TY - JOUR
T1 - Nitric oxide extends the oocyte temporal window for optimal fertilization
AU - Goud, Pravin T.
AU - Goud, Anuradha P.
AU - Diamond, Michael P.
AU - Gonik, Bernard
AU - Abu-Soud, Husam M.
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant RO1 HL066367 (to H.M.A.-S.), The American Society of Reproductive Medicine-Ortho Women's Health Grant (to P.T.G), and the Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA. The authors sincerely thank Riyaz-Ul-Haq, M.D., for his technical support with confocal microscopy, and Michael Kruger, M.A., Statistician, for his advice regarding statistical tests.
PY - 2008/8/15
Y1 - 2008/8/15
N2 - Deteriorating oocyte quality is a critical hurdle in the management of infertility, especially one associated with advancing age. In this study, we explore the role of nitric oxide (NO) on the sustenance of oocyte quality postovulation. Sibling oocytes from superovulated mice were subjected to intracytoplasmic sperm injection (ICSI) with cauda-epididymal spermatozoa following exposure to either the NO donor, S-nitroso-N-acetylpenicillamine (SNAP, 0.23 μM/min), an NO synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 1 mM), or an inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 100 μM); while their sibling oocytes were subjected to ICSI either before (young) or after culture for the corresponding period of time (old). Outcomes of normal fertilization, cleavage, and development to the morula and blastocyst stages were compared. Embryos from each subgroup were also subjected to TUNEL assay for apoptosis. A significant deterioration in the ability of the oocytes to undergo normal fertilization and development to morula and blastocyst stages occurred among oocytes aged in culture medium compared to their sibling cohorts subjected to ICSI immediately after ovulation (P < 0.05). This deterioration was prevented in oocytes exposed to SNAP. In contrast, exposure to L-NAME or ODQ resulted in a significant compromise in fertilization and development to the morula and blastocyst stages (P < 0.05). Finally, apoptosis was noted in embryos derived from aged oocytes and those exposed to L-NAME or ODQ, but not in embryos derived from young oocytes or oocytes exposed to SNAP. Thus, NO is essential for sustenance of oocyte quality postovulation.
AB - Deteriorating oocyte quality is a critical hurdle in the management of infertility, especially one associated with advancing age. In this study, we explore the role of nitric oxide (NO) on the sustenance of oocyte quality postovulation. Sibling oocytes from superovulated mice were subjected to intracytoplasmic sperm injection (ICSI) with cauda-epididymal spermatozoa following exposure to either the NO donor, S-nitroso-N-acetylpenicillamine (SNAP, 0.23 μM/min), an NO synthase (NOS) inhibitor, Nω-nitro-L-arginine methyl ester (L-NAME, 1 mM), or an inhibitor of soluble guanylyl cyclase (sGC), 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ, 100 μM); while their sibling oocytes were subjected to ICSI either before (young) or after culture for the corresponding period of time (old). Outcomes of normal fertilization, cleavage, and development to the morula and blastocyst stages were compared. Embryos from each subgroup were also subjected to TUNEL assay for apoptosis. A significant deterioration in the ability of the oocytes to undergo normal fertilization and development to morula and blastocyst stages occurred among oocytes aged in culture medium compared to their sibling cohorts subjected to ICSI immediately after ovulation (P < 0.05). This deterioration was prevented in oocytes exposed to SNAP. In contrast, exposure to L-NAME or ODQ resulted in a significant compromise in fertilization and development to the morula and blastocyst stages (P < 0.05). Finally, apoptosis was noted in embryos derived from aged oocytes and those exposed to L-NAME or ODQ, but not in embryos derived from young oocytes or oocytes exposed to SNAP. Thus, NO is essential for sustenance of oocyte quality postovulation.
KW - Apoptosis
KW - Fertilization
KW - Intracytoplasmic sperm injection (ICSI)
KW - Nitric oxide
KW - Oocyte postovulatory aging
KW - Oocyte quality
KW - Oocyte temporal window
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U2 - 10.1016/j.freeradbiomed.2008.04.035
DO - 10.1016/j.freeradbiomed.2008.04.035
M3 - Article
C2 - 18489913
AN - SCOPUS:46649113722
SN - 0891-5849
VL - 45
SP - 453
EP - 459
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 4
ER -