Monoclonal Antibodies Specific for Rat Relaxin: Production, Characterization and Use to Neutralize the Biological Actions of Endogenous Relaxin Throughout the Second Half of Pregnancy in the Rat
Lao Guico, Marilyn Serna
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https://hdl.handle.net/2142/71458
Description
Title
Monoclonal Antibodies Specific for Rat Relaxin: Production, Characterization and Use to Neutralize the Biological Actions of Endogenous Relaxin Throughout the Second Half of Pregnancy in the Rat
Author(s)
Lao Guico, Marilyn Serna
Issue Date
1988
Doctoral Committee Chair(s)
Sherwood, O. David
Department of Study
Physiology and Biophysics
Discipline
Physiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Animal Physiology
Abstract
The role of relaxin during pregnancy and at parturition in the rat is not absolutely established. There are limitations to the experimental approach used in the few studies that examined the influence of relaxin in the pregnant rat. These studies were unphysiological since they involved exogenous administration of porcine relaxin, progesterone and estrogen to ovariectomized pregnant rats. The purpose of the present research was to use a rigorous and physiological approach to determine the role of relaxin on birth in the rat. That approach involved the passive neutralization of endogenous relaxin bioactivity with monoclonal antibodies in intact pregnant rats.
To that end, several monoclonal antibodies specific for rat relaxin (MCA-rR) were developed. One MCA-rR, designated MCA1 (IgG1 kappa), which binds rat relaxin with high specificity and high affinity and also neutralizes rat relaxin's bioactivity in vivo, was selected for use in subsequent studies aimed at the passive neutralization of endogenous relaxin bioactivity in intact pregnant rats.
MCA1 was administered to intact rats from day 12 through day 22 of pregnancy. Animals were observed for birth continuously from 2100h on day 22 until 1200h on day 24. MCA1-treated rats exhibited prolonged duration of straining and litter delivery as well as reduced incidence of live pups compared with controls. Approximately 20-25% of fetuses and placentae were retained in utero at 1200h on day 24 in MCA1-treated rats; whereas, neither fetuses nor placentae were retained in control rats. Passive immunization with MCA1 throughout the second half of pregnancy had no apparent influence on normal ovarian function. The time of occurrence of the antepartum decline in serum progesterone levels as well as the time interval between the attainment of basal progesterone levels and the onset of litter delivery in MCA1-treated and control rats that delivered on day 23 were in close agreement with previous reports.
In conclusion, the prolonged duration of straining and litter delivery, reduced incidence of live pups, and increased incidence of retained fetuses and placentae following passive immunization with MCA1 established the physiological need for endogenous relaxin to attain normal delivery of the young in the rat.
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