Maternal obesity induces sex-specific changes in the endocannabinoid system of the hypothalamus and dorsal hippocampus of offspring associated with anxiety-like behavior in adolescent female rats.

Maternal obesity during perinatal period increases the risk of metabolic and behavioral deleterious outcomes in the offspring, since it is critical for brain development, maturation, and reorganization. These processes are highly modulated by the endocannabinoid system (ECS), which comprises the main lipid ligands anandamide and 2-arachidonoylglycerol, cannabinoid receptors 1 and 2 (CB1R and CB2R), and several metabolizing enzymes. The ECS is overactivated in obesity and it contributes to the physiological activity of the hypothalamus-pituitary-adrenal (HPA) axis, promoting stress relief. We have previously demonstrated that maternal high-fat diet during gestation and lactation programmed the food preference for fat in adolescent male offspring and adult male and female offspring. In the present study, we hypothesized that maternal diet-induced obesity would induce sex-specific changes of the ECS in the hypothalamus and dorsal hippocampus of rat offspring associated with dysregulation of the HPA axis and stress-related behavior in adolescence. Rat dams were fed a control (C) or an obesogenic high-fat high-sugar diet (OD) for nine weeks prior to mating and throughout gestation and lactation. Maternal obesity differentially altered the CB1R in the hypothalamus of neonate offspring, with significant increase in male but not in female pups, associated with decreased CB2R prior to obesity development. In adolescence, maternal obesity induced anxiety-like behavior only in adolescent females which was associated with increased content of CB1R in the dorsal hippocampus. Our findings suggest that the early origins of anxiety disorders induced by maternal exposome is associated with dysregulation of the brain ECS, with females being more susceptible.

Impact of neonatal hyperoxia on adult cardiac autonomic function in rats: Role of angiotensin II type 1 receptor activation.

Individuals born preterm present altered cardiac autonomic function, a risk factor to heart diseases. Neonatal renin-angiotensin-system activation contributes to adult cardiomyopathy in rats exposed to neonatal hyperoxia, a well-established model of preterm birth-related conditions. Central angiotensin II receptor activation is a key modulator of the autonomic drive to the heart. Whether neonatal hyperoxia leads to alteration of the cardiac autonomic function through activation of the angiotensin II receptor type 1 (AT1) is unknown and was examined in the present study. Sprague-Dawley pups were exposed to hyperoxia or room air from postnatal days 3-10. AT1 antagonist losartan or water was given orally postnatal days 8-10. Blood pressure, autonomic function, left ventricular sympathetic innervation, ß-adrenergic-receptors expression, and AT1 expression in the solitary-tract-nucleus were examined in adult rats. Neonatal hyperoxia led to loss of day-night blood pressure variation, decreased heart rate variability, increased sympathovagal balance, increased AT1 expression in the solitary-tract, decreased left ventricle sympathetic innervation, and increased ß1-adrenergic-receptor protein expression. Losartan prevented the autonomic changes and AT1 expression in the solitary-tract but did not impact the loss of circadian blood pressure variation nor the changes in sympathetic innervation and in ß1-adrenergic-receptor expression. In conclusion, neonatal hyperoxia leads to both central autonomic and cardiac sympathetic changes, partly programmed by neonatal activation of the renin-angiotensin system.

Is Our Limited Understanding of the Effects of Nerve Stimulation Resulting in Poor Outcomes and the Need for Better "Rescue Programming" in SNM and PTNS, and Lost Opportunities for New Sites of Stimulation? ICI-RS 2024.

AIMS: Sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) are strongly recommended by international guidelines bodies for complex lower urinary tract dysfunctions. However, treatment failure and the need for rescue programming still represent a significant need for long-term follow-up. This review aimed to describe current strategies and future directions in patients undergoing such therapies. MATERIALS AND METHODS: This is a consensus report of a Think Tank discussed at the Annual Meeting of the International Consultation on Incontinence - Research Society (ICI-RS), June 6-8, 2024 (Bristol, UK): "Is our limited understanding of the effects of nerve stimulation resulting in poor outcomes and the need for better 'rescue programming' in SNM and PTNS, and lost opportunities for new sites of stimulation?" RESULTS: Rescue programming is important from two different perspectives: to improve patient outcomes and to enhance device longevity (for implantable devices). Standard SNM parameters have remained unchanged since its inception for the treatment of OAB, nonobstructive urinary retention, and voiding dysfunction. SNM rescue programming includes intermittent stimulation (cycling on), increased frequency and changes in pulse width (PW). The effect of PW setting on SNM outcomes remains unclear. Monopolar configurations stimulate more motor nerve fibers at lower stimulation voltage; hence, this could be an option in patients who failed bipolar stimulation in the long term. Unfortunately, there is little evidence for rescue programming for PTNS. However, the development of implantable devices for intermittent stimulation of the tibial nerve may increase long-term adherence to therapy and increase interest in alternative programming. There has been recent promising neurostimulation targeting the pudendal nerve (PNS), especially in BPS/IC. More recently, preliminary data addressed the benefits of high-frequency bilateral pudendal nerve block for DESD and adaptive PNS on both urgency and stress UI in women. CONCLUSION: The exploration of rescue programming and new stimulation sites remains underutilized, and there are opportunities that could potentially expand the therapeutic applications of nerve stimulation. By broadening the range of target sites, clinicians may be able to tailor treatments according to individual patient needs and underlying conditions, thereby improving overall outcomes. However, further studies are still needed to increase the level of evidence, potentially allowing for an individualized treatment both in patients who are candidates for electrostimulation and in those who have already received surgical implants but seek a better outcome.

Neonatal undernutrition induced by litter size expansion alters testicular parameters in adult Wistar rats.

Several models of maternal undernutrition reveal impairment of testicular development and compromise spermatogenesis in male offspring. The expansion of the litter size model, valuable for studying the impact of undernutrition on early development, has not yet been used to evaluate the consequences of early undernutrition in the adult male reproductive system. For this purpose, pups were raised in either normal litter (ten pups/dam) or large litter (LL; sixteen pups/dam). On postnatal day 90, sexual behaviour was evaluated or blood, adipose and reproductive tissues were collected for biochemical, histological and morphological analysis. Adult LL animals were lighter and thinner than controls. They showed increased food intake, but decrease of retroperitoneal white adipose tissue weight, glycaemia after oral glucose overload and plasma concentration of cholesterol. Reproductive organ weights were not altered by undernutrition, but histopathological analysis revealed an increased number of abnormal seminiferous tubules and number of immature spermatids in the tubular lumen of LL animals. These animals also showed reduction in total spermatic reserve and daily sperm production in the testes. Undernutrition decreased the number of Sertoli cells, and testosterone production was increased in the LL group. Mitochondrial activity of spermatozoa remained unchanged between experimental groups, suggesting no significant impact on the energy-related processes associated with sperm function. All animals from both experimental groups were considered sexually competent, with no significant difference in the parameters of sexual behaviour. We conclude that neonatal undernutrition induces histological and physiological testicular changes, without altering sperm quality and sexual behaviour of animals.

Influence of Infill Patterns on the Shape Memory Effect of Cold-Programmed Additively Manufactured PLA.

In four-dimensional additive manufacturing (4DAM), specific external stimuli are applied in conjunction with additive manufacturing technologies. This combination allows the development of tailored stimuli-responsive properties in various materials, structures, or components. For shape-changing functionalities, the programming step plays a crucial role in recovery after exposure to a stimulus. Furthermore, precise tuning of the 4DAM process parameters is essential to achieve shape-change specifications. Within this context, this study investigated how the structural arrangement of infill patterns (criss-cross and concentric) affects the shape memory effect (SME) of compression cold-programmed PLA under a thermal stimulus. The stress-strain curves reveal a higher yield stress for the criss-cross infill pattern. Interestingly, the shape recovery ratio shows a similar trend across both patterns at different displacements with shallower slopes compared to a higher shape fixity ratio. This suggests that the infill pattern primarily affects the mechanical strength (yield stress) and not the recovery. Finally, the recovery force increases proportionally with displacement. These findings suggest a consistent SME under the explored interval (15-45% compression) despite the infill pattern; however, the variations in the mechanical properties shown by the stress-strain curves appear more pronounced, particularly the yield stress.

Mixed-integer disciplined convex programming approach applied to the optimal energy supply of near-zero energy buildings.

Energy needs in the buildings sector accounts for 40 % of global energy demand. Therefore, the implementation of several renewable energy sources is necessary to reduce this demand. The design stage of a decentralized generation project requires quantifying the power to be installed and the energy forecast for each source throughout the useful life of the building. This study develops a novel optimization algorithm for a long-term economic function based on mixed-integer disciplined convex programming (MIDCP) which guarantees the sustainability of the building and its energy systems. The robust algorithm integrates risk management of intermittent sources, technical and economic parameters of selected technologies, and life cycle analysis (LCA) of different energy systems, including storage. Furthermore, the penetration of green hydrogen into the distributed generation mix is evaluated as an important contribution. Meteorological and energy demand variables of two antagonistic scenarios were also used as inputs to the algorithm. As a result, the optimal energy supply sizing for tertiary buildings in the two defined locations was obtained. The results of the simulations have achieved an optimal convergence of 100 % in the proposed scenarios, with a resolution time of 14 s and using a memory of about 183 MB. The simulations suggest a higher penetration of green hydrogen in scenarios where supply and investment costs decrease to gray hydrogen supply levels, reaching up to 81 % coverage of the thermal demand of the building. Hybrid energy systems under favorable conditions show a penetration of about 92 % within the distributed generation mix. The developed tool could enable decision-makers to optimally plan distributed generation projects in buildings based on economic, policy, and geographic conditions.

Maternal preconception glucose intolerance and fatty acid intake from conception to weaning: impact on offspring energy homeostasis in both male and female.

Environmental factors in the early life stages can lead the descendant to adaptations in gene expression, permanently impacting several structures and organs. The amount and quality of fatty acids in the maternal diet in pregnancy and lactation were found to impact offspring metabolism. So, maternal diet and insulin resistance can affect the male and female descendants through distinct pathways and at different time points. We hypothesized that maternal high-fat diet (HFD) intake before conception and an adequate amount of different fatty acids intake during pregnancy and lactation could influence the energy homeostasis system of 21-day-old offspring. Female rats received control diet (C) or HFD (HF) for 8 weeks before pregnancy. During pregnancy and lactation C group remained with same diet (C-C), HF group were distributed into 4 groups and received C diet (HF-C), normolipidic diet based on saturated fatty acids (HF-S) or based on polyunsaturated fatty acids n-3 (HF-P) or remained in same diet (HF-HF). Maternal HFD in preconception, pregnancy, and lactation (HF-HF) led to lower glucagon-like peptide-1 levels in male (HF-HF21) compared to other groups (C-C21, HF-C21, and HF-P21) and compared to HF-HF21 females. Neuropeptide YY levels were higher in the HF-HF21, HF-C21, and HF-S21 male offspring compared to HF-P21. HF-P21 was similar to C-C21. Positive correlations were found among the energy homeostasis markers genes expressed in the offspring hypothalamus. Maternal diet changes to adequate quantities of fatty acids during pregnancy and lactation showed less impaired results but was not entirely avoided. A maternal diet based on PUFA n-3 during pregnancy and lactation seems to reverse the damage of an HFD in preconception. These results of homeostasis energy system disturbance in the offspring at weaning give us clues about changes that precede the onset of the disease in adult life - adding notes to the knowledge for future investigations of prevention and treatment of chronic diseases.

Neonatal overfeeding promotes anxiety, impairs episodic-like memory, and disrupts transcriptional regulation of hippocampal steroidogenic enzymes.

The objective of our study was to investigate the impact of neonatal overfeeding on cognitive functions and neurosteroidogenesis in male rats. Offspring were assigned to either small litters (SL; 4 pups/mother), resulting in increased milk intake and body weight gain, or normal litters (NL; 10 pups/mother). On postnatal day (PND) 21, half of the male rats were euthanized, while the remaining were kept under standard conditions (4 rats/cage) until PND70. At this stage, subjects underwent assessments for locomotor activity, anxiety levels via the elevated plus maze, and episodic-like memory (ELM) tests. By PND90, the rats were euthanized for brain dissection. Utilizing micropunch techniques, dentate gyrus (DG), CA1, and CA3 regions were extracted for analysis of mRNA expression and methylation patterns. At PND21, SL rats exhibited increased body and adipose tissue weights, alongside elevated cholesterol, glucose, and triglyceride levels compared to NL counterparts. By PND90, although metabolic disparities were no longer evident, SL rats demonstrated heightened anxiety-like behavior and diminished performance in ELM tests. Early life changes included a decreased expression of aromatase (P450arom) and 3α-HSD in CA1, with increased levels in CA3 and DG among SL rats. Additionally, PND90 rats from SL exhibited increased P450arom and decreased 5α-reductase 1 (5αR-1) expression in DG. Notably, some of these variations were correlated with changes in methylation patterns of their promoter regions. Our findings reveal that neonatal overfeeding exerts a long-term adverse effect on cognitive abilities and neurosteroidogenic pathways, underscoring the lasting impact of nutritional experiences during critical early postnatal development periods.

Relevant insights and concepts overlooked throughout the development of flow analysis. A tutorial.

The conceptual expansion, fast development, and general acceptance of flow analysis are consequence of its adherence to the principles of green and white analytical chemistry, and chemical derivatization plays an essential role in this context. Through the flow analysis development, however, some of its potentialities and limitations have been overlooked. This is more evident when the involved modifications in flow rates, timing and/or manifold architecture deteriorate the analytical signals. These aspects have not always been systematically investigated, and are addressed here in relation to flow analyzers with UV-Vis spectrophotometric detection. Novel strategies for solution handling, guidance for dealing with the aforementioned analytical signal deterioration, and an alternative possibility for exploiting differential aspiration are presented. The concept of blank reagent carrier stream is proposed.

Prenatal stress induces sex- and tissue-specific alterations in insulin pathway of Wistar rats offspring.

BACKGROUND AND AIMS: Prenatal stress may lead to tissue and sex-specific cardiometabolic disorders in the offspring through imbalances in the insulin signaling pathway. Therefore, we aimed to determine the sex-specific adaptations of prenatal stress on the insulin signaling pathway of cardiac and hepatic tissue of adult offspring Wistar rats. METHODS: Wistar pregnant rats were divided into control and stress groups. Unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. After lactation, the dams were euthanized and blood was collected for corticosterone measurement and the offspring were separated into four groups according to sex and intervention (n=8/group). At 90 days old, the offspring were submitted to an oral glucose tolerance test (OGTT) and an insulin tolerance test (ITT). After euthanasia blood collection was used for biochemical analysis and the left ventricle and liver were used for protein expression and histological analysis. RESULTS: Stress increased maternal corticosterone levels, and in the offspring, decreased glucose concentration in both OGTT and ITT, reduced insulin receptor (Irß) and insulin receptor substrate-1 (IRS1) activation and reduced insulin receptor inhibition (PTP1B) in the liver of male offspring at 90 days old, without repercussions in cardiac tissue. Moreover, female offspring submitted to prenatal stress exhibited reduced fatty acid uptake, with lower hepatic CD36 expression, reduced high density lipoprotein (cHDL) and increased Castelli risk indexes I and II. CONCLUSIONS: Unpredictable prenatal stress evoked reduced insulin sensitivity and liver-specific impairment in insulin signaling activation in male while increasing markers of cardiovascular risk in females.

The Beneficial Effects of Prenatal Biotin Supplementation in a Rat Model of Intrauterine Caloric Restriction to Prevent Cardiometabolic Risk in Adult Female Offspring.

Numerous studies indicate that intrauterine growth restriction (IUGR) can predispose individuals to metabolic syndrome (MetS) in adulthood. Several reports have demonstrated that pharmacological concentrations of biotin have therapeutic effects on MetS. The present study investigated the beneficial effects of prenatal biotin supplementation in a rat model of intrauterine caloric restriction to prevent cardiometabolic risk in adult female offspring fed fructose after weaning. Female rats were exposed to a control (C) diet or global caloric restriction (20%) (GCR), with biotin (GCRB) supplementation (2 mg/kg) during pregnancy. Female offspring were exposed to 20% fructose (F) in drinking water for 16 weeks after weaning (C, C/F, GCR/F, and GCRB/F). The study assessed various metabolic parameters including Lee's index, body weight, feed conversion ratio, caloric intake, glucose tolerance, insulin resistance, lipid profile, hepatic triglycerides, blood pressure, and arterial vasoconstriction. Results showed that GCR and GCRB dams had reduced weights compared to C dams. Offspring of GCRB/F and GCR/F dams had lower body weight and Lee's index than C/F offspring. Maternal biotin supplementation in the GCRB/F group significantly mitigated the adverse effects of fructose intake, including hypertriglyceridemia, hypercholesterolemia, hepatic steatosis, glucose and insulin resistance, hypertension, and arterial hyperresponsiveness. This study concludes that prenatal biotin supplementation can protect against cardiometabolic risk in adult female offspring exposed to postnatal fructose, highlighting its potential therapeutic benefits.

Nighttime eating during pregnancy and infant adiposity at 6 months of life.

Introduction: Chrononutrition studies the relation between diet, circadian rhythms and metabolism, which may alter the metabolic intrauterine environment, influencing infant fat-mass (FM) development and possibly increasing obesity risk. Aim: To evaluate the association of chrononutrition in pregnancy and infant FM at 6 months. Methods: Healthy pregnant women and term-babies (n = 100pairs) from the OBESO cohort (2017-2023) were studied. Maternal registries included pregestational body-mass-index (BMI), gestational complications/medications, weight gain. Diet (three 24 h-recalls, 1 each trimester) and sleep-schedule (first and third trimesters) were evaluated computing fasting (hours from last-first meal), breakfast and dinner latencies (minutes between wake up-breakfast and dinner-sleep, respectively), number of main meals/day, meal skipping (≥1 main meal/d on three recalls) and nighttime eating (from 9:00 pm-5:59 am on three recalls). Neonatal weight, length, BMI/age were assessed. At 6 months, infant FM (kg, %; air-displacement plethysmography) was measured, and FM index (FMI-kgFM/length2) computed. Exclusive breastfeeding (EBF) was recorded. Multiple linear regression models evaluated the association between chrononutrition and 6 month infant FM. Results: Mean fasting was 11.7 ± 1.3 h; breakfast, dinner latency were 87.3 ± 75.2, 99.6 ± 65.6 min, respectively. Average meals/day were 3.0 ± 0.5. Meal skipping was reported in 3% (n = 3) of women and nighttime eating in 35% (n = 35). Most neonates had normal BMI/age (88%, n = 88). Compared to those who did not, mothers engaged in nighttime-eating had infants with higher %FM (p = 0.019). Regression models (R 2 ≥ 0.308, p ≤ 0.001) showed that nighttime eating was positively associated with %FM (B: 2.7, 95%CI: 0.32-5.16). When analyzing women without complications/medications (n = 80), nighttime eating was associated with higher FM [%FM, B: 3.24 (95%CI: 0.59-5.88); kgFM, B: 0.20 (95%CI: 0.003-0.40); FMI, B: 0.54 (95%CI: 0.03-1.05)]. Infant sex and weight (6 months) were significant, while maternal obesity, pregnancy complications/medications, parity, energy intake, birth-BMI/age, and EBF were not. Conclusion: Maternal nighttime eating is associated with higher adiposity in 6 month infants.

Impact of Parenteral Maternal Supplementation with Trace Minerals and Vitamins on Neonatal Calf Antioxidant System and Growth in a Dairy Herd.

Oxidative stress may affect new born calves due to high stress suffered around birth. We hypothesized that maternal supplementation with micronutrients and vitamins in late gestation enhance the neonatal calf's antioxidant system, decreasing the occurrence and duration of diarrhea, and improving growth from birth through weaning. To test this hypothesis, 80 multiparous cows were cluster-assigned to treatment groups. Treated group (TG) cows received mineral and vitamin supplementation while control group (CG) cows received saline solution. Feed intake and fecal score were measured daily until the ninth week. Weight and body measurements were registered weekly, and blood samples were collected from postpartum cows and calves after birth and at 7, 14, and 63 days of life. Although CG calves had greater fecal scores (p = 0.01), diarrhea characteristics did not differ. Calves in the TG showed greater starter intake (p = 0.04). Feed efficiency showed a trend with treatment-age interaction (p = 0.06). Calves in the CG had wider hips in the first week (p = 0.03), but not by the ninth week. Total antioxidant status, thiobarbituric acid reactive substances, and haptoglobin did not differ between treatment groups. Serum metabolites showed no differences. Supplementation did not impact calf antioxidant system or growth in the first two months.

Prenatal Arsenic Exposure on DNA Methylation of C18ORF8 and ADAMTS9 Genes of Newborns from the POSGRAD Birth Cohort Study.

Exposure to arsenic (As) is a public health problem associated with cancer (skin and colon) and it has been reported that epigenetic changes may be a potential mechanism of As carcinogenesis. It is pertinent to evaluate this process in genes that have been associated with cancer, such as ADAMTS9 and C18ORF8. Gestation and delivery data were obtained from the POSGRAD study. Exposure to As was measured in urine during pregnancy. Gene methylation was performed by sodium bisulfite sequencing; 26 CpG sites for the C18ORF8 gene and 21 for ADAMTS9 were analyzed. These sites are located on the CpG islands near the start of transcription. Sociodemographic characteristics were obtained by a questionnaire. The statistical analysis was performed using multiple linear regression models adjusted for potential confounders. Newborns with an As exposure above 49.4 µg g-1 showed a decrease of 0.21% on the methylation rate in the sites CpG15, CpG19, and CpG21 of the C18ORF8 gene (adjusted ß = -0.21, p-value = 0.02). No statistically significant association was found between prenatal exposure to As and methylation of the ADAMTS9 gene. Prenatal exposure to As was associated with decreased DNA methylation at the CpG15, CpG19, and CpG21 sites of the C18ORF8 gene. These sites can provide information to elucidate epigenetic mechanisms associated with prenatal exposure to As and cancer.

Neurohabilitation of Cognitive Functions in Pediatric Epilepsy Patients through LEGO®-Based Therapy.

In the pediatric population, epilepsy is one of the most common neurological disorders that often results in cognitive dysfunction. It affects patients' life quality by limiting academic performance and self-esteem and increasing social rejection. There are several interventions for the neurohabilitation of cognitive impairment, including LEGO®-based therapy (LEGO® B-T), which promotes neuronal connectivity and cortical plasticity through the use of assembly sets and robotic programming. Therefore, the aim of this study was to analyze the effect of LEGO® B-T on cognitive processes in pediatric patients with epilepsy. Eligible patients were identified; in the treatment group, an initial evaluation was performed with the NEUROPSI and BANFE-2 neuropsychological tests. Then, the interventions were performed once a week, and a final test was performed. In the control group, after the initial evaluation, the final evaluation was performed. An overall improvement was observed in the LEGO® B-T patients, with a significant increase in BANFE-2 scores in the orbitomedial, anterior prefrontal, and dorsolateral areas. In addition, in the gain score analysis, the orbitomedial and memory scores were significantly different from the control group. LEGO® B-T neurohabilitation is a remarkable option for epilepsy patients, who are motivated when they observe improvements.

Genotype-by-gestational thermal environment interaction and its impact on the future performance of tropical composite beef cattle offspring.

With global warming, there are growing challenges for raising taurine and composite beef cattle populations in tropical regions, including elevated temperatures, limited forage availability, parasite infestation, and infectious diseases. These environmental factors can trigger specific physiological responses in the developing fetus, which may have long-term implications on its performance. Therefore, the main objective of this study was to assess the influence of naturally induced thermal stress during the gestation period on the subsequent performance of tropical composite beef cattle progeny. Furthermore, we aimed to investigate the impact of genotype-by-gestational thermal environment interaction (G×Eg) on traits under selection pressure in the breeding population. A total of 157,414 animals from 58 farms located in various Brazilian states were recorded for birth weight (BW), preweaning weight gain (PWG), yearling weight (YW), hip height (HH), scrotal circumference (SC), and days to first calving (DFC). We first applied a linear regression model to the BW data, which revealed that the last 40 d of gestation were suitable for calculating the mean temperature humidity index (THIg). Subsequent regression analyses revealed that for every 10-unit increase in THIg, detrimental effects of approximately 1.13% to 16.34% are expected for all traits evaluated. Genetic parameters were estimated through a reaction norm model using THIg as the environmental descriptor. The posterior means of heritability estimates (SD) were 0.35 (0.07), 0.25 (0.03), 0.31 (0.03), 0.37 (0.01), 0.29 (0.07), and 0.20 (0.09) for the direct effect of BW, PWG, YW, HH, SC, and DFC, respectively. These estimates varied along the range of THIg values, suggesting a variable response to selection depending on the thermal environment during gestation. Genetic correlation estimates between more divergent THIg values were low or negative for YW, PWG, and DFC, indicating that the best-performing individuals at low THIg values may not perform as well at high THIg values and vice versa. Overall, thermal stress during gestation impacts the future performance of beef cattle offspring. Our results indicate the need for developing effective breeding strategies that take into account G×Eg effects and the re-ranking of breeding animals along the THIg scale, particularly for traits such as DFC that are highly sensitive to thermal stress.

With global warming posing increasing challenges in tropical regions, this study aimed to assess the impact of thermal stress during gestation on the performance of composite beef cattle offspring. Environmental factors such as high temperatures, humidity, limited forage availability, and parasite infestation can elicit physiological responses in the developing fetus, affecting its long-term performance and welfare. Using the temperature humidity index (THIg) of the late gestation as a measure of thermal environment, a reaction norm model was applied to analyze the birth weight, preweaning weight gain, yearling weight, hip height, scrotal circumference, and days to first calving (DFC). Results revealed that increasing THIg values were associated with a detrimental effect in these traits. Genotype-by-environment interaction was found to significantly influence trait variability, with DFC showing the strongest effect. Negative genetic correlations were observed between divergent THIg values, suggesting that individuals performing well in mild thermal environments may not excel in high thermal stress conditions. The heritability estimates varied along the THIg scale, indicating that selection response may vary depending on the thermal environment during gestation. These findings emphasize the need for breeding strategies that account for genotype-by-environment effects and consider the impact of thermal stress on cattle performance.

Epigenetic regulation by hypoxia, N-acetylcysteine and hydrogen sulphide of the fetal vasculature in growth restricted offspring: A study in humans and chicken embryos.

Fetal growth restriction (FGR) is a common outcome in human suboptimal gestation and is related to prenatal origins of cardiovascular dysfunction in offspring. Despite this, therapy of human translational potential has not been identified. Using human umbilical and placental vessels and the chicken embryo model, we combined cellular, molecular, and functional studies to determine whether N-acetylcysteine (NAC) and hydrogen sulphide (H2S) protect cardiovascular function in growth-restricted unborn offspring. In human umbilical and placental arteries from control or FGR pregnancy and in vessels from near-term chicken embryos incubated under normoxic or hypoxic conditions, we determined the expression of the H2S gene CTH (i.e. cystathionine γ-lyase) (via quantitative PCR), the production of H2S (enzymatic activity), the DNA methylation profile (pyrosequencing) and vasodilator reactivity (wire myography) in the presence and absence of NAC treatment. The data show that FGR and hypoxia increased CTH expression in the embryonic/fetal vasculature in both species. NAC treatment increased aortic CTH expression and H2S production and enhanced third-order femoral artery dilator responses to the H2S donor sodium hydrosulphide in chicken embryos. NAC treatment also restored impaired endothelial relaxation in human third-to-fourth order chorionic arteries from FGR pregnancies and in third-order femoral arteries from hypoxic chicken embryos. This NAC-induced protection against endothelial dysfunction in hypoxic chicken embryos was mediated via nitric oxide independent mechanisms. Both developmental hypoxia and NAC promoted vascular changes in CTH DNA and NOS3 methylation patterns in chicken embryos. Combined, therefore, the data support that the effects of NAC and H2S offer a powerful mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy. KEY POINTS: Gestation complicated by chronic fetal hypoxia and fetal growth restriction (FGR) increases a prenatal origin of cardiovascular disease in offspring, increasing interest in antenatal therapy to prevent against a fetal origin of cardiovascular dysfunction. We investigated the effects between N-acetylcysteine (NAC) and hydrogen sulphide (H2S) in the vasculature in FGR human pregnancy and in chronically hypoxic chicken embryos. Combining cellular, molecular, epigenetic and functional studies, we show that the vascular expression and synthesis of H2S is enhanced in hypoxic and FGR unborn offspring in both species and this acts to protect their vasculature. Therefore, the NAC/H2S pathway offers a powerful therapeutic mechanism of human translational potential against fetal cardiovascular dysfunction in complicated pregnancy.

Protein supplementation during mid-gestation affects maternal voluntary feed intake, performance, digestibility, and uterine blood flow of beef cows.

This study aimed to assess the impact of protein supplementation and its interaction with calf sex (CS) on the performance, metabolism and physiology of pregnant beef cows. Fifty-two multiparous Zebu beef cows carrying female (n = 22) and male (n = 30) fetuses were used. Cows were individually housed from day 100 to 200 of gestation and randomly assigned to restricted (RES, n = 26) or supplemented (SUP, n = 26) groups. The RES cows were ad libitum fed a basal diet (corn silage + sugarcane bagasse + mineral mixture), achieving 5.5% crude protein (CP), while SUP cows received the same basal diet plus a protein supplement (40% CP, at 3.5 g/kg of body weight). All cows were fed the same diet during late gestation. Differences were declared at p < 0.05. No significant interaction between maternal nutrition and calf sex was found for maternal outcomes (p ≥ 0.34). The SUP treatment increased the total dry matter (DM) intake (p ≤ 0.01) by 32% and 19% at mid- and late-gestation respectively. The total tract digestibility of all diet components was improved by SUP treatment at day 200 of gestation (p ≤ 0.02), as well as the ruminal microbial CP production (p ≤ 0.01). The SUP treatment increased (p ≤ 0.03) the cows' body score condition, ribeye area, the average daily gain (ADG) of pregnant components (PREG; i.e., weight accretion of cows caused by pregnancy) and the ADG of maternal tissues (i.e., weight accretion discounting the gain related to gestation) in the mid-gestation. The SUP cows exhibited a lower maternal ADG (p < 0.01) compared to RES cows in late pregnancy. There was a 24% additional gain (p < 0.01) in the PREG components for SUP cows during late gestation, which in turn improved the calf birthweight (p = 0.05). The uterine arterial resistance and pulsatility indexes (p ≤ 0.01) at mid-gestation were greater for RES cows. In conclusion, protein supplementation during mid-gestation is an effective practice for improving maternal performance, growth of the gravid uterus and the offspring's birth weight.

Fish oil supplementation during pregnancy decreases liver endocannabinoid system and lipogenic markers in newborn rats exposed to maternal high-fat diet.

PURPOSE: Maternal high-fat diet (HF) programs obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), hypertriglyceridemia, and hyperglycemia associated with increased endocannabinoid system (ECS) in the liver of adult male rat offspring. We hypothesized that maternal HF would induce sex specific ECS changes in the liver of newborn rats, prior to obesity onset, and maternal fish oil (FO) supplementation would reprogram the ECS and lipid metabolism markers preventing liver triglycerides (TG) accumulation. METHODS: Female rats received a control (CT) (10.9% fat) or HF (28.7% fat) diet 8 weeks prior to mating and during pregnancy. A subgroup of HF dams received 3% FO supplementation in the HF diet (35.4% fat) during pregnancy (HFFO). Serum hormones and liver TG, ECS, lipid metabolism, oxidative stress and autophagy markers were assessed in male and female newborn offspring. RESULTS: Maternal HF diet increased liver cannabinoid receptor 1 (CB1) in males and decreased CB2 in females, with no effect on liver TG. Maternal FO supplementation reduced liver CB1 regardless of the offspring sex, but reduced TG liver content only in females. FO reduced the liver content of the endocannabinoid anandamide in males, and the content of 2-arachidonoylglycerol in both sexes. Maternal HF increased lipogenic and decreased lipid oxidation markers, and FO induced the opposite regulation in the liver of offspring. CONCLUSION: Prenatal HF and FO differentially modulate liver ECS in the offspring before obesity and MASLD development. These results suggest that maternal nutrition at critical stages of development can modulate the offspring's ECS, predisposing or preventing the onset of metabolic diseases.