Adverse effects of advanced glycation end products on embryonal development.
We studied the effects of advanced glycation end products (AGEs), which are known to accumulate in patients with diabetes, autoimmune diseases, or those who smoke, on embryonal development. Pronuclear (PN) embryos were obtained by flushing the fallopian tubes of rats after superovulation and mating. The cleavage rate and blastocyst yield were evaluated at 24, 72, 96, and 120 h of culture. Glyoxal, an AGE-forming aldehyde, suppressed embryonal development at every stage from PN to blastocyst in a concentration-dependent manner. The cleavage rate of the embryo was also signifi cantly decreased by treatment with glyoxal at concentrations of 1 mM or higher. The blastocyst yield was significantly decreased by treatment with glyoxal at concentrations of 0.5 mM or higher. N-acetyl-L-cysteine (L-NAC) at 1 mM significantly suppressed the glyoxal-induced embryonal toxicity. BSA-AGEs at 5 microg/ml or higher concentration signifi cantly reduced the cleavage rate and blastocyst yield compared to those for BSA-treated embryos. L-NAC at 1 mM significantly suppressed BSAAGE-induced embryonal toxicity. Because AGEs are embryo-toxic, AGE contamination may influence the pregnancy rate of in vitro fertilization and embryo transfer. AGEs, which are increased in women under pathological conditions, may also be involved in their infertility.
Hao
Lin
L
Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Noguchi
Soichi
S
Kamada
Yasuhiko
Y
Sasaki
Aiko
A
Matsuda
Miwa
M
Shimizu
Keiko
K
Hiramatsu
Yuji
Y
Nakatsuka
Mikiya
M
D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005865:Gestational Age; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology*; D006037:Glyoxal / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D017127:Glycation End Products, Advanced; D006037:Glyoxal