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Sarcoma-180 tumor affects the quality of oocytes in mice.

ABSTRACT: Numerous factors can affect the quality of oocytes; however, the effects of cancer on the quality of oocytes and the underlying mechanisms remain unclear. In the present study, the effects of the sarcoma-180 (S-180) cell line on the quality of oocytes were investigated using S-180 tumor-bearing mice. In total, 42 female C57BL/6J mice were randomly divided into the tumor-bearing group and the control group, with 21 mice per group. The weight of the mice and ovaries were recorded, and blood glucose, serum insulin, lipopolysaccharide, triglyceride (TG) and total cholesterol (TC) levels were analyzed using the corresponding detection kits. Hematoxylin and eosin staining was performed to observe the pathological changes of the ovarian tissue, and reverse transcription-quantitative PCR (RT-qPCR) was used to analyze the expression levels of meiosis arrest female 1 (MARF1), SUMO-specific protease 7 (SENP7), aralkylamine N-acetyltransferase (AANAT), cell division cycle 25B and glycine-rich protein 3. The results of the present study revealed that the number of oocytes in the two groups of mice was similar; however, the number of abnormal oocytes was increased in the tumor-bearing group. The serum levels of TG and TC were significantly elevated in the tumor-bearing group compared with in the control group (P<0.01). Additionally, RT-qPCR analysis demonstrated that the expression levels of SENP7 were downregulated, while the expression levels of MARF1 and AANAT were upregulated in the ovaries of the tumor-bearing group compared with in the control group (P<0.01). In conclusion, the findings of the present study suggested that cancer may affect the reproductive system of mice and decrease the quality of oocytes by regulating the expression levels of reproduction-associated genes. These results provided novel insights into the reproductive ability of patients with cancer.

SUBMITTER: Chen Z

PROVIDER: S-EPMC7816293 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Sarcoma-180 tumor affects the quality of oocytes in mice.

Chen Zihang Z Wang Simin S Luo Xuexia X Yang Yanhong Y

Oncology letters 20210106 3

Numerous factors can affect the quality of oocytes; however, the effects of cancer on the quality of oocytes and the underlying mechanisms remain unclear. In the present study, the effects of the sarcoma-180 (S-180) cell line on the quality of oocytes were investigated using S-180 tumor-bearing mice. In total, 42 female C57BL/6J mice were randomly divided into the tumor-bearing group and the control group, with 21 mice per group. The weight of the mice and ovaries were recorded, and blood glucos ...[more]

PMID: 33574920

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Project description:In solid tumors, HIF1 upregulates the expression of hundreds of genes involved in cell survival, tumor growth, and adaptation to the hypoxic microenvironment. HIF1 stabilization and activity are suppressed by prolyl and asparagine hydroxylases, which require oxygen as a substrate and ascorbate as a cofactor. This has led us to hypothesize that intracellular ascorbate availability could modify the hypoxic HIF1 response and influence tumor growth. In this study, we investigated the effect of variable intracellular ascorbate levels on HIF1 induction in cancer cells in vitro, and on tumor-take rate and growth in the Gulo-/- mouse. These mice depend on dietary ascorbate, and were supplemented with 3,300 mg/L, 330 mg/L, or 33 mg/L ascorbate in their drinking water, resulting in saturating, medium, or low plasma and tissue ascorbate levels, respectively. In Lewis lung carcinoma cells (LL/2) in culture, optimal ascorbate supplementation reduced HIF1 accumulation under physiological but not pathological hypoxia. LL/2, B16-F10 melanoma, or CMT-93 colorectal cancer cells were implanted subcutaneously into Gulo-/- mice at a range of cell inocula. Establishment of B16-F10 tumors in mice supplemented with 3,300 mg/L ascorbate required an increased number of cancer cells to initiate tumor growth compared with the number of cells required in mice on suboptimal ascorbate intake. Elevated ascorbate intake was also associated with decreased tumor ascorbate levels and a reduction in HIF1? expression and transcriptional activity. Following initial growth, all CMT-93 tumors regressed spontaneously, but mice supplemented with 33 mg/L ascorbate had lower plasma ascorbate levels and grew larger tumors than optimally supplemented mice. The data from this study indicate that improved ascorbate intake is consistent with increased intracellular ascorbate levels, reduced HIF1 activity and reduced tumor initiation and growth, and this may be advantageous in the management of cancer.

Project description:BackgroundStudies suggested that PM2.5 exposure could lead to adverse reproductive effects on male animals. However, the underlying mechanism is still not clear. Besides, animals in the majority of previous studies were exposed to PM2.5 through intratracheal instillation which should be improved. In addition, limited amount of research has been conducted in China where the PM2.5 concentration is higher and the PM2.5 components are different. The aim of this work is to explore the effects of concentrated ambient PM2.5 (CAP) on mice sperm quality and testosterone biosynthesis.MethodsA total of 12 male C57BL/6 mice were exposed to filtered air (FA) or CAP for 125 days using the Shanghai Meteorological and Environmental Animal Exposure System. The mice sperm concentration, sperm motility, DNA fragmentation index, high DNA stainability and plasma testosterone were analyzed. Testicular histology and sperm morphology were observed through optical microscope. Testosterone biosynthesis related gene expressions were analyzed using real-time PCR, including cytochrome P450 CHOL side-chain cleavage enzyme (P450scc), steroidogenic acute regulatory protein (StAR), 3?-hydroxysteroid dehydrogenase (3? HSD), 17?-hydroxysteroid dehydrogenase, cytochrome P450 aromatase (P450arom), estrogen receptor (ER), androgen receptor (AR) and follicle stimulating hormone receptor (FSHR).ResultsExposure to CAP resulted in disturbance of various stages of spermatogenesis and significant higher percentage of abnormal sperm (FA vs. CAP: 24.37% vs. 44.83%) in mice testis. CAP exposure significantly decreased sperm concentration (43.00 × 106 vs. 25.33 × 106) and motility (PR: 63.58% vs. 55.15%; PR + NP: 84.00% vs. 77.08%) in epididymis. Plasma testosterone concentration were significantly declined (0.28 ng/ml vs. 0.69 ng/ml) under CAP exposure. Notably, the levels of testosterone biosynthesis related genes, StAR, P450scc, P450arom, ER and FSHR were significantly decreased with CAP exposure.ConclusionConcentrated ambient PM2.5 exposure altered mice sperm concentration, motility and morphology, which might be mediated primarily by the decline in testosterone concentration and testosterone biosynthesis process.

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Sarcoma-180 tumor affects the quality of oocytes in mice.

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Sarcoma-180 tumor affects the quality of oocytes in mice.

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