title: Chronic Exposure of Female Mice to an Environmental Level of Perfluorooctane Sulfonate Suppresses Estrogen Synthesis Through Reduced Histone H3K14 Acetylation of the StAR Promoter Leading to Deficits in Follicular Development and Ovulation.
abstract: Perfluorooctane sulfonate (PFOS) at a high dose of 10 mg/kg has been reported to affect the neuroendocrine system and exert toxic effects in rodents. The present study examined the influence of chronic exposure to a low-dose of PFOS (0.1 mg/kg/day) on female reproductive endocrine and function. Herein, we show that adult female mice exposed to PFOS by gavage for 4 months (PFOS-mice) exhibited a prolongation of diestrus without signs of toxic effects. The numbers of mature follicles and corpora luteum were significantly reduced in PFOS-mice with increase of atresic follicles. The levels of serum estrogen (E2) and progesterone at proestrus and diestrus were reduced in PFOS-mice. In comparison with controls, PFOS-mice showed a significant decrease in the levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), and gonadotrophin-releasing hormone, the number of kisspeptin neurons and the level of kiss1 mRNA in anteroventral periventricular nucleus at proestrus but not at diestrus, which could be corrected with the normalization to E2. PFOS-mice did not generate an LH-surge at proestrus, which could be rescued by the application of E2 or kisspeptin-10. Notably, the level of ovarian steroidogenic acute regulatory (StAR) mRNA was decreased in PFOS-mice with the reduction of histone H3K14 acetylation in StAR promoter relative to control mice, whereas the P450scc expression and histone H3K14 acetylation showed no difference between the groups. The present study provides evidence that the chronic exposure to the low-dose of PFOS through selectively reducing histone acetylation of StAR suppresses the biosynthesis of E2 to impair the follicular development and ovulation.
authors.affiliation: *State Key Lab of Reproductive Medicine; Department of Physiology; and.
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Feng
authors.affiliation: *State Key Lab of Reproductive Medicine; Department of Physiology; and.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Physiology; and.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Cao
authors.affiliation: *State Key Lab of Reproductive Medicine; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China.
authors.forename: Yankai
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Physiology; and.
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.affiliation: *State Key Lab of Reproductive Medicine; Department of Physiology; and lingchen@njmu.edu.cn.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
mesh_terms: D000107:Acetylation; D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects; D004958:Estradiol / Q000096:biosynthesis* / Q000097:blood; D030762:Estrous Cycle / Q000187:drug effects; D005260:Female; D005466:Fluorocarbons / Q000633:toxicity*; D006657:Histones / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D010060:Ovulation / Q000187:drug effects*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D011374:Progesterone / Q000097:blood; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D018570:Risk Assessment; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D036401:Toxicity Tests, Chronic; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D017738:Alkanesulfonic Acids; D052244:Endocrine Disruptors; D005466:Fluorocarbons; D006657:Histones; D009479:Neuropeptides; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D004958:Estradiol; C076994:perfluorooctane sulfonic acid
keywords: estrogen (E2); histone acetylation; hypothalamic-pituitary-gonadal (HPG) axis; perfluorooctane sulfonate (PFOS); steroidogenic acute regulatory (StAR)