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    Fish Oil Supplementation Attenuates Offspring’s Neurodevelopmental Changes Induced by a Maternal High-Fat Diet in a Rat Model
    (MDPI AG, 2025-05-21)
    Yasna Muñoz
    ;
    Heidy Kaune
    ;
    Alexies Dagnino-Subiabre
    ;
    Gonzalo Cruz
    ;
    Jorge Toledo
    <jats:p>Background/Objectives: A maternal high-fat diet (HFD) impairs brain structure in offspring. In turn, fish oil (FO) rich in n-3 polyunsaturated fatty acids (PUFAs) has neuroprotective effects. Therefore, we investigated whether maternal HFD exposure affected the neurological reflexes, neuron morphology, and n-3 PUFA levels in the cerebral cortex of the offspring and whether these effects were mitigated by maternal FO consumption. Methods: Female Sprague Dawley rats received a control diet (CD, 10% Kcal fat) or HFD (45% Kcal fat) five weeks before mating and throughout pregnancy and lactation. From mating, a subgroup of HFD was supplemented with 11.4% FO into the diet (HFD-FO). Neurological reflexes were evaluated from postnatal day (PND) 3 until PND20. Brains were removed at PND22 for neuron morphology analysis. Moreover, fatty acid composition and transcripts of genes encoding for factors associated with synapse transmission (SNAP-25), plasticity (BDNF), transport of DHA (MFSD2a), and inflammation (NF-κB and IL-1β) were quantified in prefrontal, motor, and auditory cortices. Results: FO diminished the effects of HFD on the number of thin and mushroom-shaped dendritic spines in the cerebral cortex in both sexes. It also reversed the HFD effects on the motor and auditory reflexes in female and male offspring, respectively. In males, FO up-regulated Bdnf transcript levels in the motor cortex compared with CD and HFD. In females, n-3 PUFAs were higher in HFD and HFD-FO than in CD in the auditory cortex. Conclusions: Our results highlight the protective role of maternal dietary n-3 PUFAs in counteracting the effects induced by HFD on the acquisition of neurological reflexes and neuronal morphology in the cerebral cortex of the offspring of both sexes.</jats:p>
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    Women with polycystic ovary syndrome (PCOS): Likelihood of cooccurring neuropsychiatric conditions and the dual hit hypothesis
    (Elsevier BV, 2025-04)
    Juan Pablo Del Río
    ;
    Alexandros Tsompanidis
    ;
    Pablo A. Gaspar
    ;
    Alejandro Maturana-Hurtado
    ;
    Gonzalo M. Rojas-Costa
    Scopus© Citations 7  6
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    Oxidative Stress in Polycystic Ovary Syndrome: Impact of Combined Oral Contraceptives
    (2024)
    Nicolás Santander
    ;
    Esteban G. Figueroa
    ;
    Alejandro González-Candia
    ;
    Manuel Maliqueo
    ;
    Bárbara Echiburú
    <jats:p>Polycystic Ovary Syndrome (PCOS) is a complex hormonal disorder that is associated with heightened metabolic risks. While oxidative stress (OS) is known to play a role in PCOS, the precise nature of the relationship between PCOS and increased OS remains not entirely understood. Combined oral contraceptives (COCs) are the first-line treatment to regulate menstrual cycles and androgen levels, but their impact on oxidative stress requires further study. We conducted a transcriptomic analysis using RNAseq and assessed the levels of various oxidative stress (OS) markers in serum samples from women with PCOS and controls and whether they were using combined oral contraceptives (COCs), including enzymatic activities, FRAP, and 8-isoprostane (8-iso). A total of 359 genes were differentially expressed in women with PCOS compared to control women. Genes differentially expressed were enriched in functions related to inflammation and, interestingly, oxidative stress response. In controls, 8-iso levels were increased in women using COCs, whereas in women with PCOS, 8-iso levels were reduced in those using oral contraceptives (191.1 ± 97 vs. 26.4 ± 21 pg/mL, p: &lt;0.0001). Correlation analyses showed a trend for a negative correlation between 8-iso and Ferriman score in women with PCOS consuming COCs (r = −0.86, p = 0.06) and a negative correlation between GSH and hyperandrogenism in women with PCOS (r = −0.89, p = 0.01). These results reveal the presence of lipid peroxidation in women with PCOS, which was modified by the use of COCs, providing new insights into the pathophysiology of PCOS in the Chilean population.</jats:p>
    Scopus© Citations 4  1
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    Folate and Vitamin B12 Levels in Chilean Women with PCOS and Their Association with Metabolic Outcomes
    (2024)
    Matías Carrasco-Cabezas
    ;
    Taís Silveira Assmann
    ;
    ;
    Leslie Cerpa
    ;
    Susan Calfunao
    <jats:p>Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; p &lt; 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (&lt;300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.</jats:p>
    Scopus© Citations 1  3
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    Linoleic and Arachidonic Fatty Acids and their Potential Relationship
    with Inflammation, Pregnancy, and Fetal Development
    (2024)
    Macarena Ortiz
    ;
    Daniela Álvarez
    ;
    Yasna Muñoz
    ;
    Nicolás Crisosto
    ;
    Rodrigo Valenzuela
    <jats:sec> <jats:title>Abstract:</jats:title> <jats:p>A healthy maternal diet must consider an appropriate supply of long-chain polyunsaturated fatty acids (LCPUFAs) precursors to ensure adequate growth and development of the fetus. In this regard, n-6 PUFAs, predominantly linoleic (C18:2 n-6, LA) and arachidonic acid (C20:4 n-6), have a central role in the development of the central nervous system because they are part of the membrane structure and participate in the metabolism and signal transduction of cells. Nevertheless, they can also be transformed into inflammatory metabolites promoting the pathogenesis of cardiovascular diseases, cancer, and autoimmune or inflammatory conditions. In modern westernized societies, there is a high dietary consumption of foods rich in n-6 PUFAs which could have detrimental consequences for the fetus and neonate due to excessive exposure to these fatty acids (FAs).</jats:p> </jats:sec> <jats:sec> <jats:title>Objective:</jats:title> <jats:p>To summarize the evidence of maternal, placental, and fetal alterations that an excessive intake of n-6 polyunsaturated FAs (PUFAs), LA, and AA, could produce during pregnancy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>A thorough review of the literature regarding the effects of n-6 PUFAs during pregnancy and lactation including in vivo and in vitro models, was carried out using the PubMed database from the National Library of Medicine-National Institutes of Health.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>An elevated intake of n-6 PUFA, specifically LA, during pregnancy influences children's motor, cognitive, and verbal development during infancy and early childhood. Similarly, they could harm the placenta and the development of other fetal organs such as the fat tissue, liver, and cardiovascular system.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusion:</jats:title> <jats:p>Maternal diet, specifically LA intake, could have significant repercussions on fetal development and long-term consequences in the offspring, including the possibility of future metabolic and mental diseases. It would be necessary to focus on the prevention of these alterations through timely dietary interventions in the target population.</jats:p> </jats:sec>
    Scopus© Citations 6  11
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    Scopus© Citations 11  3
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    Effects of a High-Fat Diet and Docosahexaenoic Acid during Pregnancy on Fatty Acid Composition in the Fetal Livers of Mice
    (2023)
    Daniela Álvarez
    ;
    Macarena Ortiz
    ;
    Gabriel Valdebenito
    ;
    Nicolás Crisosto
    ;
    Bárbara Echiburú
    <jats:p>A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4–6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.</jats:p>
    Scopus© Citations 2
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    Association between maternal obesity, essential fatty acids and biomarkers of fetal liver function
    (2023)
    Macarena Ortiz
    ;
    Francisca Sánchez
    ;
    Daniela Álvarez
    ;
    Cristian Flores
    ;
    Francisca Salas-Pérez
      7Scopus© Citations 5