title: Gestational N-hexane inhalation alters the expression of genes related to ovarian hormone production and DNA methylation states in adult female F1 rat offspring.
abstract: Research has revealed that n-hexane can disrupt adult female endocrine functions; however, few reports have focused on endocrine changes in adult F1 females after maternal exposure during gestation. In this study, female Wistar rats inhaled 100, 500, 2500, or 12,500 ppm n-hexane for 4 h daily during their initial 20 gestational days. The F1 female offspring exhibited abnormal oestrus cycles. Compared with the controls, the in vitro-cultured ovarian granulosa cells of the 12,500 ppm group showed significantly reduced in vitro progesterone and oestradiol secretion. Elevated progesterone secretion was observed in the 500 ppm group, and decreased and significantly upregulated mRNA expression of the Star, Cyp11a1, Cyp17a1, and Hsd3b genes was observed in the 12,500 ppm and 500 ppm groups, respectively. The protein expression levels were consistent with the mRNA expression levels. Methylation screening of the promoter regions of these genes was performed using MeDIP-chip and confirmed by methylation-sensitive high-resolution melting (MS-HRM), and the observed methylation state changes of the promoter regions were correlated with the gene expression levels. The results suggest that the hormone levels in the female offspring after gestational n-hexane inhalation correspond to the expression levels and DNA methylation states of the hormone production genes.
authors.affiliation: Department of Pharmaceuticals, Fujian Health College, Fuzhou 350101, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Chenyun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceuticals, Fujian Health College, Fuzhou 350101, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Ni
authors.affiliation: Department of Pharmaceuticals, Fujian Health College, Fuzhou 350101, China.
authors.forename: Suhua
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Wang
authors.affiliation: Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350004, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Lu
authors.affiliation: Union Hospital of Fujian Medical University, Fuzhou 350000, China. Electronic address: huanghuiling08@126.com.
authors.forename: Huiling
authors.initials: H
authors.lastname: Huang
authors.affiliation: Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou 350004, China. Electronic address: wenchang2008@126.com.
authors.forename: Wenchang
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D002478:Cells, Cultured; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects*; D030762:Estrous Cycle / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006107:Granulosa Cells / Q000187:drug effects* / Q000378:metabolism; D006586:Hexanes / Q000633:toxicity*; D018811:Maternal Exposure / Q000009:adverse effects*; D020411:Oligonucleotide Array Sequence Analysis; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011374:Progesterone / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D006586:Hexanes; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; C026385:n-hexane; D011374:Progesterone; C582555:CYP17A1 protein, rat; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme
keywords: DNA methylation; Granulosa cells; MS-HRM; MeDIP-chip; N-hexane; RT-PCR