Abstract
Neem (Azadirachta indica L.) leaf has been widely used in ayurvedic system of medicine for fertility regulation for a long time. The molecular mechanism by which neem leaf regulates female fertility remains poorly understood. Animal studies suggest that aqueous neem leaf extract (NLE) induces reactive oxygen species (ROS) - mediated granulosa cell apoptosis. Granulosa cell apoptosis deprives oocytes from nutrients, survival factors and cell cycle proteins required for the achievement of meiotic competency of follicular oocytes prior to ovulation. Under this situation, follicular oocyte becomes more susceptible towards apoptosis after ovulation. The increased level of hydrogen peroxide (H2O2) inside the follicular fluid results in the transfer of H2O2 from follicular fluid to the oocyte. The increased level of H2O2 induces p53 activation and over expression of Bax protein that modulates mitochondrial membrane potential and trigger cytochrome c release. The increased cytosolic cytochrome c level induces caspase-9 and caspase-3 activities that trigger destruction of structural and specific proteins leading to DNA fragmentation and thereby oocyte apoptosis. Based on these animal studies, we propose that NLE induces generation of ROS and mitochondria-mediated apoptosis both in granulosa cells as well as in follicular oocyte. The induction of apoptosis deteriorates oocyte quality and thereby limits reproductive outcome in mammals.
Highlights
Neem plant (Azadirachta indica L.) has been considered as one of the most important medicinal plants worldwide
The Neem leaf extract (NLE) induces cytoplasmic granulation and deteriorates oocyte quality suggesting its potential use for female fertility regulation in brown dog ticks (Denardi et al 2010)
NLE triggers reactive oxygen species (ROS)-mediated granulosa cell and oocyte apoptosis The mechanism by which NLE has a direct access at the level of mammalian ovary and oocyte remains unclear
Summary
Neem plant (Azadirachta indica L.) has been considered as one of the most important medicinal plants worldwide. The NLE induces cytoplasmic granulation and deteriorates oocyte quality suggesting its potential use for female fertility regulation in brown dog ticks (Denardi et al 2010). The anti-fertility properties of neem extracts have been reported in several mammalian species (Mukherjee et al 1999; Subapriya and Nagini 2005).
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