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$40 EFFECTS OF IMMUNIZATION WITH THE ~-SUBUNIT OF OVINE LUTEINIZIN~ HORMONE (oLH~) ON LUTEAL FUNCTION IN RHESUS MONKEYS. R.B.Thau, Y.Yamamoto, K.Sundaram and L.S.Seidman, Population Council, 1230 York Avenue, New York, N.Y. 10021. Active immunization with oLH~ reduced fertility in rhesus monkeys significantly but did not interfere with ovulation and regular menstrual cycles. However, progesterone production by the corpus luteum was significantly reduced and luteal phases were shorter. Corpus luteum rescue (chorionic gonadotropin in- duced prolongation of progesterone production by the corpus lu- teum beyond that of the infertile cycle) was not observed. We wished to determine if the absence of corpus luteum rescue was due to the neutralization of rhesus chorionic gonadotropin (rhCG) by the circulating oLH~ antibodies or to insufficient response of the corpus luteum to gonadotropic stimulus. We therefore treated 7 non-immunized controls and 8 immunized mon- keys for 5 days with increasing doses of hCG, beginning on day 17 of the cycle, hCG treatment stimulated progesterone product- ion in both groups and increased luteal phase length in the im- munized group, suggesting that the corpus luteum of monkeys im- munized with oLH~ exhibits a normal response to gonadotropic stimulus. Estradiol and 17~-hydroxyprogesterone concentrations were similar for both experimental groups. Unexpectedly, we found that peripheral concentrations of FSH during the follicu- lar phase were significantly elevated in immunized monkeys. These findings suggest that the shortened luteal phases may be associated with the increase in FSH concentrations and conse- quent impaired folliculogenesis during the follicular phase. AN ACTIVITY DERIVED FROM RABBIT SERUM CAUSING INTERRUPTION OF PREGNANCY IN NORMAL MICE. Cory Waters and Bha$irath Sinsh. t Department of Immunology and MRC Group on Immunoregulation, University of Alberta, Edmonton, Alberta, Canada T6G 2H7 Rabbit y-globulins (Cohn Fraction II) contains an activity which, if administered to mice in utero via the maternal cir- culation, causes either complete fetal resorption in virtually 100% of cases when given during the second trimester, or abor- tion of the litter, when given later in the pregnancy. Treated females whose pregnancies were thus interrupted can be successfully re-mated. All mouse strains tested are sensi- tive to the activity, although at different dosages and kinet- ics. Unlike many putatively contraceptive vaccines raised xenogeneically against rodent placentae, this activity does not cross-react with mouse kidney or result in any maternal pathology; it can be absorbed from the preparation with mouse placentae and testes, although not with erythrocytes, lympho-

An activity derived from rabbit serum causing interruption of pregnancy in normal mice

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Page 1: An activity derived from rabbit serum causing interruption of pregnancy in normal mice

$40

EFFECTS OF IMMUNIZATION WITH THE ~-SUBUNIT OF OVINE LUTEINIZIN~ HORMONE (oLH~) ON LUTEAL FUNCTION IN RHESUS MONKEYS. R.B.Thau, Y.Yamamoto, K.Sundaram and L.S.Seidman, Population Council, 1230 York Avenue, New York, N.Y. 10021.

Active immunization with oLH~ reduced fertility in rhesus monkeys significantly but did not interfere with ovulation and regular menstrual cycles. However, progesterone production by the corpus luteum was significantly reduced and luteal phases were shorter. Corpus luteum rescue (chorionic gonadotropin in- duced prolongation of progesterone production by the corpus lu- teum beyond that of the infertile cycle) was not observed. We wished to determine if the absence of corpus luteum rescue was due to the neutralization of rhesus chorionic gonadotropin (rhCG) by the circulating oLH~ antibodies or to insufficient response of the corpus luteum to gonadotropic stimulus. We therefore treated 7 non-immunized controls and 8 immunized mon- keys for 5 days with increasing doses of hCG, beginning on day 17 of the cycle, hCG treatment stimulated progesterone product- ion in both groups and increased luteal phase length in the im- munized group, suggesting that the corpus luteum of monkeys im- munized with oLH~ exhibits a normal response to gonadotropic stimulus. Estradiol and 17~-hydroxyprogesterone concentrations were similar for both experimental groups. Unexpectedly, we found that peripheral concentrations of FSH during the follicu- lar phase were significantly elevated in immunized monkeys. These findings suggest that the shortened luteal phases may be associated with the increase in FSH concentrations and conse- quent impaired folliculogenesis during the follicular phase.

AN ACTIVITY DERIVED FROM RABBIT SERUM CAUSING INTERRUPTION OF PREGNANCY IN NORMAL MICE. Cory Waters and Bha$irath Sinsh. t Department of Immunology and MRC Group on Immunoregulation, University of Alberta, Edmonton, Alberta, Canada T6G 2H7

Rabbit y-globulins (Cohn Fraction II) contains an activity which, if administered to mice in utero via the maternal cir- culation, causes either complete fetal resorption in virtually 100% of cases when given during the second trimester, or abor- tion of the litter, when given later in the pregnancy. Treated females whose pregnancies were thus interrupted can be successfully re-mated. All mouse strains tested are sensi- tive to the activity, although at different dosages and kinet- ics. Unlike many putatively contraceptive vaccines raised xenogeneically against rodent placentae, this activity does not cross-react with mouse kidney or result in any maternal pathology; it can be absorbed from the preparation with mouse placentae and testes, although not with erythrocytes, lympho-

Page 2: An activity derived from rabbit serum causing interruption of pregnancy in normal mice

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cytes, or kidney. The kinetics of the reaction are very rapid: within 1 hour of administration, histological changes occur in the basal decidua, leading to placental venous conges- tion and fetal death. The activity is sensitive to pre- treatment of the pregnant mouse with low doses of heparin, but not to atropine sulfate, cortisone, cimetidine, diphenhydra- mine and warfarin. The activity is labile to heating at 56 ° for 30 min, but is not present in commercial sources of rabbit complement.

tSupported by the Medical Research Council of Canada

PREGNANCY INTERRUPTION IN MICE WITH A SINGLE INTRAVENOUS INJECTION OF AN ACTIVITY DERIVED FROM RABBIT SERUM:

MORPHOLOGIC ASPECTS. Louis Honor~ and Cory Waters , Departments of Pathology and Immunology and MRC Group on Immunoregulationt, University of Alberta, Edmonton, Alberta, Canada, T6G 2H7

Single injections of rabbit y-globulins (Cohn Fraction II) given to BALB/cCr mice on day 14 of pregnancy consistently caused death and resorption of their entire litters without detectable maternal effects. By 40 mins post-injection (p.i.) the implantation sites were deeply engorged and histo- logically marked vascular congestion was seen in the fetal placenta, maternal decidua and metrial gland. At 6 hrs p°i. necrosis was also seen in the fetal tissues and decidua but not in the metrial gland. By 50 hrs p.i. the conceptuses had sloughed off and the implantation sites were undergoing repair while the retained metrial gland showed early de- generation. The mechanism underlying this effect is thought to be myometrial spasm with severe obstruction to venous outflow, interruption of the deciduo-placental circulation and fetal death.

tSupported by the Medical Research Council of Canada

PURIFICATION OF LOW MOLECULAR WEIGHT HUMAN SPERMATOZOAL ANTIGENIC COMPONENTS. Mettler, L., Tinneberg, G. and ~.

Czuppon. Department of Obstetrics and Gynecology, University of Kiel, FRG.

Low molecular weight human spermatozoal haptens were determin- ed in their antigenicity by immunoabsorbent test methods as well as by a new radioimmunoassay using 125-I-Protein-A as Tracer. After coupling these spermatozoal components to human