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) induc...
Ausführliche Beschreibung
Autor*in: |
Chaube, Shail K [verfasserIn] Shrivastav, Tulsidas G [verfasserIn] Tiwari, Meenakshi [verfasserIn] Prasad, Shilpa [verfasserIn] Tripathi, Anima [verfasserIn] Pandey, Ajai K [verfasserIn] |
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E-Artikel |
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Sprache: |
Englisch |
Erschienen: |
2014 |
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Schlagwörter: |
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Übergeordnetes Werk: |
Enthalten in: SpringerPlus - London : Biomed Central, 2012, 3(2014), 1 vom: 26. Aug. |
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Übergeordnetes Werk: |
volume:3 ; year:2014 ; number:1 ; day:26 ; month:08 |
Links: |
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DOI / URN: |
10.1186/2193-1801-3-464 |
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Katalog-ID: |
SPR032756941 |
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520 | |a 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. | ||
650 | 4 | |a Aqueous neem leaf extract |7 (dpeaa)DE-He213 | |
650 | 4 | |a Reactive oxygen species |7 (dpeaa)DE-He213 | |
650 | 4 | |a Granulosa cell |7 (dpeaa)DE-He213 | |
650 | 4 | |a DNA fragmentation |7 (dpeaa)DE-He213 | |
650 | 4 | |a Mitochondria-mediated oocyte apoptosis |7 (dpeaa)DE-He213 | |
700 | 1 | |a Shrivastav, Tulsidas G |e verfasserin |4 aut | |
700 | 1 | |a Tiwari, Meenakshi |e verfasserin |4 aut | |
700 | 1 | |a Prasad, Shilpa |e verfasserin |4 aut | |
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700 | 1 | |a Pandey, Ajai K |e verfasserin |4 aut | |
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10.1186/2193-1801-3-464 doi (DE-627)SPR032756941 (SPR)2193-1801-3-464-e DE-627 ger DE-627 rakwb eng 600 ASE Chaube, Shail K verfasserin aut Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. Aqueous neem leaf extract (dpeaa)DE-He213 Reactive oxygen species (dpeaa)DE-He213 Granulosa cell (dpeaa)DE-He213 DNA fragmentation (dpeaa)DE-He213 Mitochondria-mediated oocyte apoptosis (dpeaa)DE-He213 Shrivastav, Tulsidas G verfasserin aut Tiwari, Meenakshi verfasserin aut Prasad, Shilpa verfasserin aut Tripathi, Anima verfasserin aut Pandey, Ajai K verfasserin aut Enthalten in SpringerPlus London : Biomed Central, 2012 3(2014), 1 vom: 26. Aug. (DE-627)718615298 (DE-600)2661116-8 2193-1801 nnns volume:3 year:2014 number:1 day:26 month:08 https://dx.doi.org/10.1186/2193-1801-3-464 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2014 1 26 08 |
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10.1186/2193-1801-3-464 doi (DE-627)SPR032756941 (SPR)2193-1801-3-464-e DE-627 ger DE-627 rakwb eng 600 ASE Chaube, Shail K verfasserin aut Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. Aqueous neem leaf extract (dpeaa)DE-He213 Reactive oxygen species (dpeaa)DE-He213 Granulosa cell (dpeaa)DE-He213 DNA fragmentation (dpeaa)DE-He213 Mitochondria-mediated oocyte apoptosis (dpeaa)DE-He213 Shrivastav, Tulsidas G verfasserin aut Tiwari, Meenakshi verfasserin aut Prasad, Shilpa verfasserin aut Tripathi, Anima verfasserin aut Pandey, Ajai K verfasserin aut Enthalten in SpringerPlus London : Biomed Central, 2012 3(2014), 1 vom: 26. Aug. (DE-627)718615298 (DE-600)2661116-8 2193-1801 nnns volume:3 year:2014 number:1 day:26 month:08 https://dx.doi.org/10.1186/2193-1801-3-464 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2014 1 26 08 |
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10.1186/2193-1801-3-464 doi (DE-627)SPR032756941 (SPR)2193-1801-3-464-e DE-627 ger DE-627 rakwb eng 600 ASE Chaube, Shail K verfasserin aut Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. Aqueous neem leaf extract (dpeaa)DE-He213 Reactive oxygen species (dpeaa)DE-He213 Granulosa cell (dpeaa)DE-He213 DNA fragmentation (dpeaa)DE-He213 Mitochondria-mediated oocyte apoptosis (dpeaa)DE-He213 Shrivastav, Tulsidas G verfasserin aut Tiwari, Meenakshi verfasserin aut Prasad, Shilpa verfasserin aut Tripathi, Anima verfasserin aut Pandey, Ajai K verfasserin aut Enthalten in SpringerPlus London : Biomed Central, 2012 3(2014), 1 vom: 26. Aug. (DE-627)718615298 (DE-600)2661116-8 2193-1801 nnns volume:3 year:2014 number:1 day:26 month:08 https://dx.doi.org/10.1186/2193-1801-3-464 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2014 1 26 08 |
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10.1186/2193-1801-3-464 doi (DE-627)SPR032756941 (SPR)2193-1801-3-464-e DE-627 ger DE-627 rakwb eng 600 ASE Chaube, Shail K verfasserin aut Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. Aqueous neem leaf extract (dpeaa)DE-He213 Reactive oxygen species (dpeaa)DE-He213 Granulosa cell (dpeaa)DE-He213 DNA fragmentation (dpeaa)DE-He213 Mitochondria-mediated oocyte apoptosis (dpeaa)DE-He213 Shrivastav, Tulsidas G verfasserin aut Tiwari, Meenakshi verfasserin aut Prasad, Shilpa verfasserin aut Tripathi, Anima verfasserin aut Pandey, Ajai K verfasserin aut Enthalten in SpringerPlus London : Biomed Central, 2012 3(2014), 1 vom: 26. Aug. (DE-627)718615298 (DE-600)2661116-8 2193-1801 nnns volume:3 year:2014 number:1 day:26 month:08 https://dx.doi.org/10.1186/2193-1801-3-464 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2014 1 26 08 |
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10.1186/2193-1801-3-464 doi (DE-627)SPR032756941 (SPR)2193-1801-3-464-e DE-627 ger DE-627 rakwb eng 600 ASE Chaube, Shail K verfasserin aut Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals 2014 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. Aqueous neem leaf extract (dpeaa)DE-He213 Reactive oxygen species (dpeaa)DE-He213 Granulosa cell (dpeaa)DE-He213 DNA fragmentation (dpeaa)DE-He213 Mitochondria-mediated oocyte apoptosis (dpeaa)DE-He213 Shrivastav, Tulsidas G verfasserin aut Tiwari, Meenakshi verfasserin aut Prasad, Shilpa verfasserin aut Tripathi, Anima verfasserin aut Pandey, Ajai K verfasserin aut Enthalten in SpringerPlus London : Biomed Central, 2012 3(2014), 1 vom: 26. Aug. (DE-627)718615298 (DE-600)2661116-8 2193-1801 nnns volume:3 year:2014 number:1 day:26 month:08 https://dx.doi.org/10.1186/2193-1801-3-464 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 3 2014 1 26 08 |
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Neem (Azadirachta indica L.) leaf extract deteriorates oocyte quality by inducing ROS-mediated apoptosis in mammals |
abstract |
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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. |
abstractGer |
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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. |
abstract_unstemmed |
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 ($ H_{2} %$ O_{2} $) inside the follicular fluid results in the transfer of $ H_{2} %$ O_{2} $ from follicular fluid to the oocyte. The increased level of $ H_{2} %$ O_{2} $ 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. |
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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. 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