Effects on pubertal growth and reproduction in rats exposed to lead perinatally or continuously throughout development.
The reproductive, endocrine, and growth effects of developmental lead exposure were assessed using a rat model in which 0.6% lead acetate (w/v) was administered in the drinking water ad libitum during different developmental periods to determine if lead actions were a result of direct effects of continuous exposure to the metal ion or secondary to disrupted neonatal "endocrine imprinting." Sprague Dawley rats were exposed to lead: (1) from gestational d 5 through birth; (2) during pregnancy and lactation; (3) during lactation only; (4) from birth through adulthood; or (5) from gestational d 5 through adulthood. Lead effects were measured on the development of aspects of the reproductive system, adult sex steroid levels, and growth rates in both male and female animals. The relative weights of male secondary sex organs in adult offspring were not significantly affected in any of the lead-treated groups. In contrast, female pups exposed to lead from birth through adulthood or from gestational day 5 through adulthood were observed to have significantly delayed vaginal opening and disrupted estrus cycling. These effects on female reproductive physiology were not observed in animals where lead exposure was confined only to pregnancy or lactation. Significant suppression of adult mean serum testosterone levels was only observed in male pups exposed to lead continuously from gestational age 5 d throughout life. Lead decreased birth weight in all animals exposed in utero and mean body weights were significantly decreased in all lead-treated groups up to weaning. Analysis of growth curves revealed that all lead-treated groups had significantly reduced growth rates during lactation. However, in addition, in male pups exposed to lead during pregnancy and lactation, from birth or from gestational age 5 d, growth rates were also significantly reduced during puberty. Postpubertal growth rates were unaffected in any lead-treated group. Thus, delayed female reproductive development and suppression of adult male serum testosterone concentration required continuous exposure to the heavy metal. Little evidence was observed for an alteration of "endocrine imprinting" by lead on either reproductive or growth parameters. Exposure during early development (pregnancy and lactation) resulted in no permanent effects in this model other than small (10%) decreases in the body weight of pups postpuberty.
Ronis
M J
MJ
Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock 72205, USA. RonisMartinJ@exchange.uams.edu
Badger
T M
TM
Shema
S J
SJ
Roberson
P K
PK
Shaikh
F
F
D000284:Administration, Oral; D000728:Androgens / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development; D001724:Birth Weight; D001835:Body Weight / Q000187:drug effects; D005260:Female; D013006:Growth Hormone / Q000187:drug effects / Q000502:physiology; D007774:Lactation; D007854:Lead / Q000009:adverse effects*; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012098:Reproduction / Q000187:drug effects*; D012737:Sex Factors; D012741:Sexual Maturation / Q000187:drug effects*
D000728:Androgens; D007854:Lead; D013006:Growth Hormone