.41 |
出版周期:Monthly | 是否OA:YES | 出版年份:1988 |
期刊官方网址:http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1098-2795
自引率:3.10% | 研究方向:生物-发育生物学 |
出版地区:UNITED STATES |
SCI期刊coverage:Science Citation Index Expanded(科学引文索引扩展)
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MOLECULAR REPRODUCTION AND DEVELOPMENT 期刊简介
英文简介:
Molecular Reproduction and Development is an international journal that encompasses the molecular biology of reproductive and related developmental processes in humans multi-cellular animals and plants. In addition to studies in gamete biology (sex cells fertilization and early development) the journal publishes original research articles and invited reviews that impinge on modern reproductive biology such as genetics (including gene regulation and expression) transgenics cell biology and biochemistry as well as studies in physiology endocrinology anatomy and ultrastructure that provide a basis for molecular biological investigations. This unified approach achieves a balanced comprehensive coverage of modern reproductive and developmental biology. Topical coverage includes but is not limited to: spermatogenesis oogenesis fertilization; embryo and fetal development; micromanipulation of eggs and embryos; gene transfer and its applications (including studies with transgenics and the control of gene expression); the use of probes in the diagnosis of congenital defects sex determination and the study of developmental processes; new reproductive technologies in clinical and veterinary medicine; the molecular endocrinology of reproduction and reproductive behavior; molecular biological aspects of fertility; and genetic engineering of livestock and crops.
中文简介:(来自Google、百度翻译)
《分子繁殖与发展》是一本国际期刊,涵盖了人类多细胞动植物生殖和相关发育过程的分子生物学。除了对配子生物学(性细胞受精和早期发育)的研究外,该杂志还发表了原始的研究文章,并邀请了对现代生殖生物学如遗传学(包括基因调控和表达)、转基因细胞生物学和生物化学以及生理内分泌学研究产生影响的评论。为分子生物学研究提供基础的解剖和超微结构。这种统一的方法实现了现代生殖和发育生物学的平衡全面覆盖。局部报道包括但不限于:精子发生、卵发生、受精;胚胎和胎儿发育;卵和胚胎的微操作;基因转移及其应用(包括转基因研究和基因表达的控制);探针在先天性缺陷诊断中的应用;性别确定和发育过程研究;临床和兽医学的新生殖技术;生殖和生殖行为的分子内分泌学;生育的分子生物学方面;家畜和作物的基因工程。
MOLECULAR REPRODUCTION AND DEVELOPMENT 期刊中科院评价数据
最新中科院分区
大类(学科) | 小类(学科) | 学科排名 |
医学 |
BIOCHEMISTRY & MOLECULAR BIOLOGY(生物化学和分子生物学) 3区 CELL BIOLOGY(细胞生物学) 4区 DEVELOPMENTAL BIOLOGY(发育生物学) 3区 REPRODUCTIVE BIOLOGY(生殖生物学) 2区 |
128/293 105/190 11/42 6/29 |
最新公布的期刊年发文量
年度总发文量 | 年度论文发表量 | 年度综述发表量 |
109 | 70 | 39 |
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MOLECULAR REPRODUCTION AND DEVELOPMENT 期刊CiteScore评价数据
最新CiteScore值
引文计数(2018)
文献(2015-2017)
799次引用
332篇文献
CiteScore排名
序号 | 类别 | 排名 | 百分位 |
1 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Genetics
|
#144/310
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|
|
2 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Developmental Biology
|
#38/76
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|
|
3 |
大类(学科):Biochemistry, Genetics and Molecular Biology
小类(学科):Cell Biology
|
#150/264
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|
|
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