Physiology&Behavior, Vol. 55, pp. 35-38, 1994 0031-9384/94 $6.00 + .00 Printed in the USA. Copyright© 1993PergamonPressLtd. Estrogen Antibodies Reduce Vulnerability to Stress-Induced Failure of Intrauterine Implantation in Inseminated Mice DENYS DECATANZARO, t ELAINE MACNIVEN, TINA GOODISON AND DAVID RICHARDSON Department of Psychology, McMaster University, Hamilton, Ontario, L8S 4K1 Canada Received 13 January 1993 DECATANZARO, D., E. MACNIVEN, T. GOODISON AND D. RICHARDSON. Estrogen antibodies reduce vulnerability to stress-induced failure of intrauterine implantation in inseminated mice. PHYSIOL BEHAV 55(1) 35-38, 1994.--In Experiment 1, inseminated mice were randomly assigned to either an undisturbed control condition or four conditions involving exposure to restraint stress on days l through 5 of pregnancy. Restrained animals received one of three doses of estrogen antibodies or just vehicle injections on each day of restraint. Restrained animals receiving vehicle only showed significantly fewer uterine implantation sites than did unrestrained controls, while restrained animals given estrogen antibodies showed more implantation sites than did vehicle-treated restrained animals. In Experiment 2, varied dosages of refined estrogen antibodies were administered to inseminated females concurrent to restraint-stress on days 1 through 5 of pregnancy. More females receiving the higher dosages of antibodies produced litters than did restrained females with just vehicle injections, and at the highest dose the number of litters was similar to that produced by undisturbed control females. These results converge with other evidence to suggest that stress-induced pregnancy blocks are mediated by estrogens. Stress Pregnancy disruption Implantation Estrogen Estrogen antibodies Restraint A variety of psychological stressors have adverse effects upon early pregnancy in mammals (5). Pregnancy can be blocked by diverse stressors applied during the preimplantation period, in- cluding chronic restraint (8,1 l, 17), daily handling (l 4), over- crowding (2), forced swimming or loud noise (19), high ambient temperatures (16), exposure to strange males (1), and predator exposure (3,11). The hormonal mechanisms underlying such pregnancy blocks need further definition. Existing data suggest that hormones normally associated with stress, adrenal corticosteroids, and cat- echolamines, may not be as important in the mediation of this effect as are the primary gonadal hormones, progesterone, and estrogen (4,6, l 1). Indeed, relatively minute amounts of exoge- nous estrogens will reliably block pregnancy, whereas exogenous corticosterone is apparently without effect even at high dosages (6). A previous study examined the effects of chronic restraint stress on steroid levels in early pregnancy in rats, indicating that endogenous estradiol levels were enhanced in stressed animals as compared to controls (12). If pregnancy blocks are caused by excessive estrogen levels induced by stress, then the administration of an agent effective in decreasing estrogen activity might allow pregnancy to continue in the face of stress. Biological actions of a hormone can be neutralized or diminished through the introduction of a high- Requests for reprints should be addressed to Denys deCatanzaro. affinity antibody via passive immunization (15). The purpose of these experiments was to investigate whether a stress-induced pregnancy block could be counteracted through the administra- tion of an estrogen antibody. EXPERIMENT 1 This experiment was conducted using serum extracted from rabbits treated or not treated with estradiol, and uterine im- plantation sites were examined rather than allowing females to bear litters. Method Subjects were female HS (heterogeneous strain) mice bred in our laboratory from stock originally obtained from the De- partment of Zoology at the University of Toronto. After weaning and prior to insemination, females were housed in groups of four or five in standard polypropylene cages measuring 28 x 16 X 11 (height) cm with wire grid tops allowing continuous access to food and water. The colony room was maintained under a reversed 10:14 h dark:light cycle and at 21 _ I°C. HS males were housed individually under these same conditions. When the females were at least 65 days of age, they were each housed alone at the commencement of the dark phase of 35