Sex modifies the renal consequences of high fructose consumption introduced after weaning.

After lactation, many children consume fructose-rich processed foods. However, overconsumption of these foods can predispose individuals to non-communicable chronic diseases, which can have different repercussions depending on the sex. Thus, we evaluated the effects of fructose overload introduced after weaning on the renal function of young rats of both sexes. Methods: After weaning, male and female offspring of Wistar rats were assigned to drink water (the male/water and female/water groups) or 20% D-fructose solution (male/fructose and female/fructose groups). Food and water or fructose solution was offered ad libitum. Rats were evaluated at 4 months. Parameters analyzed: blood pressure, body weight, triglyceride levels, glomerular filtration rate, sodium, potassium, calcium, and magnesium excretion, macrophage infiltration, and eNOS and 8OHdG expression in renal tissue. CEUA-UNIFESP: 2757270117. Results: Fructose intake affected the blood pressure, body weight, and plasma triglyceride in all rats. Glomerular filtration rate was significantly reduced in males that received fructose when compared to that of the control group. Sodium and potassium excretion decreased in all fructose-treated rats; however, the excreted load of these ions was significantly higher in females than in males. In the female control group, calcium excretion was higher than that of the male control group. Fructose overload increased magnesium excretion in females, and also increased macrophage infiltration and reduced eNOS expression in both males and females. Conclusion: Fructose overload introduced after weaning caused metabolic and renal changes in rats. Renal function was more affected in males; however, several significant alterations were also observed in the female-fructose group.

Effects of maternal fructose intake on the offspring's kidneys.

Fructose overload is associated with cardiovascular and metabolic disorders. During pregnancy, these alterations may affect the maternal environment and predispose offspring to diseases. AIMS: To evaluate the renal morphology and function of offspring of dams that received fructose overload during pregnancy and lactation. METHODS: Female Wistar rats were divided into the control (C) and fructose (F) groups. C received food and water ad libitum, and F received food and d-fructose solution (20%) ad libitum. The d-fructose offer started 1 week before mating and continued during pregnancy and lactation. The progeny were designated as control (C) or fructose (F); after weaning, half of the F received water to drink (FW), and half received d-fructose (FF). Blood pressure (BP) and renal function were evaluated. The expression of sodium transporters (NHE3-exchanger, NKCC2 and NCC-cotransporters, and ENaC channels) and markers of renal dysfunction, including ED1 (macrophage), eNOS, 8OHdG (oxidative stress), renin, and ACE 1 and 2, were evaluated. CEUA-UNIFESP: 2757270117. The FF group presented with reduced glomerular filtration rate and urinary osmolarity, increased BP, proteinuria, glomerular hypertrophy, macrophage infiltration, and increased expression of transporters (NHE3, NCC, and ENaC), 8OHdG, renin, and ACE1. The FW group did not show increased BP and renal functional alterations; however, it presented glomerular hypertrophy, macrophage infiltration, and increased expression of the transporters (NHE3, NKCC2, NCC, and ENaC), renin, and ACE1. These data suggest that fructose overload during fetal development alters renal development, resulting in the increased expression of renin, ACE1, and sodium transporters, thus predisposing to hypertension and renal dysfunction.

Maternal fructose intake during pregnancy and lactation: Later effects on renal function.

Excessive fructose consumption has been associated with hypertension and metabolic disorders and can alter physiological adaptations during pregnancy, with long-term detrimental consequences. This study evaluated in post-weaning mothers the effects of increased fructose consumption during pregnancy and lactation on blood pressure and renal function. Female Wistar rats were assigned to one of four experimental groups: non-pregnant control (NPC); pregnant control (PC); non-pregnant fructose (NPF), and pregnant fructose (PF). Control rats had free access to food and water, while the fructose groups had free access to food and to a 20% fructose solution, over the time period of the experiment. The systolic BP and renal function parameters were measured at the end of the experimental period, one week after weaning (28 days after delivery). The results were presented as means ± standard error. Higher values of BP were observed in both pregnant and non-pregnant rats treated with fructose compared to control. Creatinine clearance was reduced only in the PF group; however, both the PF and NPF groups had reduced Na+ and K+ excretions. In the PF group, there was also glomerular enlargement and changes in the media/lumen (M/L) ratio of interlobular arteries. Additionally, the PF group showed increased macrophage infiltration and expression of alpha-SM-actin and reduced expression of nitric-oxide-synthase endothelial in renal tissue. These findings suggest that the association of high fructose intake with pregnancy aggravated kidney changes that persisted for up to four weeks after delivery, which may represent a risk factor for maternal health.

Cross-sex testosterone therapy modifies the renal morphology and function in female rats and might underlie increased systolic pressure.

Testosterone esters are hormones commonly used for affirming gender identity in transmen. The present study evaluates the effect of testosterone on renal morphology and function in an animal model submitted to cross-sex hormone therapy used for transmen. Two-month-old Wistar rats were divided into three groups: male control (MC), female control (FC), and female on testosterone therapy (FTT). The FTT group received testosterone cypionate (3.0 mg/kg, i.m.), and the MC and MF groups received vehicle oil every 10 days for 4 months. Renal function and indirect systolic blood pressure (SBP) measurements were evaluated at 6 months of age. Plasma and urine concentrations of urea, creatinine, sodium, potassium, osmolality, and glomerular filtration rate (GFR) were measured. The kidneys were weighed, paraffin-embedded, and histological sections were prepared to evaluate the glomerular area. We verified that the FTT group, in comparison to FC, had increased kidney weight [MC, 3.2 ± 0.05; FC, 1.8 ± 0.04; FTT, 2.2 ± 0.06; g], decreased urine osmolarity [MC, 486.9 ± 18.3; FC, 1012.0 ± 5.4; FTT, 768.2 ± 40.3 mOsm/L/g kw], reduced GFR [MC, 0.77 ± 0.04; FC, 0.78 ± 0.02; FTT, 0.67 ± 0.03; mL/min/g kw], larger glomerular area [MC, 9334 ± 120.8; FC, 7884 ± 112.8; FTT, 9078 ± 133.4 µm2 ], and higher SBP [MC, 126 ± 3.4; FC, 119 ± 1.0; FTT, 131 ± 1.4; mmHg]. Sodium excretion was higher in FC and FTT in comparison to MC [MC, 0.34 ± 0.05; FC, 0.56 ± 0.06; FTT, 0.54 ± 0.04; mEq/24 h/g kw]. Cross-sex hormone therapy with testosterone in female rats induces renal morphofunctional changes and may underlie increased systolic pressure, suggesting an adaptation similar to what is observed in transmen on long-term testosterone therapy.

Programmed Adult Kidney Disease: Importance of Fetal Environment.

The Barker hypothesis strongly supported the influence of fetal environment on the development of chronic diseases in later life. Multiple experimental and human studies have identified that the deleterious effect of fetal programming commonly leads to alterations in renal development. The interplay between environmental insults and fetal genome can induce epigenetic changes and lead to alterations in the expression of renal phenotype. In this review, we have explored the renal development and its functions, while focusing on the epigenetic findings and functional aspects of the renin-angiotensin system and its components.

Effects of sleep restriction during pregnancy on lipids and glucose homeostasis of female offspring submitted to ovariectomy.

Sleep shortening during pregnancy may alter the mother's environment, affecting the offspring. Thus, the present study evaluated the metabolic profile of female offspring from sleep-restricted rats during the last week of pregnancy. Pregnant Wistar rats were distributed into two groups: control (C) and sleep restriction (SR). The SR was performed 20 h/day, from 14th to 20th day of pregnancy. At 2 months, half of the offspring were subjected to ovariectomy (OVX); the others, to sham surgery. Studied groups were Csham, Covx, SRsham and SRovx. Cholesterol (HDL, LDL and C-total), triglycerides (TG) and glucose and insulin tolerance tests (GTT-ITT) were evaluated at 8 months. RSsham presented higher values of TG, while SRovx presented higher TG, LDL and C-total. Basal glucose concentration was increased in SRsham and SRovx. These data suggest that SR during pregnancy may be a risk factor for the development of diseases in adult female offspring.

Sleep restriction during pregnancy and its effects on blood pressure and renal function among female offspring.

The influence of sleep restriction (SR) during pregnancy on blood pressure and renal function among female adult offspring was investigated. Pregnant Wistar rats were distributed into control and SR groups. The SR was performed between the 14th and 20th days of pregnancy (multiple platforms method for 20 h/day). At 2 months of age, half of the offspring from both groups were subjected to an ovariectomy (ovx), and the other half underwent sham surgery. The groups were as follows: control sham (Csham), control ovx (Covx), SR sham (SRsham), and SR ovx (SRovx). Renal function markers and systolic blood pressure (BPi, indirect method) were evaluated at 4, 6, and 8 months. Subsequently, the rats were euthanized, kidneys were removed, and processed for morphological analyses of glomerular area (GA), number of glomeruli per mm3 (NG), and kidney mass (KM). Increased BPi was observed in the Covx, SRsham, and SRovx groups compared to Csham at all ages. Increased plasma creatinine concentration and decreased creatinine clearance were observed in the SRsham and SRovx groups compared to the Csham and Covx groups. The SRovx group showed higher BPi and reduced creatinine clearance compared to all other groups. The SRovx group showed reduced values of GA and KM, as well as increased NG, macrophage infiltration, collagen deposit, and ACE1 expression at the renal cortex. Therefore, SR during pregnancy might be an additional risk factor for developing renal dysfunction and increasing BP in female adult offspring. The absence of female hormones exacerbates the changes caused by SR.