Does Methadone Exposure During Avian Development Alter Sex Ratio of Survivors?

Aim: Methadone is commonly used to treat pregnant heroin users and presumed to be safe for developing offspring. An avian model, free of confounding maternal variables, was used to investigate sex differences from methadone exposure during development.
Place and Duration of Study: Studies were conducted at Marist College, Poughkeepsie, NY between June 2012 and May 2013.
Methodology: In the first experiment, methadone in phosphate buffered saline was administered to fertilized eggs at one of two doses (0.458 mg/kg or 1.75 mg/kg) for one of three durations of exposure (Late, Incubation Days 12 to 19; Mid to Late, Days 9 to 19; or Early to Late, Days 5 to 19) with six eggs in each dose x duration condition and six controls (N = 42 eggs). Feathers were taken from eggs with developed embryos from this study for DNA analysis. DNA analysis was not attempted on embryos that had died early in development and decomposed before eggs were opened on Day 20. In a second experiment, methadone (1.00 mg/kg) was administered to eggs from which embryos were sacrificed at four time points during development to investigate growth retardation in methadone exposed embryos as compared with controls. Feathers were taken from randomly selected eggs exposed from Day 8 to Day 19 for sexing (N = 10 exposed and N = 10 controls.
Results: Methadone exposure significantly affected embryo viability. The sex ratio of exposed specimens was 2:1 in favor of females, a departure from the normal 1:1 ratio. The results suggest that most of the embryos that died during incubation were male.
Conclusion: The skewed sex ratio observed in this study suggests a sex difference in mortality from methadone exposure during development.