Poster #30

Category: Pre-Doctoral/Post-Doctoral Bio-Medical/Basic Science

METHOXYCHLOR AND ITS METABOLITES INHIBIT GROWTH AND INDUCE ATRESIA OF BABOON ANTRAL FOLLICLES

Gupta, R.1, Aberdeen, G.,2 Babus, J.1, Albrecht, E.2, Flaws, J.1

1Toxicology, University of Maryland, Baltimore; 2Obstetrics, Gynecology and Reproductive Sciences, University of Maryland, Baltimore.

Methoxychlor (MXC), an organochlorine pesticide, is used against insects that attack fruits, vegetables, and home gardens.  MXC and its metabolites, mono-OH MXC (Mono-OH) and bis-OH MXC (HPTE), are known to cause atresia (follicle death via apoptosis) in rodents.  Although studies have examined the effects of MXC in rodents, few studies have evaluated the effects of MXC in primates.  Therefore, the present study tested the hypothesis that MXC and its metabolites (Mono-OH and HPTE) inhibit growth and induce atresia of baboon antral follicles.  Antral follicles were isolated from ovaries of normal cycling adult baboons and cultured in supplemental media with vehicle (dimethylsulfoxide; DMSO), MXC (1-100¼g/ml), Mono-OH (0.1-10¼g/ml), or HPTE (0.1-10¼g/ml) for 96 hours.  Growth was monitored at 24 hour intervals in response to MXC and its metabolites.  After culture, follicles were processed for histological evaluation of atresia during which each follicle was rated for atresia on a scale from 1-4 (1-healthy follicle, 2 < 10%, 3 < 10 to 30%, and 4 > 30% pyknotic bodies/follicle).  Differences between treatment groups were analyzed by analysis of variance.  The results indicate that MXC, Mono-OH, and HPTE significantly inhibit antral follicular growth by 96 hours at all the doses compared to DMSO (n-23; p < 0.005).  MXC and its metabolites also increase atresia by 96 hours compared to DMSO.  The mean atresia rating for DMSO-treated follicles was 1.41 + 0.15, while the mean rating for MXC, Mono-OH, and HPTE-treated follicles were 3.92 + 0.08, 3.56 + 0.16, and 4.00 + 0.00 respectively (n=12; < 0.001).  Moreover, adverse effects of MXC and its metabolites on growth and atresia in baboon antral follicles were observed at lower doses than those causing similar effects in rodents.  In conclusion, these data suggest that MXC and its metabolites inhibit growth and induce atresia of antral follicles.  Supported by U54 HD36207, NIH ES12893, Toxicology Training Grant T32 ES07263.