Methoxychlor inhibits growth and induces atresia of antral follicles through an oxidative Stress Pathway

Rupesh K. Gupta, Kimberly P. Miller, Janice K. Babus, Jodi A. Flaws

Research output: Contribution to journalArticle

Abstract

The mammalian ovary contains antral follicles, which are responsible for the synthesis and secretion of hormones that regulate estrous cyclicity and fertility. The organochlorine pesticide methoxychlor (MXC) causes atresia (follicle death via apoptosis) of antral follicles, but little is known about the mechanisms by which MXC does so. Oxidative stress is known to cause apoptosis in nonreproductive and reproductive tissues. Thus, we tested the hypothesis that MXC inhibits growth and induces atresia of antral follicles through an oxidative stress pathway. To test this hypothesis, antral follicles isolated from 39-day-old CD-1 mice were cultured with vehicle control (dimethylsulfoxide [DMSO]), MXC (1-100 μg/ml), or MXC + the antioxidant N-acetyl cysteine (NAC) (0.1-10mM). During culture, growth was monitored daily. At the end of culture, follicles were processed for quantitative real-time polymerase chain reaction of Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT) mRNA expression or for histological evaluation of atresia. The results indicate that exposure to MXC (1-100 μg/ml) inhibited growth of follicles compared to DMSO controls and that NAC (1-10mM) blocked the ability of MXC to inhibit growth. MXC induced follicular atresia, whereas NAC (1-10mM) blocked the ability of MXC to induce atresia. In addition, MXC reduced the expression of SOD1, GPX, and CAT, whereas NAC reduced the effects of MXC on their expression. Collectively, these data indicate MXC causes slow growth and increased atresia by inducing oxidative stress.

Original languageEnglish (US)
Pages (from-to)382-389
Number of pages8
JournalToxicological Sciences
Volume93
Issue number2
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

Methoxychlor
Oxidative stress
Oxidative Stress
Growth
Acetylcysteine
Cysteine
Glutathione Peroxidase
Dimethyl Sulfoxide
Catalase
Antral
Follicular Atresia
Apoptosis
Polymerase chain reaction
Periodicity
Pesticides

Keywords

  • Antral follicles
  • Methoxychlor
  • Ovary
  • Oxidative stress

ASJC Scopus subject areas

  • Toxicology

Cite this

Methoxychlor inhibits growth and induces atresia of antral follicles through an oxidative Stress Pathway. / Gupta, Rupesh K.; Miller, Kimberly P.; Babus, Janice K.; Flaws, Jodi A.

In: Toxicological Sciences, Vol. 93, No. 2, 10.2006, p. 382-389.

Research output: Contribution to journalArticle

Gupta, Rupesh K. ; Miller, Kimberly P. ; Babus, Janice K. ; Flaws, Jodi A. / Methoxychlor inhibits growth and induces atresia of antral follicles through an oxidative Stress Pathway. In: Toxicological Sciences. 2006 ; Vol. 93, No. 2. pp. 382-389.
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abstract = "The mammalian ovary contains antral follicles, which are responsible for the synthesis and secretion of hormones that regulate estrous cyclicity and fertility. The organochlorine pesticide methoxychlor (MXC) causes atresia (follicle death via apoptosis) of antral follicles, but little is known about the mechanisms by which MXC does so. Oxidative stress is known to cause apoptosis in nonreproductive and reproductive tissues. Thus, we tested the hypothesis that MXC inhibits growth and induces atresia of antral follicles through an oxidative stress pathway. To test this hypothesis, antral follicles isolated from 39-day-old CD-1 mice were cultured with vehicle control (dimethylsulfoxide [DMSO]), MXC (1-100 μg/ml), or MXC + the antioxidant N-acetyl cysteine (NAC) (0.1-10mM). During culture, growth was monitored daily. At the end of culture, follicles were processed for quantitative real-time polymerase chain reaction of Cu/Zn superoxide dismutase (SOD1), glutathione peroxidase (GPX), and catalase (CAT) mRNA expression or for histological evaluation of atresia. The results indicate that exposure to MXC (1-100 μg/ml) inhibited growth of follicles compared to DMSO controls and that NAC (1-10mM) blocked the ability of MXC to inhibit growth. MXC induced follicular atresia, whereas NAC (1-10mM) blocked the ability of MXC to induce atresia. In addition, MXC reduced the expression of SOD1, GPX, and CAT, whereas NAC reduced the effects of MXC on their expression. Collectively, these data indicate MXC causes slow growth and increased atresia by inducing oxidative stress.",
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