Chronic maternal methanol inhalation in nonhuman primates (Macaca fascicularis): reproductive performance and birth outcome.
The present study was designed to characterize maternal reproductive performance and early offspring effects following exposure to methanol (MeOH) vapor in a nonhuman primate model. The two-cohort study design used 48 adult female Macaca fascicularis (24/cohort) monkeys exposed to 0, 200, 600, or 1800 ppm MeOH vapor for approximately 2.5 h/day, 7 days/week prior to breeding and throughout pregnancy. Maternal body weight measurement, clinical observations and health assessments were conducted routinely throughout the study. Menstrual cyclicity was monitored during the pre-breeding and breeding periods and timed matings were conducted with nonexposed males. Females were monitored closely during the last month of pregnancy. At birth, infant physical characteristics were measured and a newborn health assessment was conducted. Methanol exposure did not alter menstrual cycles, the number of breedings to conception or conception rate. A total of 34 live-born infants were delivered (control=8, 200 ppm=9, 600 ppm=8, 1800 ppm=9). One female each in the control and 600-ppm group delivered a stillborn infant and a cesarean section (C-section) was required to deliver a hydrocephalic infant who died in utero in the maternal 1800-ppm group. Although not statistically significant, five MeOH-exposed females were C-sectioned due to pregnancy complications such as uterine bleeding and prolonged unproductive labor. These complications were not observed in the control group. The mean length of pregnancy in the MeOH-exposed groups was significantly decreased by 6 to 8 days when compared to controls. There were no MeOH-related effects on offspring birthweight or newborn health status. The consistent reduction in length of pregnancy observed in the MeOH females may reflect a treatment effect on the fetal neuroendocrine system. Given that the fetal hypothalamic--pituitary-adrenal axis controls pregnancy length in most species, these results suggest a modest but significant effect of MeOH on the biochemical events that control the timing of birth.
Burbacher
Thomas M
TM
Department of Environmental and Occupational Health Sciences, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195, USA. tmb@u.washington.edu
Grant
Kimberly S
KS
Shen
Danny D
DD
Sheppard
Lianne
L
Damian
Doris
D
Ellis
Stephen
S
Liberato
Noelle
N
D000280:Administration, Inhalation; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D001724:Birth Weight / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D018811:Maternal Exposure; D008597:Menstrual Cycle / Q000187:drug effects; D000432:Methanol / Q000097:blood / Q000633:toxicity*; D036801:Parturition / Q000187:drug effects; D011247:Pregnancy; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D012997:Solvents / Q000633:toxicity; D013997:Time Factors
D012997:Solvents; D000432:Methanol