title: Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals.
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.
authors.affiliation: Cell Physiology Laboratory, Biochemistry Unit, Department of Zoology, Banaras Hindu University, Varanasi, 221005 India.
authors.forename: Shail K
authors.initials: SK
authors.lastname: Chaube
authors.affiliation: Department of Reproductive Biomedicine, National Institute of Health and Family Welfare, Baba Gang Nath Marg, Munirka, New Delhi, 110067 India.
authors.forename: Tulsidas G
authors.initials: TG
authors.lastname: Shrivastav
authors.affiliation: Cell Physiology Laboratory, Biochemistry Unit, Department of Zoology, Banaras Hindu University, Varanasi, 221005 India.
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Tiwari
authors.affiliation: Cell Physiology Laboratory, Biochemistry Unit, Department of Zoology, Banaras Hindu University, Varanasi, 221005 India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Cell Physiology Laboratory, Biochemistry Unit, Department of Zoology, Banaras Hindu University, Varanasi, 221005 India.
authors.forename: Anima
authors.initials: A
authors.lastname: Tripathi
authors.affiliation: Department of Kayachikitsa, Faculty of Ayurveda, Banaras Hindu University, Varanasi, 221005 India.
authors.forename: Ajai K
authors.initials: AK
authors.lastname: Pandey
keywords: Aqueous neem leaf extract; DNA fragmentation; Granulosa cell; Mitochondria-mediated oocyte apoptosis; Reactive oxygen species