Pregnancy-associated urinary incontinence (PSUI) is a prevalent condition among pregnant women with gestational diabetes mellitus (GDM). PSUI significantly impacts quality of life, leading to both physical discomfort and emotional distress. Previous studies have shown that adequate intake of essential minerals and vitamins, such as iron (Fe), magnesium (Mg), zinc (Zn), and vitamins A and D, is crucial for maintaining metabolic homeostasis and minimizing oxidative stress. However, in women with GDM and PSUI, altered gene expression patterns, particularly of RXRA and TFRC, have been identified despite higher nutrient intake [1,2,3]. 
This paradox suggests that metabolic dysregulation during pregnancy may involve pathways not solely dependent on micronutrient availability. Understanding these associations could inform tailored nutritional strategies and therapeutic interventions, ultimately improving maternal and fetal outcomes. This study aims to evaluate the relationship between mineral and vitamin intake, gene expression levels of RXRA and TFRC, and the prevalence of PSUI in pregnant women with GDM. We hypothesize that despite higher intake of specific nutrients, altered gene expression is associated with metabolic and inflammatory pathways in GDM patients.

A cohort of 1,105 pregnant women with GDM was recruited from the DIAMATER study, conducted at Botucatu Medical School, UNESP, Brazil. Dietary intake data were collected using validated food frequency questionnaires, focusing on minerals and vitamins known to influence oxidative stress and gene regulation. Serum levels of Fe, Mg, Zn, vitamin A, and vitamin D were measured using standardized biochemical assays. Gene expression of RXRA and TFRC was quantified through real-time PCR, and protein expression was assessed via Western blotting. Additionally, markers of oxidative stress, including malondialdehyde (MDA) and protein carbonylation, were analyzed to determine the oxidative profile of the participants. Statistical analyses were performed using multivariate regression models to assess associations between dietary intake, serum levels, gene expression, and the presence of PSUI.

The analysis revealed that the GDM-PSUI group exhibited significantly lower expression of RXRA and TFRC genes compared to the non-PSUI GDM group (p < 0.05), despite higher dietary intake of Mg, Zn, and vitamin D. Notably, protein expression of TFRC was also diminished in the PSUI group. Correlation analysis indicated a negative relationship between serum mineral levels and TFRC expression, suggesting that mineral bioavailability might not directly enhance gene transcription or protein synthesis in this context. Oxidative stress markers, such as MDA and protein carbonylation, were elevated in PSUI cases, indicating a potential link between oxidative damage and reduced gene expression.

The findings challenge the assumption that higher intake of essential minerals and vitamins automatically translates into improved gene expression and reduced oxidative stress. It is possible that metabolic adaptations in GDM, influenced by hormonal and inflammatory responses, disrupt normal gene regulation mechanisms, leading to downregulation of TFRC and RXRA despite adequate nutritional intake. These results underscore the complexity of micronutrient metabolism in pregnancy and suggest that therapeutic approaches targeting oxidative stress and inflammatory pathways may be more effective than simple dietary supplementation.

Our study demonstrates that increased intake of essential minerals and vitamins does not necessarily improve gene expression related to oxidative stress regulation in GDM patients with PSUI. This underscores the importance of exploring alternative metabolic pathways and developing comprehensive therapeutic strategies to address this complex condition.

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Maserejian, N. N., Giovannucci, E. L., McVary, K. T., McGrother, C., and McKinlay, J.  B. (2010). Dietary Macronutrient and Energy Intake and Urinary Incontinence in  Women. American Journal of Epidemiology, 171(10), 1116–1125.  https://doi.org/10.1093/aje/kwq065