Parabens inhibit the early phase of folliculogenesis and steroidogenesis in the ovaries of neonatal rats.
Parabens are widely used as anti-microbial agents in the cosmetic and pharmaceutical industries. Recently, parabens have been shown to act as xenoestrogens, a class of endocrine disruptors. In the present study, 55 female pups were given daily subcutaneous injections of methyl-, propyl-, and butyl-paraben or 17beta-estradiol (E2) during neonatal Day 1-7. The ovaries were excised on postnatal Day 8, then fixed and stained with hematoxylin and eosin for histological analysis. The follicles were counted and classified as being in the primordial, early primary, or primary stages. The number of primordial follicles increased while early primary follicles decreased at the high doses of propyl- and butyl-paraben. The levels of anti-Mullerian hormone (AMH) and Foxl2 mRNA increased by propyl- and butyl-parabens whereas kit ligand/stem cell factor (KITL) expression was up regulated only by butyl-paraben. The mRNA levels of StAR and Cyp11a1 were significantly decreased after treatment with methyl-, propyl-, and butyl-parabens. Consistent with its use as a positive control, E2 regulated the expression of KITL, StAR, and Cyp11a1 genes, but surprisingly did not affect AMH and Foxl2 levels. Thus, E2 and parabens had different effects on the regulation of folliculogenic and steroidogenic genes, demonstrating the estrogenic and nonestrogenic properties of parabens in the ovary. Taken together, our data show that parabens stimulated AMH mRNA expression and consequently inhibited the early phase of folliculogenesis in the ovaries of neonatal female rat. The levels of steroidogenic enzymes, indicators of follicle differentiation, appeared to be regulated by parabens through inhibition of their transcriptional repressor, Foxl2.
Laboratory of Veterinary Biochemistry and Molecular Biology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Hyo-Jin
HJ
Ahn
Beum-Soo
BS
An
Eui-Man
EM
Jung
Hyun
H
Yang
Kyung-Chul
KC
Choi
Eui-Bae
EB
Jeung
D000818:Animals; D000831:Animals, Newborn; D054304:Anti-Mullerian Hormone / Q000096:biosynthesis; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects*; D006080:Ovarian Follicle / Q000378:metabolism*; D010226:Parabens / Q000009:adverse effects* / Q000494:pharmacology; D010750:Phosphoproteins / Q000096:biosynthesis; D011310:Preservatives, Pharmaceutical / Q000009:adverse effects* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D019089:Stem Cell Factor / Q000096:biosynthesis; D000098682:Steroidogenic Acute Regulatory Protein
D004967:Estrogens; D051858:Forkhead Transcription Factors; D010226:Parabens; D010750:Phosphoproteins; D011310:Preservatives, Pharmaceutical; D012333:RNA, Messenger; D019089:Stem Cell Factor; D000098682:Steroidogenic Acute Regulatory Protein; D004958:Estradiol; D054304:Anti-Mullerian Hormone; D002786:Cholesterol Side-Chain Cleavage Enzyme