title: Hippocampal NR3C1 DNA methylation can mediate part of preconception paternal stress effects in rat offspring.
abstract: Many studies have been shown that maternal stress during pregnancy and in early life period influences offspring in the behavioral and molecular aspects in human and animal models. Recent research has indicated that the environmental condition of males before conception has effects on next generations. We evaluated whether preconception paternal stress (PPS) could influence on hippocampal glucocorticoid receptor gene (GR), (NR3C1) expression, corticosterone response and behavioral outcomes of their offspring. For this purpose, adult male rats were subjected to daily 10min session of forced swimming for 21 consecutive days. Then, two parental breeding groups were formed: stressed father (SF) and non-stressed father (NSF) or control group. 30-day-old pups were tested for anxiety-like behavior by using the elevated plus maze (EPM). Serum corticosterone level was also measured by ELISA. Hippocampal NR3C1 DNA methylation, gene and protein expression were respectively assayed by methylation sensitive restriction enzymes (Real Time PCR), Reverse Transcriptase PCR (RT-PCR) and Western-blotting in all groups. More anxiety-related behavior, serum corticosterone concentration, DNA methylation levels of NR3C1 and lower expression of this gene were significantly observed in paternally stressed pups compared to control pups. As well, molecular changes were more pronounced in male pups compared to female pups. Our results revealed that paternal stress prior to conception has a negative effect on molecular, hormonal and behavioral outcomes in their offspring.
authors.affiliation: Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Neuroscience Research Center, Dept. of Physiology, Iran University of Medical Science, Tehran, Iran. Electronic address: niknazar.somayeh@gmail.com.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Niknazar
authors.affiliation: Neuroscience Research Center, Dept. of Physiology, Iran University of Medical Science, Tehran, Iran. Electronic address: arezo_nahavandi@yahoo.com.
authors.forename: Arezo
authors.initials: A
authors.lastname: Nahavandi
authors.affiliation: Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Ali Asghar
authors.initials: AA
authors.lastname: Peyvandi
authors.affiliation: Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Peyvandi
authors.affiliation: Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Navid Ahmady
authors.initials: NA
authors.lastname: Roozbahany
authors.affiliation: Hearing Disorders Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Department of Anatomical Sciences and Biology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hojjat-Allah
authors.initials: HA
authors.lastname: Abbaszadeh
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
chemical_list: C542344:NR3C1 protein, rat; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003345:Corticosterone
keywords: DNA methylation; Forced swim stress; NR3C1; Offspring; Preconception paternal stress