Abstract
We investigated the relationship between fetal body weight at term (pregnancy day 21) and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal) of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters) of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters) which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right) or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21), reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation) rather than from general growth retardation and that ossification of hindlimb (medial and proximal) phalanges is a good indicator of treatment-induced fetal growth retardation.
Highlights
In developmental toxicity studies, a reduction of average fetal body weight at term is usually considered to result from a substance-induced prenatal growth retardation
The data reported in the present paper indicate that the body weight of full-term rat fetuses is independent of the uterine horn side where the fetus is located and, once litter size is controlled, it is independent of horn size and of relative position of the fetus within the horn
The results clearly demonstrated, that males were slightly heavier than females and that fetal body weight at term was inversely correlated with litter size
Summary
A reduction of average fetal body weight at term is usually considered to result from a substance-induced prenatal growth retardation. The relationship between body weight at term and extent of ossification of the fetal skeleton has not been extensively investigated. A body weight reduction, or a fetus small for gestational age does not necessarily imply that growth retardation pro-. A smaller and lighter fetus, does not necessarily mean that its growth was retarded, or that it is less mature than expected for the gestational age. Bone ossification advances with gestational age, a substanceinduced impairment of calcification of a particular bone is not necessarily secondary to a slower development of the skeleton as a whole
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