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Di (2-ethylhexyl) phthalate impairs steroidogenesis in ovarian follicular cells of prepuberal mice
- Source :
- Archives of Toxicology. 91:1279-1292
- Publication Year :
- 2016
- Publisher :
- Springer Science and Business Media LLC, 2016.
-
Abstract
- Di (2-ethylhexyl) phthalate (DEHP) is a plasticizer which is widely used in the manufacture of plastics. As a common environmental contaminant and recognized endocrine disrupting chemical, DEHP is able to deregulate the functions of a variety of tissues, including the reproductive system both in males and females. In order to investigate the possible effects of DEHP on the first wave of folliculogenesis, occurring in the mouse ovary postnatally, mice were administered 20 or 40 μg/kg DEHP through intraperitoneal injection at days 5, 10 and 15 post partum (dpp). Following DEHP treatment the gene expression profile of control and exposed ovaries was compared by microarray analyses at 20 dpp. We found that in the exposed ovaries DEHP significantly altered the transcript levels of several immune response and steroidogenesis associated genes. In particular, DEHP significantly decreased the expression of genes essential for androgen synthesis by theca cells including Lhcgr, Cyp17a1, Star and Ldlr. Immunohistochemistry and immune flow cytometry confirmed reduced expression of LHCGR and CYP17A1 proteins in the exposed theca cells. These effects were associated to a significant reduction in ovarian concentrations of progesterone, 17β-estradiol and androstenedione along with a reduction of LH in the serum. Although we did not find a significant reduction of the number of primary, secondary or antral follicles in the DEHP exposed ovaries when compared to controls, we did observe that theca cells showed an altered structure of the nuclear envelope, fewer mitochondria, and mitochondria with a reduced number of cristae. Collectively, these results demonstrate a deleterious effect of DEHP exposure on ovarian steroidogenesis during the first wave of folliculogenesis that could potentially affect the correct establishment of the hypothalamic-pituitary-ovarian axis and the onset of puberty.
- Subjects :
- 0301 basic medicine
endocrine system
medicine.medical_specialty
Health, Toxicology and Mutagenesis
Inbred Strains
Mice, Inbred Strains
Ovary
010501 environmental sciences
Biology
Toxicology
01 natural sciences
Di (2-ethylhexyl) phthalate
Mice
03 medical and health sciences
chemistry.chemical_compound
Ovarian Follicle
Diethylhexyl Phthalate
Internal medicine
Follicular phase
medicine
Folliculogenesis
Pre-puberty mice
Steroidogenesis
Animals
Female
Gene Expression Regulation
Granulosa Cells
Oligonucleotide Array Sequence Analysis
Puberty
Steroids
Androstenedione
Ovarian follicle
0105 earth and related environmental sciences
Settore BIO/17
Phthalate
General Medicine
Antral follicle
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
Theca
Subjects
Details
- ISSN :
- 14320738 and 03405761
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Archives of Toxicology
- Accession number :
- edsair.doi.dedup.....30cc48dc7d2fa6ebe328fa4857df4df2