Methoxychlor reduces estradiol levels by altering steroidogenesis and metabolism in mouse antral follicles in vitro

Mallikarjuna S. Basavarajappa, Zelieann R. Craig, Isabel Hernández-Ochoa, Tessie Paulose, Traci C. Leslie, Jodi A. Flaws

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

The organochlorine pesticide methoxychlor (MXC) is a known endocrine disruptor that affects adult rodent females by causing reduced fertility, persistent estrus, and ovarian atrophy. Since MXC is also known to target antral follicles, the major producer of sex steroids in the ovary, the present study was designed to test the hypothesis that MXC decreases estradiol (E2) levels by altering steroidogenic and metabolic enzymes in the antral follicles. To test this hypothesis, antral follicles were isolated from CD-1 mouse ovaries and cultured with either dimethylsulfoxide (DMSO) or MXC. Follicle growth was measured every 24h for 96h. In addition, sex steroid hormone levels were measured using enzyme-linked immunosorbent assays (ELISA) and mRNA expression levels of steroidogenic enzymes as well as the E2 metabolic enzyme Cyp1b1 were measured using qPCR. The results indicate that MXC decreased E2, testosterone, androstenedione, and progesterone (P4) levels compared to DMSO. In addition, MXC decreased expression of aromatase (Cyp19a1), 17β-hydroxysteroid dehydrogenase 1 (Hsd17b1), 17α-hydroxylase/17,20-lyase (Cyp17a1), 3β hydroxysteroid dehydrogenase 1 (Hsd3b1), cholesterol side-chain cleavage (Cyp11a1), steroid acute regulatory protein (Star), and increased expression of Cyp1b1 enzyme levels. Thus, these data suggest that MXC decreases steroidogenic enzyme levels, increases metabolic enzyme expression and this in turn leads to decreased sex steroid hormone levels.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalToxicology and Applied Pharmacology
Volume253
Issue number3
DOIs
StatePublished - Jun 15 2011

Keywords

  • Antral follicles
  • Metabolic enzymes
  • Methoxychlor
  • Ovary
  • Steroid hormones
  • Steroidogenic enzymes

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

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