THRA1/PGC-1α/SIRT3 pathway regulates oxidative stress and is implicated in hypertension of maternal hypothyroid rat offspring.

Many epidemiologic and animal studies have shown that maternal hypothyroidism is associated with an increased risk of hypertension in offspring in later life. In this study, we established a maternal hypothyroidism rat model to explore the underlying mechanism that contributes to elevated blood pressure in adult male offspring of hypothyroid mothers. The levels of thyroid hormones (THs) in the offspring were measured using ELISA kits.

BMA-based Mendelian randomization identifies blood metabolites as causal candidates in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH), a prominent determinant of maternal mortality and morbidity worldwide, is hindered by the absence of efficacious biomarkers for early diagnosis, contributing to suboptimal outcomes. Here, we explored potential causal relationships between blood metabolites and the risk of PIH using Mendelian randomization (MR). We employed a two-sample univariable MR approach to empirically estimate the causal relationships between 249 circulating metabolites and PIH.

Homozygous deleterious variants in the C-terminal of TDRD5 impair spermiogenesis, causing severe oligoasthenoteratozoospermia in humans.

Background: PiRNA pathway factors, including evolutionarily conserved Tudor domain-containing proteins, play crucial roles in suppressing transposons and regulating post-meiotic gene expression. TDRD5 is essential for retrotransposon silencing and pachytene piRNA biogenesis; however, a causal link between TDRD5 variants and human infertility has not yet been established.

Objective: To identify the likely pathogenic variants of TDRD5 in infertile men, characterised by azoospermia or severe oligozoospermia.

YTHDF3 modulates the Cbln1 level by recruiting BTG2 and is implicated in the impaired cognition of prenatal hypoxia offspring.

The "Fetal Origins of Adult Disease (FOAD)" hypothesis holds that adverse factors during pregnancy can increase the risk of chronic diseases in offspring. Here, we investigated the effects of prenatal hypoxia (PH) on brain structure and function in adult offspring and explored the role of the N6-methyladenosine (mA) pathway. The results suggest that abnormal cognition in PH offspring may be related to the dysregulation of the mA pathway, specifically increased levels of YTHDF3 in the hippocampus.

CRISPR/Cas9: implication for modeling and therapy of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a deadly neurological disease with a complicated and variable pathophysiology yet to be fully understood. There is currently no effective treatment available to either slow or terminate it. However, recent advances in ALS genomics have linked genes to phenotypes, encouraging the creation of novel therapeutic approaches and giving researchers more tools to create efficient animal models.

Mendelian randomization study on the causal relationship between leukocyte telomere length and prostate cancer.

Background: Leukocyte telomere length (LTL) is related to prostate cancer (PCa). However, the causal relationship between them remains unknown. This study was aimed at identifying the causal direction between LTL and PCa with Mendelian randomization (MR).

Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis.

Objective: We aim to test whether leukocyte telomere length (LTL) is causally associated with the risk of bipolar disorder (BD) using the Mendelian randomization (MR) method.

Methods: Results of a genome-wide association study (GWAS) conducted with 472,174 individuals of European descent were used to screen for single-nucleotide polymorphisms (SNPs) related with LTL traits. Summary-level data for BD (7,647 cases and 27,303 controls) were obtained from UK Biobank.

Body mass index and the risk of basal cell carcinoma: evidence from Mendelian randomization analysis.

Objective: We aim to test whether body mass index (BMI) is causally associated with the risk of basal cell carcinoma (BCC) using Mendelian randomization (MR) analysis.

Methods: Single-nucleotide polymorphisms (SNPs) associated with four BMI-related traits were screened a genome-wide association study (GWAS) with 681,275, 336,107, 454,884, and 461,460 European-descent individuals, respectively. Summary-level data for BCC (17,416 cases and 375,455 controls) were extracted from UK Biobank.

Mendelian randomization analyses identified bioavailable testosterone mediates the effect of sex hormone-binding globulin on prostate cancer.

Objective: A better knowledge of the hormonal etiology of prostate cancer is essential for its prevention and treatment. The goal of this study was to provide causal estimates of the connection between sex hormone-binding globulin and prostate cancer and investigate the possible mediating function of other modifiable risk indicators.

Methods: We used two-step, two-sample multivariable Mendelian randomization using single-nucleotide polymorphisms as instrumental variables for exposure and mediators.

GDF15 negatively regulates RGS16 to impair hepatic lipid metabolism in male mice offspring conceived by in vitro fertilization.

Objectives: We generated an in vitro fertilization and embryo transfer (IVF-ET) mouse model to investigate the molecular mechanism underlying the abnormal lipid metabolism found in IVF-ET offspring.

Methods: The glucose metabolism levels of offspring were assessed by glucose tolerance test (GTT), insulin tolerance test (ITT), and pyruvate tolerance test (PTT). The lipid metabolism levels were assessed by triglycerides (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C).

Hypothyroidism has a protective causal association with hepatocellular carcinoma: A two-sample Mendelian randomization study.

Objective: Observational studies suggest an association between hypothyroidism and the risk of hepatocellular carcinoma (HCC), but the causality and direction of these effects are still inconclusive. We aim to test whether hypothyroidism is causally associated with the risk of HCC by using Mendelian randomization (MR) analysis.

Methods: Single-nucleotide polymorphisms (SNPs) associated with hypothyroidism were screened a genome-wide association study (GWAS) on 337,159 individuals of European descent (16,376 cases and 320,783 controls).

Mendelian randomization identifies age at menarche as an independent causal effect factor for gestational diabetes mellitus.

Aims: The relationship between age at menarche (AAM) and gestational diabetes mellitus (GDM) risk is still inconclusive. This Mendelian randomization (MR) analysis was used to assess systematically the causal relationship between AAM and GDM risk in human beings.

Materials And Methods: Single-nucleotide polymorphisms associated with AAM, oestradiol levels, sex hormone-binding globulin (SHBG) levels and bioavailable testosterone (BioT) levels were screened via the genome-wide association study enrolling individuals of European descent.

Hypoxia-inducible Factor Regulates Ten-eleven Translocated Methylcytosine Dioxygenase 1-c-Myc Binding Involved in Depression-like Behavior in Prenatal Hypoxia Offspring.

Prenatal hypoxia (PH) is one of the most common adverse stimulation during pregnancy. The brain is fragile in the fetal period and sensitive to hypoxia. The offspring who have experienced PH may be at increased risk of developing neurodevelopmental disorders after birth and various neuropsychiatric diseases after adulthood.

Prenatal hypothyroidism diminished exogenous NO-mediated diastolic effects in fetal rat thoracic aorta smooth muscle via increased oxidative stress.

Maternal hypothyroidism is an important problem of modern healthcare and is reported to increase the risk of cardiovascular diseases in the offspring later in life. However, it is unclear whether hypothyroidism during pregnancy causes vascular damage in the fetal period. We established the prenatal hypothyroidism rat model and collected the fetuses at the 21th day of gestation (GD21).

Gestational exposure to fluoride impairs cognition in C57 BL/6 J male offspring mice via the p-Creb1-BDNF-TrkB signaling pathway.

Fluoride exposure has a detrimental effect on neurodevelopment, while the underlying processes remain unknown. The goal of this study was to investigate how fluoride impacts synaptogenesis, with a focus on the phosphorylation of Creb1 (p-Creb1)-brain-derived neurotrophic factor (BDNF)-tyrosine kinase B (TrkB) pathway. We generated a sodium fluoride (NaF) model using C57 BL/6 J mice exposed to 100 mg/L NaF from gestation day 1 (GD1) to GD20.

Paternal High-Fat Diet Altered Sperm 5'tsRNA-Gly-GCC Is Associated With Enhanced Gluconeogenesis in the Offspring.

Paternal lifestyle, stress and environmental exposures play a crucial role in the health of offspring and are associated with non-genetic inheritance of acquired traits, however the underlying mechanisms are unclear. In this study, we aimed to find out how the sperm tsRNA involved in paternal high-fat diet induced abnormal gluconeogenesis of F1 offspring, and explore the underlying molecular mechanism of its regulation. We generated a paternal high fat diet (42% kcal fat) model to investigate the mechanism by which paternal diet affects offspring metabolism.

Hypo-Hydroxymethylation of Nobox is Associated with Ovarian Dysfunction in Rat Offspring Exposed to Prenatal Hypoxia.

Prenatal hypoxia (PH) is a common feature of a suboptimal intrauterine environment affecting the development of fetuses. Whether PH leads to abnormal ovary development is not yet clear. This study investigated ovarian function in offspring exposed to PH and the potential underlying molecular mechanisms.

Application of CRISPR/Cas9 in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder clinically characterized by cognitive impairment, abnormal behavior, and social deficits, which is intimately linked with excessive β-amyloid (Aβ) protein deposition along with many other misfolded proteins, neurofibrillary tangles formed by hyperphosphorylated tau protein aggregates, and mitochondrial damage in neurons, leading to neuron loss. Currently, research on the pathological mechanism of AD has been elucidated for decades, still no effective treatment for this complex disease was developed, and the existing therapeutic strategies are extremely erratic, thereby leading to irreversible and progressive cognitive decline in AD patients. Due to gradually mental dyscapacitating of AD patients, AD not only brings serious physical and psychological suffering to patients themselves, but also imposes huge economic burdens on family and society.

Methylation-reprogrammed CHRM3 results in vascular dysfunction in the human umbilical vein following IVF-ET†.

Assisted reproductive technology (ART) has been used globally among infertile couples. However, many epidemiological investigations have indicated that ART is associated with a range of long-term adverse health outcomes in offspring, including cardiovascular disease, obesity, and increased plasma lipid levels. Until now, direct evidence has been limited regarding the pathological changes in vascular function in fetuses with ART.

Re-defining the clinicopathological spectrum of neuronal intranuclear inclusion disease.

Background: The rapidly increasing case reports revealed that neuronal intranuclear inclusion disease (NIID) had concomitant other system symptoms besides nervous system symptoms. In this study, we systematically evaluated the symptoms, signs, auxiliary examination, and pathological changes in different systems in NIID patients.

Methods: NIID patients were confirmed by examining GGC repeats in the NOTCH2NLC gene.

Prostaglandin I2 mediates weak vasodilatation in human placental microvessels.

Human placental vessels (HPVs) play important roles in the exchange of metabolites and oxygen in maternal-fetal circulation. Endothelial-derived prostacyclin (prostaglandin I2, PGI2) is a critical endothelial vasodilator in the body. However, the physiological and pharmacological functions of endothelial PGI2 in the human placenta are still unclear.

Prenatal hypoxia attenuated contraction of offspring coronary artery associated with decreased PKCβ Ser phosphorylation and intracellular calcium.

Aims: Prenatal hypoxia (PH) could affect peripheral vascular tone of the offspring, thus increasing the risk of cardiovascular diseases in adult. However, it's still unknown whether functions of coronary arteries (COA) in adult offspring would be influenced by PH. The present study aimed at effects of PH on vascular tone of COA and its related mechanisms.

Brachydactyly type A3 is caused by a novel 13 bp HOXD13 frameshift deletion in a Chinese family.

Brachydactyly type A (BDA) is defined as short middle phalanges of the affected digits and is subdivided into four types (BDA1-4). To date, the molecular cause is unknown. However, there is some evidence that pathogenic variants of HOXD13 could be associated with BDA3 and BDA4.

Comparison of Vascular Responses to Vasoconstrictors in Human Placenta in Preeclampsia between Preterm and Later Term.

Background: Placental blood vessels play important roles in maternal-fetal circulation. Although pathologic mechanisms of preeclampsia are unclear, it is known that placental vascular dysfunction could contribute to pregnant hypertension. However, placental micro-vessel function or dysfunction at preterm has not been investigated.