Effects of indomethacin on spacing of conceptuses within the uterine horn and on fetal and placental growth in the rat

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Abstract
In the rat, as in most other polytocous species, fetuses tend to be relatively evenly spaced along the uterine horn, porhaps to minimize possible effects of local overcrowding on placental function and fetal growth. Here we administered 2 mg of indomethacin, in split doses on day 5 of gestation, in an attempt to disturb evenness of spacing and so reveal local overcrowding effects, if any. The effects on spacing, expressed as the coefficient of deviation of distances between neighboring implants (CVd%) and correlations between fetal and placental weights and distance to neighbors, was examined on day 16 and day 22 of gestation to cover the period of rapid fetal growth. Indomethacin markedly affected evenness of spacing; at day 16, CVd% increased from a control value of 19.2 to 50.8% and at day 22 from 27.5 to 41.2%. Despite the increased variability of spacing and consequent local crowding, including examples of conjoined placentas in the treated rats, there was no evidence that these local factors affected placental growth or weight of individual fetuses. Indomethacin, however, had a general effect on placental and fetal growth. At day 16, mean fetal weights were retarded but by day 22 had caught up to those of control litters, and this was accompanied by significant placental hypertrophy. Collectively, these results show that the uterus has sufficient reserve to cope with relatively uneven spacing of fetuses and have provided a model for examining catch‐up growth of fetuses and accompanying placental changes.