RGD Reference Report - Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model. - Rat Genome Database

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Parabens Accelerate Ovarian Dysfunction in a 4-Vinylcyclohexene Diepoxide-Induced Ovarian Failure Model.

Authors: Lee, Jae-Hwan  Lee, Myeongho  Ahn, Changhwan  Kang, Hee Young  Tran, Dinh Nam  Jeung, Eui-Bae 
Citation: Lee JH, etal., Int J Environ Res Public Health. 2017 Feb 8;14(2). pii: ijerph14020161. doi: 10.3390/ijerph14020161.
RGD ID: 151893505
Pubmed: PMID:28208728   (View Abstract at PubMed)
PMCID: PMC5334715   (View Article at PubMed Central)
DOI: DOI:10.3390/ijerph14020161   (Journal Full-text)

Parabens are widely used preservatives in basic necessities such as cosmetic and pharmaceutical products. In previous studies, xenoestrogenic actions of parabens were reported in an immature rat model and a rat pituitary cell line (GH3 cells). The relationship between parabens and ovarian failure has not been described. In the present study, the influence of parabens on ovarian folliculogenesis and steroidogenesis was investigated. A disruptor of ovarian small pre-antral follicles, 4-vinylcyclohexene diepoxide (VCD, 40 mg/kg), was used to induce premature ovarian failure (POF). Methylparaben (MP, 100 mg/kg), propylparaben (PP, 100 mg/kg), and butylparaben (BP, 100 mg/kg) dissolved in corn oil were treated in female 8-week-old Sprague-Dawley rat for 5 weeks. Estrus cycle status was checked daily by vaginal smear test. Ovarian follicle development and steroid synthesis were investigated through real-time PCR and histological analyses. Diestrus phases in the VCD, PP, and BP groups were longer than that in the vehicle group. VCD significantly decreased mRNA level of folliculogenesis-related genes (Foxl2, Kitl and Amh). All parabens significantly increased the Amh mRNA level but unchanged Foxl2 and Kitlg acting in primordial follicles. VCD and MP slightly increased Star and Cyp11a1 levels, which are related to an initial step in steroidogenesis. VCD and parabens induced an increase in FSH levels in serum and significantly decreased the total number of follicles. Increased FSH implies impairment in ovarian function due to VCD or parabens. These results suggest that VCD may suppress both formation and development of follicles. In particular, combined administration of VCD and parabens accelerated inhibition of the follicle-developmental process through elevated AMH level in small antral follicles.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to organic cyclic compound  IEP 151893505; 151893505propylparaben and butylparabenRGD 
response to organic cyclic compound  IEP 151893505; 151893505Methylparaben and propylparabenRGD 
response to organic cyclic compound  IEP 151893505; 151893505; 151893505; 151893505Methylparaben more ...RGD 

Objects Annotated

Genes (Rattus norvegicus)
Amh  (anti-Mullerian hormone)
Cyp11a1  (cytochrome P450, family 11, subfamily a, polypeptide 1)
Cyp19a1  (cytochrome P450, family 19, subfamily a, polypeptide 1)
Foxl2  (forkhead box L2)
Fshr  (follicle stimulating hormone receptor)
Hsd3b1  (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1)
Kitlg  (KIT ligand)
Star  (steroidogenic acute regulatory protein)


Additional Information