The Effect of Maternal High-Fat or High-Carbohydrate Diet during Pregnancy and Lactation on Cytochrome P450 2D (CYP2D) in the Liver and Brain of Rat Offspring.

Cytochrome P450 2D (CYP2D) is important in psychopharmacology as it is engaged in the metabolism of drugs, neurosteroids and neurotransmitters. An unbalanced maternal diet during pregnancy and lactation can cause neurodevelopmental abnormalities and increases the offspring's predisposition to neuropsychiatric diseases. The aim of the present study was to evaluate the effect of maternal modified types of diet: a high-fat diet (HFD) and high-carbohydrate diet (HCD) during pregnancy and lactation on CYP2D in the liver and brain of male offspring at 28 (adolescent) or 63 postnatal days (young adult). The CYP2D activity and protein level were measured in the liver microsomes and the levels of mRNAs of CYP2D1, 2D2 and 2D4 were investigated both in the liver and brain. In the liver, both HFD and HCD increased the mRNA levels of all the three investigated CYP2D genes in adolescents, but an opposite effect was observed in young adults. The CYP2D protein level increased in adolescents but not in young adults. In contrast, young adults showed significantly decreased CYP2D activity. Similar effect of HFD on the CYP2D mRNAs was observed in the prefrontal cortex, while the effect of HCD was largely different than in the liver (the CYP2D2 expression was not affected, the CYP2D4 expression was decreased in young adults). In conclusion, modified maternal diets influence the expression of individual CYP2D1, CYP2D2 and CYP2D4 genes in the liver and brain of male offspring, which may affect the metabolism of CYP2D endogenous substrates and drugs and alter susceptibility to brain diseases and pharmacotherapy outcome.

Prenatal dexamethasone exposure impaired vascular reactivity in adult male offspring cerebral arteries.

BACKGROUND: Cerebrovascular disease is one of the leading causes of death worldwide. Middle cerebral artery (MCA) is the largest and most complex of cerebral arteries. The prenatal period is a critical time for development, which largely determines lifelong health. Clinically, glucocorticoids (GCs) administration to accelerate preterm fetal lung maturation has become standard practice. Prenatal GCs administration increases cardiovascular risks in offspring, but little is known regarding the side effects on offspring MCA function. OBJECTIVE: We investigated the alterations of MCA reactivity following prenatal GCs administration in postnatal offspring. METHOD AND RESULTS: Pregnant Sprague-Dawley rats received synthetic GCs (dexamethasone, DEX) during the last week of pregnancy, and we examined vascular reactivity, cellular electrophysiology, and gene promoter epigenetic modifications in the male offspring MCA. Our results showed that prenatal DEX exposure increased the sensitivity of offspring MCA to Angiotensin II, which was resulted from the increased Cav1.2 (L-type Ca2+ channels subunit alpha1 C). Mechanistically, prenatal DEX exposure resulted in a transcriptionally active chromatin structure at the Cav1.2 gene promoter by altering histone modifications. This activation led to increased expression of vascular Cav1.2 gene, ultimately resulting in increased MCA contractility in offspring. CONCLUSION: The present study is the first to demonstrate that the adverse effects of prenatal GCs administration on cerebrovascular tone persist into adulthood, providing new insights into developmental origins of cerebrovascular disease.

Placenta-targeted treatment with nMitoQ prevents an endothelin receptor-A pathway cardiac phenotype observed in adult male offspring exposed to hypoxia in utero.

Prenatal hypoxia is associated with enhanced susceptibility to cardiac ischemia-reperfusion (I/R) injury in adult offspring, however, the mechanisms remain to be fully investigated. Endothelin-1 (ET-1) is a vasoconstrictor that acts via endothelin A (ETA) and endothelin B (ETB) receptors and is essential in maintaining cardiovascular (CV) function. Prenatal hypoxia alters the ET-1 system in adult offspring possibly contributing to I/R susceptibility. We previously showed that ex vivo application of ETA antagonist ABT-627 during I/R prevented the recovery of cardiac function in prenatal hypoxia-exposed males but not in normoxic males nor normoxic or prenatal hypoxia-exposed females. In this follow-up study, we examined whether placenta-targeted treatment with a nanoparticle-encapsulated mitochondrial antioxidant (nMitoQ) during hypoxic pregnancies could alleviate this hypoxic phenotype observed in adult male offspring. We used a rat model of prenatal hypoxia where pregnant Sprague-Dawley rats were exposed to hypoxia (11% O2) from gestational days (GD) 15-21 after injection with 100 µL saline or nMitoQ (125 µM) on GD15. Male offspring were aged to 4 mo and ex vivo cardiac recovery from I/R was assessed. Offspring born from hypoxic pregnancies and treated with nMitoQ had increased cardiac recovery from I/R in the presence of ABT-627 compared with their untreated counterparts where ABT-627 prevented recovery. Cardiac ETA levels were increased in males born from hypoxic pregnancies with nMitoQ treatment compared with saline controls (Western blotting). Our data indicate a profound impact of placenta-targeted treatment to prevent an ETA receptor cardiac phenotype observed in adult male offspring exposed to hypoxia in utero.NEW & NOTEWORTHY In this follow-up study, we showed a complete lack of recovery from I/R injury after the application of an ETA receptor antagonist (ABT-627) in adult male offspring exposed to hypoxia in utero while maternal treatment with nMitoQ during prenatal hypoxia exposure prevented this effect. Our data suggest that nMitoQ treatment during hypoxic pregnancies may prevent a hypoxic cardiac phenotype in adult male offspring.

Selection bias in a male-offspring cohort investigating fecundity: is there reason for concern?

STUDY QUESTION: Is there risk of selection bias in etiological studies investigating prenatal risk factors of poor male fecundity in a cohort of young men? SUMMARY ANSWER: The risk of selection bias is considered limited despite a low participation rate. WHAT IS KNOWN ALREADY: Participation rates in studies relying on volunteers to provide a semen sample are often very low. Many risk factors for poor male fecundity are associated with participation status, and as men with low fecundity may be more inclined to participate in studies of semen quality, a risk of selection bias exists. STUDY DESIGN, SIZE, DURATION: A population-based follow-up study of 5697 young men invited to the Fetal Programming of Semen Quality (FEPOS) cohort nested within the Danish National Birth Cohort (DNBC), 1998-2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Young men (age range: 18 years, 9 months to 21 years, 4 months) born 1998-2000 by mothers included in the DNBC were invited to participate in FEPOS. In total, 1173 men answered a survey in FEPOS (n = 115 participated partly); of those, 1058 men participated fully by also providing a semen and a blood sample at a clinical visit. Differential selection according to parental baseline characteristics in the first trimester, the sons' own characteristics from the FEPOS survey, and urogenital malformations and diseases in reproductive organs from the Danish registers were investigated using logistic regression. The influence of inverse probability of selection weights (IPSWs) to investigate potential selection bias was examined using a predefined exposure-outcome association of maternal smoking in the first trimester (yes, no) and total sperm count analysed using adjusted negative binomial regression. A multidimensional bias analysis on the same association was performed using a variety of bias parameters to assess different scenarios of differential selection. MAIN RESULTS AND THE ROLE OF CHANCE: Participation differed according to most parental characteristics in first trimester but did not differ according to the prevalence of a urogenital malformation or disease in the reproductive organs. Associations between maternal smoking in the first trimester and male fecundity were similar when the regression models were fitted without and with IPSWs. Adjusting for other potential risk factors for poor male fecundity, maternal smoking was associated with 21% (95% CI: -32% to -9%) lower total sperm count. In the bias analysis, this estimate changed only slightly under realistic scenarios. This may be extrapolated to other exposure-outcome associations. LIMITATIONS, REASONS FOR CAUTION: We were unable to directly assess markers of male fecundity for non-participants from, for example an external source and therefore relied on potential proxies of fecundity. We did not have sufficient power to analyse associations between prenatal exposures and urogenital malformations. WIDER IMPLICATIONS OF THE FINDINGS: The results are reassuring when using this cohort to identify causes of poor male fecundity. The results may be generalized to other similar cohorts. As the young men grow older, they can be followed in the Danish registers, as an external source, to examine, whether participation is associated with the risk of having an infertility diagnosis. STUDY FUNDING/COMPETING INTEREST(S): The project was funded by the Lundbeck Foundation (R170-2014-855), the Capital Region of Denmark, Medical doctor Sofus Carl Emil Friis and spouse Olga Doris Friis's Grant, Axel Muusfeldt's Foundation (2016-491), AP Møller Foundation (16-37), the Health Foundation, Dagmar Marshall's Fond, Aarhus University and Independent Research Fund Denmark (9039-00128B). The authors declare that they have no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.

Could parental high-fat intake program the reproductive health of male offspring? A review.

High-fat diet (HFD) intake can cause overweight and obesity and has become a global public health concern in recent years. Nutritional adversity at vulnerable windows of development can affect developing cells and their functions, including germ cells. Evidence shows that parental HFD intake prior to conception and/or during gestation and lactation could program the reproductive health of male offspring, ultimately resulting in impairment of the first as well as subsequent generations. In male offspring, adipose tissue and hypothalamic-pituitary-gonadal axis imbalance can impair the production of gonadotropins, leading to dysfunction of testosterone production and pubertal onset. The gonads can be directly impaired through oxidative stress, causing poor testosterone production and spermatogenesis; low sperm count, viability, and motility; and abnormal sperm morphology, which results in low sperm quality. Parental HFD intake could also be a risk factor for prostate hyperplasia and cancer in advanced age. It can impact the reproductive pattern of male offspring resulting in impairments in the subsequent generations. The investigation of semen quality must be extended to epidemiological and clinical studies of the male offspring of overweight and/or obese parents in order to improve the quality of human semen. This review addresses the effects of parental HFD intake on the reproductive parameters of male offspring and discusses the possible underlying mechanisms.

Paternal alcohol consumption has intergenerational consequences in male offspring.

PURPOSE: Alcoholism is a heterogeneous set of disorders caused by ethanol intake. Harmful effects of paternal consumption on the offspring are poorly explored and not fully understood. We analyzed the effect of paternal alcohol consumption on both their own reproductive capacity and that of their male offspring. METHODS: We used a model of ethanol consumption (15% v/v in drinking water) for 12 days in adult CF-1 male mice. DNA integrity and post-translational modifications of histones were assessed in sperm; testicular weight, histology, and DNA fragmentation were analyzed. Treated or untreated male mice were mated with non-treated females to obtain two cell embryos that were cultured for 7 days; morphology and embryonic cell death were evaluated. Males of both groups were mated with non-treated females. Adult male offspring was euthanized, and sperm and testicular parameters determined. RESULTS: Paternal ethanol consumption caused histological and epigenetic changes, as well as damage in DNA integrity in the testicular germline and sperm. These alterations gave rise to deleterious effects on embryonic development and to testicular and spermatic changes in the offspring. CONCLUSION: This study provides critical information on reproductive disturbances brought about by paternal alcohol consumption and the profound impact these could have on the male progeny. The need to explore the effects of paternal alcohol consumption in detail and warn about the importance of controlling alcohol intake for the well-being of future generations should not be underscored.

Maternal pre-pregnancy overweight and infertility in sons and daughters: A cohort study.

INTRODUCTION: Overweight and obesity in pregnancy is increasing worldwide and may harm the developing fetus, including its future reproductive health. We therefore studied the association between in utero exposure to maternal overweight and obesity and infertility in adulthood. No studies have previously assessed this association. MATERIAL AND METHODS: We performed a cohort study with 9232 adult sons and daughters whose mothers were enrolled in the Danish Healthy Habits for Two cohort during pregnancy in 1984-87. Participants were sons and daughters followed in the Danish In-Vitro-Fertilization-Register and Danish National Patient Register until February 2018 for diagnoses of infertility. RESULTS: In total, 1203 (13%) sons and daughters were born to mothers with a body mass index (BMI) >25 kg/m2 ; 871 (9.4%) of the participants were identified as being infertile during follow-up. Sons of overweight mothers had slightly increased odds of infertility compared with sons of mothers with normal body weight (BMI 18.5-24.9 kg/m2 , adjusted odds ratio 1.4, 95% confidence interval [CI] 1.0-1.9). Cubic spline analyses with continuous BMI levels showed increasing odds with higher levels of BMI; however, for BMI >29 kg/m2 the confidence intervals were too wide to draw conclusions. No association between maternal overweight and infertility was found among daughters (adjusted odds ratio 0.9, 95% CI 0.7-1.2)). CONCLUSIONS: Sons born to overweight mothers had higher odds of infertility compared with sons of normal weight mothers. No association between maternal overweight and infertility was observed in daughters. Prevention of overweight during pregnancy may be an important tool to preserve fecundity in future generations.

Effects of Fetal Exposure to Heat-Not-Burn Tobacco on Testicular Function in Male Offspring.

Several studies show that maternal conventional cigarette smoking during pregnancy has been associated with reduced sperm concentration in sons. The development of heat-not-burn (HnB) tobacco has gained a growing following. However, the effects of prenatal HnB tobacco smoking on male offspring are as yet unknown. Pregnant CD-1 mice were exposed to I-Quit-Ordinary-Smoking (IQOS) (HnB tobacco) aerosol from heat sticks, mainstream smoke from 3R4F (conventional cigarettes) or clean air, using a whole-body exposure system. Adult male offspring mice were divided into six groups: control (5- and 15-weeks-old offspring), IQOS (5 and 15-weeks-old) and 3R4F (5 and 15-weeks-old). Spermatogenesis, sperm characteristics, serum testosterone, and seminiferous tubule morphology were evaluated. Prenatal IQOS exposure increased abnormal seminiferous tubule morphology and decreased sperm production at 5 weeks, but 3R4F exposure did not. Prenatal exposure to IQOS aerosol delays sexual maturation of male offspring or adversely affects the male testicular function of the offspring more than smoke from a combustion cigarette.

piRNA-DQ722010 contributes to prostate hyperplasia of the male offspring mice after the maternal exposed to microcystin-leucine arginine.

BACKGROUND: Microcystin-leucine arginine (MC-LR) could disrupt prostate development and cause prostate hyperplasia. But whether and how maternal and before-weaning MC-LR exposure causes prostate hyperplasia in male offspring by changing expression profile of P-element-induced wimpy (PIWI)-interacting RNAs (piRNAs) have not yet been reported. METHODS: From the 12th day in the embryonic period to the 21st day after offspring birth, three groups of pregnant mice that were randomly assigned were exposed to 0, 10, and 50 µg/L of MC-LR through drinking water followed by the analyses of their male offspring. Abortion rate and litter size of maternal mice were recorded. The prostate histopathology was observed. Differential expressed piRNAs of prostate were screened by piRNA microarray analysis. Murine prostate cancer cell line (RM-1) was used for further mechanism study. Luciferase report assay was used to determine the relationship between piRNA-DQ722010 and polypeptide 3 (Pik3r3). RESULTS: The downregulated expression of piRNA-DQ722010 was the most significant in piRNA microarray analysis in 10 µg/L MC-LR treated group, while Pik3r3 was significantly upregulated, consistent with the results that a distinct prostatic epithelial hyperplasia was observed and phosphoinositide-3-kinase (PI3K)/protien kinase B (AKT) signaling pathway was activated. Pik3r3 was verified as the target gene of piRNA-DQ722010. In addition, we found MC-LR decreased the expression of PIWI-like RNA-mediated gene silencing 2 (Piwil2) and 4 (Piwil4) both in vivo and in vitro, and both Piwil4 and Piwil2 could regulate the expression of DQ722010. CONCLUSION: MC-LR caused downregulation of piRNA-DQ722010 and PIWI proteins, while piRNA-DQ722010 downregulation promoted activation of PI3K/AKT signaling pathway inducing prostate hyperplasia by upregulating the expression of Pik3r3. In contrast, piRNA-DQ722010 downregulation may be attributed to PIWI proteins downregulation.

Effect of in utero and lactational exposure of triazophos on reproductive system functions in male offsprings, Rattus norvegicus.

In the present study, Triazophos (TZ) was used at acceptable daily intake (ADI) to investigate the consequence of prenatal and postnatal exposure on reproductive functions in the male offsprings. Pregnant females were divided into three groups, the first group was orally gavaged with olive oil (control), the second group was administered with 0.01 mg kg-1 bw of the ADI of TZ from gestation day (GD) 1 until parturition (designated as P group) and the third group was gavaged with the same dose from GD1 to postnatal day (PND) 21 of lactation (marked as P + L group). Non-significant reduction occurred in the body weight of pups except at (PND) 35 during which body weight of P + L group pups significantly decreased. Male offsprings born to TZ exposed females showed significant changes at maturity (PND 63) in weight of liver, thyroid and testis, alterations in the levels of protein, urea, creatinine in plasma and abnormal levels of cholesterol, phospholipids and lipid peroxidation in testicular homogenate. Gonadal inhibition in TZ exposed progeny was reflected from a significant fall in sperm count, sperm motility, plasma testosterone level and histopathological alterations in testis. Hence, in utero and lactational exposure to ADI level of TZ influences testis development and functions in the male offsprings. Further investigations are suggested with germline studies of offsprings to examine the transgenerational effect of TZ exposure.

Prenatal Stimulation of 5-HT1A Receptors Improves Adaptive Behavior in Prenatally Stressed Rats.

Various types of adaptive behavior during the prepubertal period were analyzed in the offspring of rats receiving chronic injections of serotonin (5-HT) reuptake inhibitor fluoxetine, 5-HT1A receptor agonist buspirone, or their combination starting from gestation day 9 and subjected to immobilization stress from the 15th day of pregnancy until delivery. Prenatal stress increased pain sensitivity, prolonged inflammatory pain response, and increased the levels of anxiety and depression. Chronic administration of drugs acting through 5-HT1A receptors to pregnant rats improved the studied behavioral parameters in their offspring. Differences in the pain sensitivity were found between the effect of drug combination and each of them separately, and in the level of depression between combined administration and fluoxetine alone.

Mesoporous silica nanoparticle is comparatively safer than zinc oxide nanoparticle which can cause profound steroidogenic effects on pregnant mice and male offspring exposed in utero.

The increasing use of nanomaterials has naturally caused heightened concerns about their potential risks to human and animal health. We investigated the effect of zinc oxide nanoparticles (ZnO NPs) and mesoporous silica nanoparticles (MSN) on steroidogenesis in the corpus luteum (CL) of pregnant mice and testis of male offspring. Pregnant albino mice were exposed to ZnO NPs and MSN for 2 days on alternate days, gestation days 15-19. Hepatic injury marker enzymes increased in the higher concentration of NM-exposed mother mice, but histological examination revealed no changes in the placenta of pregnant mice, whereas testis of male offspring showed gross pathological changes. The expression pattern of progesterone biosynthesis-related genes was also altered in the CL of NP-exposed pregnant mice. In utero exposure of ZnO NPs increased the relative expression of StAR in 100 mg/kg body weight (BW) ZnO NP-treated and bulk ZnO-treated groups and P450 side-chain cleavage enzyme (P450scc) in 50 mg/kg BW ZnO NP-treated and 100 mg/kg of bulk ZnO-treated male offspring. Serum testosterone concentration significantly increased in the 100 mg/kg of bulk ZnO-treated group and decreased in the 250 mg/kg of MSN-treated group and a single dose of 300 mg/Kg BW of ZnO NPs caused miscarriages and adversely affected the developing foetus in mice.

Transgenerational effects of paternal heroin addiction on anxiety and aggression behavior in male offspring.

BACKGROUND: Heroin addiction is a growing concern, affecting the socioeconomic development of many countries. Little is known about transgenerational effects on phenotype changes due to heroin addiction. This study aims to investigate changes in level of anxiety and aggression up to four different generations of adult male rats due to paternal exposure to heroin. METHODS: Male Sprague-Dawley rats were exposed with heroin intraperitoneally (i.p.) twice-daily for 14 days with increasing dosage regimen (F0-heroin). Male Sprague-Dawley rats (6-weeks-old) were divided into: (1) heroin exposed group (F0-heroin) and (2) control group treated with saline solution (F0-control). The dosage regime started with the lowest dose of 3 mg/kg per day of heroin followed by 1.5 mg/kg increments per day to a final dose of 13.5 mg/kg per day. Offspring were weaned on postnatal day 21. The adult male offspring from each generation were then mated with female-naïve rats after 2 weeks of heroin absence. Open field test and elevated plus maze test were used to study the anxiety level, whereas resident intruder test was used to evaluate aggression level in the addicted male rats and their offspring. RESULTS: Heroin exposure in male rats had resulted in smaller sizes of the litters compared to the control. We observed a higher anxiety level in the F1 and F2 progenies sired by the heroin exposed rats (F0) as compared to the control rats. Paternal heroin exposure also caused significantly more aggressive offspring in F1 compared to the control. The same pattern was also observed in the F2. CONCLUSION: Our results demonstrated that the progenies of F1 and F2 sustained higher levels of anxiety and aggression which are due to paternal heroin exposure.

Maternal Food Restriction during Pregnancy and Lactation Adversely Affect Hepatic Growth and Lipid Metabolism in Three-Week-Old Rat Offspring.

Maternal malnutrition influences the early development of foetal adaptive changes for survival. We explored the effects of maternal undernutrition during gestation and lactation on hepatic growth and function. Sprague-Dawley rats were fed a normal or a food-restricted (FR) diet during gestation and/or lactation. We performed analyses of covariance (adjusting for the liver weight/body weight ratio) to compare hepatic growth and lipid metabolism among the offspring. Maternal FR during gestation triggered the development of wide spaces between hepatic cells and increased the expression of mammalian target of rapamycin (mTOR) in three-week-old male offspring compared with controls (both p < 0.05). Offspring nursed by FR dams exhibited wider spaces between hepatic cells and a lower liver weight/body weight ratio than control offspring, and increased mTOR expression (p < 0.05). Interestingly, the significant decrease in expression of lipogenic-related genes was dependent on carbohydrate-responsive element-binding protein, despite the increased expression of sterol regulatory element-binding protein 1 (SREBP1) (p < 0.05). This study demonstrated increased expression of key metabolic regulators (mTOR and SREBP1), alterations in lipid metabolism, and deficits in hepatic growth in the offspring of FR-treated dams.

Maternal nutrition and fetal imprinting of the male progeny.

The global population as well as the demand for human food is rapidly growing worldwide, which necessitates improvement of efficiency in livestock operations. In this context, environmental factors during fetal and/or neonatal life have been observed to influence normal physical and physiological function of an individual during adulthood, and this phenomenon is called fetal or developmental programming. While numerous studies have reported the impact of maternal factors on development of the female progeny, limited information is available on the potential effects of fetal programming on reproductive function of the male offspring. Therefore, the objective for this review article was to focus on available literature regarding the impact of maternal factors, particularly maternal nutrition, on reproductive system of the male offspring. To this end, we highlighted developmental programming of the male offspring in domestic species (i.e., pig, cow and sheep) as well as laboratory species (i.e., mice and rat) during pregnancy and lactation. In this sense, we pointed out the effects of maternal nutrition on various functions of the male offspring including hypothalamic-pituitary axis, hormonal levels, testicular tissue and semen parameters.

Gestational Hypoxia Impaired Endothelial Nitric Oxide Synthesis Via miR-155-5p/NADPH Oxidase/Reactive Oxygen Species Axis in Male Offspring Vessels.

BACKGROUND: Nitric oxide (NO) is the most important vasodilator secreted by vascular endothelial cells, and its abnormal synthesis is involved in the development of cardiovascular disease. The prenatal period is a critical time for development and largely determines lifelong vascular health in offspring. Given the high incidence and severity of gestational hypoxia in mid-late pregnancy, it is urgent to further explore whether it affects the long-term synthesis of NO in offspring vascular endothelial cells. METHODS AND RESULTS: Pregnant Sprague-Dawley rats were housed in a normoxic or hypoxic (10.5% O2) chamber from gestation days 10 to 20. The thoracic aortas of fetal and adult male offspring were isolated for experiments. Gestational hypoxia significantly reduces the NO-dependent vasodilation mediated by acetylcholine in both the fetal and adult offspring thoracic aorta rings. Meanwhile, acetylcholine-induced NO synthesis is impaired in vascular endothelial cells from hypoxic offspring thoracic aortas. We demonstrate that gestational hypoxic offspring exhibit a reduced endothelial NO synthesis capacity, primarily due to increased expression of NADPH oxidase 2 and enhanced reactive oxygen species. Additionally, gestational hypoxic offspring show elevated levels of miR-155-5p in vascular endothelial cells, which is associated with increased expression of NADPH oxidase 2 and reactive oxygen species generation, as well as impaired NO synthesis. CONCLUSIONS: The present study is the first to demonstrate that gestational hypoxia impairs endothelial NO synthesis via the miR-155-5p/NADPH oxidase 2/reactive oxygen species axis in offspring vessels. These novel findings indicate that the detrimental effects of gestational hypoxia on fetal vascular function can persist into adulthood, providing new insights into the development of vascular diseases.

Altered baroreflex sensitivity at rest and during Valsalva maneuver in healthy male offspring of hypertensive patients.

INTRODUCTION: A family history of hypertension puts young adults at a higher risk of developing hypertension, that too, at an earlier age than their parents. Recent studies suggest that the baroreflex mechanism, which takes care of the short-term regulation of blood pressure (BP), also plays a role in the long-term regulation of BP. Studies have reported decreased baroreflex sensitivity (BRS) in hypertensives. Reduced BRS is shown to herald the future occurrence of cardiovascular diseases (CVD) and helps in risk stratification AIM: To assess BRS at rest and during the Valsalva maneuver among apparently healthy male offspring (age 18-35 years) of hypertensive patients. METHODS: We recruited 37 participants whose parents (either/both) were hypertensive in the study group and whose parents (both) were not hypertensive in the control group. We measured basic anthropometric parameters (height, weight, waist circumference), cardiovascular parameters (heart rate and BP), short-term heart rate variability, and BRS (at rest and during Valsalva). RESULTS: We found that BRS at rest and BRS during the Valsalva maneuver were reduced among healthy male offspring of hypertensive parents than in healthy male offspring of non-hypertensive parents. Further, HRV indices and Valsalva ratio showed a sympathovagal imbalance in the form of decreased vagal and increased sympathetic activity. CONCLUSION: The reduced BRS and sympathovagal imbalance in male offspring of hypertensive parents reveal the early risk of developing hypertension in the future.

Gestational administration of vitamin D improves maternal care and prevents anxiety-like behavior in male and female Wistar rats prenatally exposed to dexamethasone.

Prenatal overexposure to glucocorticoids (GC) can lead to behavioral changes in adulthood. We aimed to explore the effects of gestational administration of vitamin D on the behavioral responses of dams and their offspring prenatally exposed to dexamethasone (DEX). Vitamin D (500UI) was given daily during the whole pregnancy (VD group). Half of the groups that received vitamin D were treated with DEX (0.1 mg/kg, VD + DEX group) daily between the 14th and 19th days of pregnancy. The corresponding control groups of progenitors were assigned (CTL and DEX groups, respectively). Maternal care and the dam's behaviors were evaluated during lactation. The offspring had developmental and behavioral parameters evaluated during lactation and at 3, 6, and 12 months of age. Gestational administration of vitamin D increased maternal care and had an anxiolytic-like effect on the dams, but the latter was blocked in DEX-treated dams. Prenatal DEX partially impaired neural development and caused an anxiety-like phenotype in the male and female offspring at 6 months, which was prevented by gestational administration of vitamin D. As well, gestational vitamin D improved memory just in the male offspring, but this response was suppressed by prenatal DEX. We concluded that gestational vitamin D could prevent anxiety-like behavior in adult male and female rats prenatally exposed to DEX, which might be, in part, a result of the maternal care improvement.

Transgenerational transmission of reproductive and metabolic dysfunction in the male progeny of polycystic ovary syndrome.

The transgenerational maternal effects of polycystic ovary syndrome (PCOS) in female progeny are being revealed. As there is evidence that a male equivalent of PCOS may exists, we ask whether sons born to mothers with PCOS (PCOS-sons) transmit reproductive and metabolic phenotypes to their male progeny. Here, in a register-based cohort and a clinical case-control study, we find that PCOS-sons are more often obese and dyslipidemic. Our prenatal androgenized PCOS-like mouse model with or without diet-induced obesity confirmed that reproductive and metabolic dysfunctions in first-generation (F1) male offspring are passed down to F3. Sequencing of F1-F3 sperm reveals distinct differentially expressed (DE) small non-coding RNAs (sncRNAs) across generations in each lineage. Notably, common targets between transgenerational DEsncRNAs in mouse sperm and in PCOS-sons serum indicate similar effects of maternal hyperandrogenism, strengthening the translational relevance and highlighting a previously underappreciated risk of transmission of reproductive and metabolic dysfunction via the male germline.

A primary study on rat fetal development and brain-derived neurotrophic factor levels under the control of electromagnetic fields.

Background: In previous researches, electromagnetic fields have been shown to adversely affect the behavior and biology of humans and animals; however, body growth and brain-derived neurotrophic factor levels were not evaluated. Objective: The original investigation aimed to examine whether Electromagnetic Fields (EMF) exposure had adverse effects on spatial learning and motor function in rats and if physical activity could diminish the damaging effects of EMF exposure. In this study, we measured anthropometric measurements and brain-derived neurotrophic factor (BDNF) levels in pregnant rats' offspring to determine if Wi-Fi EMF also affected their growth. These data we report for the first time in this publication. Methods: Twenty Albino-Wistar pregnant rats were divided randomly into EMF and control (CON) groups, and after delivery, 12 male fetuses were randomly selected. For assessing the body growth change of offspring beginning at delivery, then at 21 postnatal days, and finally at 56 post-natal days, the crown-rump length of the body was assessed using a digital caliper. Examining BDNF factor levels, an Enzyme-linked immunosorbent assay ELISA kit was taken. Bodyweight was recorded by digital scale. Results: Outcomes of the anthropometric measurements demonstrated that EMF blocked body growth in rats exposed to EMF. The results of the BDNF test illustrated that the BDNF in the EMF liter group was remarkably decreased compared to the CON group. The results indicate that EMF exposure could affect BDNF levels and harm body growth in pregnant rats' offspring. Conclusions: The results suggest that EMF exposure could affect BDNF levels and impair body growth in pregnant rats' offspring.