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. 2021 Jan 22;18(3):980. doi: 10.3390/ijerph18030980

Table 2.

NO and folliculogenesis.

Authors Animal Model NO Donors Used NOS Inhibitors Used Effects
Van Voorhish et al., 1995 [21] Rat In vivo -Highest levels of iNOS mRNA in unstimulated ovaries.
-After gonadotropin injection, iNOS mRNA declined to undetectable levels in ovaries containing ovulatory follicles before increasing slightly in ovaries containing copora lutea.
-iNOS expressed in granulosa cells of secondary follicles and small antral follicles.
-eNOS mRNA levels increased after gonadotropin stimulation and peaked in ovaries containing ovulatory follicles before declining in the luteal phase.
Jablonka-Shariff et al., 1997 [22] Rat In vivo -In immature ovaries and during follicular development, iNOS was expressed in the theca cell layer and stroma.
-After ovulation, iNOS was present only in the external layers of the developing corpus luteum.
Basini et al., 1998 [23] Bovine In vitro culture of granulosa cells collected from follicles divided according to their size, small (<5 mm) and large (>8 mm). -SNAP: 10−3 M, 10−4 M, 10−5M -Significant inhibition of DNA fragmentation in all the cells with the highest concentration of SNAP.
-Stimulation of cellular apoptosis in granulosa cells from large follicles with the lowest concentration of SNAP.
Matsumi et al., 1998 [24] Rat In vitro culture of granulosa cells -SNAP: 0.05 mM, 0.5 mM -Inverse correlation between iNOS expression and apoptotic changes in rat granulosa cells.
-The NO donor directly inhibited spontaneously occurring apoptosis.
Chen et al., 2005 [25] Rat In vitro culture of granulosa cells -SNAP: 0.05 mM, 0.2 mM, 0.5 mM -The induction of apoptosis in granulosa cells by 100 ng/ml rFasL in the presence of interferon-gamma was blocked by the concomitant addition of SNAP in a dose-dependent manner.
-rFasL significantly up-regulated caspase-3, -8, and -9 activities in granulosa cells, which were attenuated by concurrent treatment with SNAP (0.5 mM).
Dineva et al., 2008 [26] Human In vitro human granulosa/luteinized cells -SNP: 0.5 mM -AG: 0.5 mM -SNP treatment significantly lowered the caspase-3 activity that significantly increased after AG treatment.
Matsumi et al., 2000 [28] Rat In vitro culture of granulosa cells -SNAP: 0.05 mM, 0.2 mM, 0.5 mM -The in vitro induction of granulosa cell apoptosis by 10−6 M buserelin was inhibited by the addition of SNAP (0.5 mM)
-The percentage of apoptotic cells increased by the addition of 10−6 M buserelin but this increase was reverted by supplementation of SNAP (0.5 mM)
-Dose-dependent inhibition of DNA synthesis mediated by SNAP. At 0.5 mM, SNAP caused a 90% inhibition in DNA synthesis.

AG—Aminoguanidine bicarbonate; NO—Nitric oxide; NOS—Nitric oxide synthase; iNOS—inducible nitric oxide synthase; eNOS—endothelial nitric oxide synthase; rFasL—ecombinant Fas ligand; SNAP—S-nitroso-N-acetyl-penicillamine; SNP—Sodium nitroprusside; mRNA—Messenger RNA; DNA—deoxyribonucleic acid.