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 24 h for 96 h. 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.