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Fetal Growth Modified by Natural and Induced Changes in Maternal Reactivity¹

Department of Biology of American University, Sibley Memorial Hospital, Washington, D. C. 20016

Maternal immunological unresponsiveness has usually been demonstrated with adult tissue allografts. Experiments were first directed to the question of whether maternal reactivity to allogeneic conceptuses parallels that of implants of allogeneic tumor. BALB/c female mice parous by C3H males for one to eight litters and challenged with Tumor 70429 of C3H origin showed increasing unresponsiveness with multiparity. A high percentage of progressively growing tumors in highly multiparous females indicates that unresponsiveness does not give way to sensitization. The effects of multiparity on placental and fetal weights in BALB/c females pregnant by C3H males resulted in a continuing decrease in placental weight (indicative of unresponsiveness) through the third pregnancy, but this was followed by a contrasting progressive weight increase indicating sensitization with four or more pregnancies. Syngeneic placentas displayed a similar pattern suggesting that weight changes were not entirely alloantigen dependent and that fetus-specific antigens also alter maternal reactivity. The effects of specific and nonspecific maternal preimmunization and specific parity on placental weights were tested as follows. One group of BALB/c females was immunized against C3H (specific), a second was immunized against DBA/2 (nonspecific), and a third was not immunized. Each of these groups was divided in half and mated to either C3H or DBA/2 males for a first litter; then all were mated to C3H for a second pregnancy. Placental weights were significantly smaller in females that had their first litter by C3H males. A similar experiment with BALB/c x C57BL F₁ females resulted in fewer changes in placental weights. In all instances, maternal reactivity had its major effect upon placental rather than fetal weight. The effect of maternal unresponsiveness upon reproductive capacity was tested by mating BALB/c females to either DBA/2 or C3H males for a first litter and then mating all females to C3H males for a second litter. Second litters were significantly larger when first litters were also sired by C3H males.

¹ Presented at the Symposium "Cancer and Chemistry" as part of the Fourth Conference on Embryonic and Fetal Antigens in Cancer, November 2 to 5, 1975, Charleston, S. C. This investigation was supported by USPHS Research Grant CA 05660 from the National Cancer Institute.