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. 2024 Jan 19;19(1):1.
doi: 10.1186/s12263-024-00737-6.

Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice

Yanru Zhang  1 , Ruike Ding  1 , Yulin Zhang  1 , Jia Qi  1 , Wenbin Cao  1 , Lijun Deng  2 , Lin Zhou  1 , Yun Ye  3 , Ying Xue  4 , Enqi Liu  5   6
Affiliations

Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice

Yanru Zhang et al. Genes Nutr. .

Abstract

Background: Obese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity.

Results: Our results showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization, and glutamine transport, which are closely related to spermatogenesis, sperm development, and sperm viability in mice.

Conclusions: In obese mice, we observed downregulation of DMT1 in the duodenum and upregulation of miR-135b in the spermatozoa.

Keywords: DMT1; Epigenetic; Iron deficiency; MicroRNAs; Obesity.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Effects of HFD on testicular morphology and serum iron levels. A Morphological analysis of testis from SD and HFD groups. B Serum iron levels were significantly decreased in HFD-fed obese mice compared to SD-fed control mice. Data are expressed as mean ± SEM; **p < 0.01
Fig. 2
Fig. 2
HFD-induced obesity reduces the protein and mRNA expression of duodenal DMT1. A Immunohistochemical staining of duodenal DMT1 in SD and HFD mice. The mRNA expression levels of B DMT1 and C FPN in SD and HFD mice. Data are expressed as SEM ± mean; *p < 0.05; ns indicates p > 0.05
Fig. 3
Fig. 3
Expression of miR-135b in sperm and functional annotation of DEGs. A Expression of miR-135b from sperm of SD vs HFD mice; *p < 0.05. B Bubble diagram of GO for 90 DEGs. Venn diagrams of 90 DEGs and genes related to C male sterility phenotype, D fertilization, E spermatogenesis, and F spermatozoa development
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