Fetal development in the rat following disruption of maternal renal function during pregnancy.
Pregnant Sprague-Dawley rats received subcutaneous injections of mercuric chloride (1-4 mg/kg) on either gestation day 7, 9, 11, or 13 to determine effects of altered maternal renal function on embryonic and fetal development. Maternal renal function, assessed by urinalysis, was markedly disrupted for at least 48 hours after treatment and resulted in decreased maternal body weight gain. Residual effects on maternal kidney weight were evident on GD 21 when the females were killed and the fetuses removed and examined for visceral and skeletal development. We did not observe an increased incidence of malformations in the offspring for exposure on any day of gestation. Maternal exposure to mercuric chloride slightly impaired fetal growth over several gestational exposures periods and changed the pattern of rib formation when exposure occurred early in organogenesis. The extent of the changes could not, however, be related to the immediate degree or duration of altered maternal renal function. Rather, we found correlations between lasting effects of exposure as measured by maternal renal weight on GD 21 and super-numerary lumbar rib induction on GD 7 and 9; while for the relationship with fetal weight, the strongest correlation with maternal kidney weight occurred following exposure on GD 9 (P < 0.01), with weaker correlations (P < 0.10) for GD 7 and 13 exposures. Maternal serum urea was negatively correlated with fetal weight from the GD 7 exposure. This study supports the concept that some specific forms of maternal toxicity may be associated with limited manifestations of developmental toxicity, but, in general, embryonic development was observed to proceed normally in the presence of marked disruptions in maternal renal physiology. Maternal toxicity, especially as routinely measured in developmental toxicity studies, cannot be looked upon as a single disease. Instead, each manifestation must be examined for what it signifies to the physiology and well being of the female and for cause-and-effect relationships with fetal observations. Maternal toxicity and developmental toxicity should not be etiologically linked solely because of their concurrent appearance on the dose-response curve.
Kavlock
R J
RJ
Perinatal Toxicology Branch, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711.
Logsdon
T
T
Gray
J A
JA
D058186:Acute Kidney Injury / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D000818:Animals; D003404:Creatinine / Q000097:blood; D005314:Embryonic and Fetal Development / Q000187:drug effects / Q000502:physiology*; D005260:Female; D005865:Gestational Age; D007668:Kidney / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D008431:Maternal-Fetal Exchange / Q000502:physiology*; D008627:Mercuric Chloride / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D011248:Pregnancy Complications / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014508:Urea / Q000097:blood
D008627:Mercuric Chloride; D014508:Urea; D003404:Creatinine