Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo development in vitro.
Two-cell mouse embryos (B6D2F1) were cultured in the presence or absence of 100 microg/ml monoclonal antibodies specific for the mammalian 60 kDa (HSP60), 70 kDa (HSP70) and 90 kDa (HSP90) heat shock proteins. Embryo development was evaluated after 3, 5 and 7 days in culture by determining the number of blastocysts, hatched blastocysts and outgrown trophoblasts at the successive time points. At day 3, only 29% (22/75) of the embryos cultured with anti-HSP60 antibody developed to the blastocyst stage (P < 0.0001) as compared to 67% (31/46) of the embryos cultured with anti-HSP70, 72% (43/60) cultured with anti-HSP90, and 79% (49/62) in medium plus mouse IgG1. By day 5, hatched embryos were present in 28% (13/ 46) of the cultures containing anti-HSP70 (P < 0.0001), as opposed to 57% (34/60) containing anti-HSP90 and 73% (45/62) containing IgG1. At day 7, outgrown trophoblasts were observed in 9% (4/46) of cultures containing anti-HSP70 (P < 0.0001), 45% (27/60) containing anti-HSP90 (P < 0.01) and 66% (41/62) cultured in medium plus IgG1. Antibodies to different heat shock proteins exerted a detrimental effect on mouse embryo development at unique development stages. Immune sensitization to heat shock proteins may be a cause of reproductive failure.
Neuer
A
A
Department of Obstetrics and Gynecology, Cornell University Medical College, New York, NY 10021, USA.
Mele
C
C
Liu
H C
HC
Rosenwaks
Z
Z
Witkin
S S
SS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology*; D018834:Chaperonin 60 / Q000276:immunology; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000502:physiology; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000276:immunology; D018841:HSP90 Heat-Shock Proteins / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology*; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D013997:Time Factors
D000911:Antibodies, Monoclonal; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D007074:Immunoglobulin G