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4 results on '"Methyltransferase Like 4"'

1. Prenatal diethylhexylphthalate exposure disturbs adult Leydig cell function via epigenetic downregulation of METTL4 expression in male rats

Author

Qiqi Zhu, Shanshan Zhu, Qiyao Li, Chunnan Hu, Chengshuang Pan, Huitao Li, Yang Zhu, Xiaoheng Li, Yunbing Tang, and Ren-shan Ge

Subjects
Methyltransferase Like 4, Testosterone, Prenatal exposure, Diethylhexyl phthalate, Environmental pollution, TD172-193.5, Environmental sciences, GE1-350
Abstract

Prenatal exposure to diethylhexyl phthalate (DEHP) has been linked with a decline in testosterone levels in adult male rats, but the underlying mechanism remains unclear. We investigated the potential epigenetic regulation, particularly focusing on N6-methyladenosine (m6A) modification, as a possible mechanism. Dams were gavaged with DEHP (0, 10, 100, and 750 mg/kg/day) from gestational day 14 to day 21. The male offspring were examined at the age of 56 days. Prenatal DEHP administration at 750 mg/kg/day caused a decline in testosterone concentrations, an elevation in follicle-stimulating hormone, a downregulated expression of CYP11A1 HSD3B2, without affecting Leydig cell numbers. Interestingly, Methyltransferase Like 4 (METTL4), an m6A methyltransferase, was downregulated, while there were no changes in METTL3 and METTL14. Moreover, CYP11A1 showed m6A reduction in response to prenatal DEHP exposure. Additionally, METTL4 expression increased postnatally, peaking in adulthood. Knockdown of METTL4 resulted in the downregulation of CYP11A1 and HSD3B2 and an increase in SCARB1 expression. Furthermore, the increase in autophagy protection in adult Leydig cells induced by prenatal DEHP exposure was not affected by 3-methyladenosine (3MA) treatment, indicating a potential protective role of autophagy in response to DEHP exposure. In conclusion, prenatal DEHP exposure reduces testosterone by downregulating CYP11A1 and HSD3B2 via m6A epigenetic regulation and induction of autophagy protection in adult Leydig cells as a response to DEHP exposure.

Published
2024
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2. Prenatal diethylhexylphthalate exposure disturbs adult Leydig cell function via epigenetic downregulation of METTL4 expression in male rats.

Author

Zhu, Qiqi, Zhu, Shanshan, Li, Qiyao, Hu, Chunnan, Pan, Chengshuang, Li, Huitao, Zhu, Yang, Li, Xiaoheng, Tang, Yunbing, and Ge, Ren-shan

Subjects
PRENATAL exposure, LEYDIG cells, CELL physiology, DIETHYLHEXYL phthalate, EPIGENETICS
Abstract

Prenatal exposure to diethylhexyl phthalate (DEHP) has been linked with a decline in testosterone levels in adult male rats, but the underlying mechanism remains unclear. We investigated the potential epigenetic regulation, particularly focusing on N6-methyladenosine (m6A) modification, as a possible mechanism. Dams were gavaged with DEHP (0, 10, 100, and 750 mg/kg/day) from gestational day 14 to day 21. The male offspring were examined at the age of 56 days. Prenatal DEHP administration at 750 mg/kg/day caused a decline in testosterone concentrations, an elevation in follicle-stimulating hormone, a downregulated expression of CYP11A1 HSD3B2, without affecting Leydig cell numbers. Interestingly, Methyltransferase Like 4 (METTL4), an m6A methyltransferase, was downregulated, while there were no changes in METTL3 and METTL14. Moreover, CYP11A1 showed m6A reduction in response to prenatal DEHP exposure. Additionally, METTL4 expression increased postnatally, peaking in adulthood. Knockdown of METTL4 resulted in the downregulation of CYP11A1 and HSD3B2 and an increase in SCARB1 expression. Furthermore, the increase in autophagy protection in adult Leydig cells induced by prenatal DEHP exposure was not affected by 3-methyladenosine (3MA) treatment, indicating a potential protective role of autophagy in response to DEHP exposure. In conclusion, prenatal DEHP exposure reduces testosterone by downregulating CYP11A1 and HSD3B2 via m6A epigenetic regulation and induction of autophagy protection in adult Leydig cells as a response to DEHP exposure. [Display omitted] • Prenatal exposure to DEHP lowers testosterone levels in adult male rats. • Prenatal DEHP exposure downregulates the expression of METTL4 and CYP11A1. • METTL4 expression increased postnatally. • METTL4 knockdown is associated with steroid metabolism and autophagy. • DEHP reduces testosterone by downregulating CYP11A1 and HSD3B2 via m6A regulation. [ABSTRACT FROM AUTHOR]

Published
2024
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3. Array CGH analysis of a cohort of Russian patients with intellectual disability

Author

Igor N. Lebedev, Giovanni Romeo, Claudio Graziano, Vaidutis Kučinskas, E. N. Tolmacheva, Nataliya N. Chechetkina, Lyudmila P. Nazarenko, Nikolay A. Skryabin, E. A. Sazhenova, A. A. Kashevarova, Olga A. Salyukova, and Pamela Magini

Subjects
Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adolescent, DNA Copy Number Variations, Methyltransferase like 4, Biology, Russia, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Intellectual Disability, Molecular genetics, Intellectual disability, Genetics, medicine, OMIM : Online Mendelian Inheritance in Man, Humans, media_common.cataloged_instance, Copy-number variation, European union, Child, 030304 developmental biology, media_common, Chromosome Aberrations, Comparative Genomic Hybridization, 0303 health sciences, Chromosomes, Human, Pair 11, General Medicine, medicine.disease, Child, Preschool, DECIPHER, Female, Chromosomes, Human, Pair 4, 030217 neurology & neurosurgery, Comparative genomic hybridization
Abstract

The use of array comparative genomic hybridization (array CGH) as a diagnostic tool in molecular genetics has facilitated the identification of many new microdeletion/microduplication syndromes (MMSs). Furthermore, this method has allowed for the identification of copy number variations (CNVs) whose pathogenic role has yet to be uncovered. Here, we report on our application of array CGH for the identification of pathogenic CNVs in 79 Russian children with intellectual disability (ID). Twenty-six pathogenic or likely pathogenic changes in copy number were detected in 22 patients (28%): 8 CNVs corresponded to known MMSs, and 17 were not associated with previously described syndromes. In this report, we describe our findings and comment on genes potentially associated with ID that are located within the CNV regions.

Published
2014
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4. Genome-wide Association Study of Sensory Disturbances in the Inferior Alveolar Nerve after Bilateral Sagittal Split Ramus Osteotomy

Author

Daisuke Kobayashi, Shinya Kasai, Daisuke Nishizawa, Ken-ichi Fukuda, Takashi Kakizawa, Yoshito Takasaki, and Kazutaka Ikeda

Subjects
Male, Genome-wide association study, Genotype, Mandibular Nerve, Osteotomy, Sagittal Split Ramus, Mandibular nerve, Mandible, Methyltransferase like 4, Inferior alveolar nerve, Neuropathic pain, Hypesthesia, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Bilateral sagittal split ramus osteotomy, Polymorphism (computer science), Dysesthesia, medicine, Humans, Paresthesia, 030304 developmental biology, 0303 health sciences, Polymorphism, Genetic, business.industry, Research, Membrane Proteins, Methyltransferases, Anatomy, Hypoesthesia, Nerve injury, DNA-Binding Proteins, Anesthesiology and Pain Medicine, Touch, Molecular Medicine, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Transcription Factors
Abstract

Background Bilateral sagittal split ramus osteotomy (BSSRO) is a common orthognatic surgical procedure. Sensory disturbances in the inferior alveolar nerve, including hypoesthesia and dysesthesia, are frequently observed after BSSRO, even without distinct nerve injury. The mechanisms that underlie individual differences in the vulnerability to sensory disturbances have not yet been elucidated. Methods The present study investigated the relationships between genetic polymorphisms and the vulnerability to sensory disturbances after BSSRO in a genome-wide association study (GWAS). A total of 304 and 303 patients who underwent BSSRO were included in the analyses of hypoesthesia and dysesthesia, respectively. Hypoesthesia was evaluated using the tactile test 1 week after surgery. Dysesthesia was evaluated by interview 4 weeks after surgery. Whole-genome genotyping was conducted using Illumina BeadChips including approximately 300,000 polymorphism markers. Results Hypoesthesia and dysesthesia occurred in 51 (16.8%) and 149 (49.2%) subjects, respectively. Significant associations were not observed between the clinical data (i.e., age, sex, body weight, body height, loss of blood volume, migration length of bone fragments, nerve exposure, duration of anesthesia, and duration of surgery) and the frequencies of hypoesthesia and dysesthesia. Significant associations were found between hypoesthesia and the rs502281 polymorphism (recessive model: combined X2 = 24.72, nominal P = 6.633 × 10−7), between hypoesthesia and the rs2063640 polymorphism (recessive model: combined X2 = 23.07, nominal P = 1.563 × 10−6), and between dysesthesia and the nonsynonymous rs2677879 polymorphism (trend model: combined X2 = 16.56, nomina P = 4.722 × 10−5; dominant model: combined X2 = 16.31, nominal P = 5.369 × 10−5). The rs502281 and rs2063640 polymorphisms were located in the flanking region of the ARID1B and ZPLD1 genes on chromosomes 6 and 3, whose official names are “AT rich interactive domain 1B (SW11 -like)” and “zona pellucida-like domain containing 1”, respectively. The rs2677879 polymorphism is located in the METTL4 gene on chromosome 18, whose official name is “methyltransferase like 4”. Conclusions The GWAS of sensory disturbances after BSSRO revealed associations between genetic polymorphisms located in the flanking region of the ARID1B and ZPLD1 genes and hypoesthesia and between a nonsynonymous genetic polymorphism in the METTL4 gene and dysesthesia.

Published
2013
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