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Published on: May 2, 2017
miR-155 and miR-122 Expression of Spermatozoa in Obese Subjects
Paulina López1, Andrea Castro2, Martha Flórez2
1Micronutrient Laboratory, Institute of Nutrition and Food Technology, University of Chile, Santiago, Chile.
Abstract:
Obesity is characterized by mild chronic inflammation that is linked with impaired iron homeostasis. Studies in human and murine show that there is a transgenerational epigenetic inheritance via the gametes in obesity; however, there is little information on changes in the expression of microRNAs related to inflammation and iron homeostasis in spermatozoa from obese subjects. The present study investigated the expression of microRNAs related to inflammation (miR-21 y miR-155) and iron nutrition (miR-122 and miR-200b) in plasma, peripheral blood mononuclear cells (PBMC) and spermatozoa from normozoospermic controls (Cn; n = 17; BMI: 24.6 ± 2.0) and obese (Ob; n = 17; BMI: 32.6 ± 4.4) men. To determine the inflammation levels, we measured IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP1) by Magnetic Luminex® Assay. mRNA expression of IL6, TNF-α, and hepcidin (HAMP) in PBMC were evaluated by RT-qPCR. The analysis of microRNAs was performed using the Taqman® assays. The iron content in PBMC, seminal plasma, and spermatozoa was determined by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). High serum IL6, TNF-α, and MCP1 levels were observed in Ob group (p < 0.05). Gene expression analysis showed an increased abundance relative of TNF-α (p = 0.018), HAMP (p = 0.03), and IL6 (p = 0.02) in PBMC from obese subjects. Also, we observed high levels of serum ferritin (p = 0.03), iron content in seminal plasma (p = 0.04), and spermatozoa (p = 0.002), but lower serum Fe (p = 0.007) in obese subjects. In the Ob group, a high expression of miR-155 (p = 0.02) and miR-21 (p = 0.03) was observed in PBMC and miR-122 (p = 0.03) in plasma. In sperm, both miR-155 (p = 0.004) and miR-122 (p = 0.028) were high in the Ob group. Our results showed that obese subjects have increased expressions of miR-155 and miR-122, two microRNAs that were previously related with inflammation and iron metabolism, respectively, at both the systemic and sperm levels.
Insights
Obese men show increased inflammation and altered iron levels, with higher expression of microRNAs miR-155 and miR-122 in both blood and sperm. These findings link obesity to systemic and sperm-level changes in inflammation and iron metabolism.
Area of Science:
- Reproductive Biology
- Endocrinology
- Epigenetics
Background:
- Obesity is associated with chronic inflammation and impaired iron homeostasis.
- Transgenerational epigenetic inheritance via gametes in obesity is known, but microRNA changes in obese spermatozoa are understudied.
- MicroRNAs play crucial roles in regulating inflammation and iron metabolism.
Purpose of the Study:
- To investigate the expression of inflammation-related microRNAs (miR-21, miR-155) and iron-related microRNAs (miR-122, miR-200b) in plasma, PBMCs, and spermatozoa of obese men.
- To assess inflammation markers (IL-6, TNF-α, MCP1) and iron levels in obese and control subjects.
Main Methods:
- Analysis of microRNA expression in plasma, peripheral blood mononuclear cells (PBMCs), and spermatozoa using Taqman® assays.
- Measurement of inflammatory markers (IL-6, TNF-α, MCP1) via Magnetic Luminex® Assay.
- Quantification of mRNA expression (IL6, TNF-α, HAMP) in PBMCs by RT-qPCR.
- Determination of iron content in PBMCs, seminal plasma, and spermatozoa using Inductively Coupled Plasma Mass Spectrometry (ICP-MS).
Main Results:
- Obese subjects exhibited higher serum IL-6, TNF-α, and MCP1 levels, and increased TNF-α, HAMP, and IL6 mRNA expression in PBMCs.
- Elevated serum ferritin and seminal plasma/spermatozoa iron content were observed in obese men, alongside lower serum iron.
- Increased expression of miR-155 and miR-21 in PBMCs, miR-122 in plasma, and notably, high levels of miR-155 and miR-122 in spermatozoa from obese men.
Conclusions:
- Obesity leads to significant alterations in systemic inflammation and iron homeostasis, reflected in both blood and seminal plasma.
- Obese men show increased expression of miR-155 and miR-122 at both systemic (PBMC, plasma) and sperm levels.
- These microRNA changes in spermatozoa may represent an epigenetic link between obesity, inflammation, and altered iron metabolism, potentially impacting offspring health.
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