From: A matter of new life and cell death: programmed cell death in the mammalian ovary
Pathway | Ovarian event | PCD type | Upstream regulators | Downstream effectors | Effect on ovarian cells | References |
---|---|---|---|---|---|---|
PI3K/AKT | PGC depletion | Apoptosis | KITLG | Upregulation of BCL-2, BCL-XL, MCL-1 Inactivation of BIM, BAX, BAD, and FOXO3 | Pro-survival | |
Follicular atresia | Apoptosis | FSH, IGF, EGF, bFGF | Upregulation of NFκB, cFLIPL, BCL-2, MDM2, and XIAP Inactivation of caspase-8, BIM, BAX, BAD, FOXO1, and FOXO3 | Pro-survival | [77, 141,142,143,144, 150, 157,158,159,160,161,162,163,164,165,166,167,168,169,170, 173,174,175,176,177] | |
Autophagy | FSH | Downregulation of MAP1LC3-II, BECN1, ATG7, and ATG12 | Pro-survival | |||
Luteolysis | Apoptosis | PGF2α | Inhibition of AKT Upregulation of BAX | Pro-apoptotic | [247] | |
PLC/PKC | Follicular atresia | Apoptosis | FSH | Stabilization of cFLIPS | Pro-survival | [143] |
Luteolysis | Apoptosis | PGF2α | Activation of NFAT | Pro-apoptotic | ||
Ca2+/AMPK | Luteolysis | Autophagy | PGF2α | Activation of BECN1 Upregulation of MAP1LC3-II | Pro-autophagic | [286] |
MEK/ERK | PGC depletion | Apoptosis | KITLG | Activation of RPS6KA1, MYC, STAT1/3 | Pro-survival | |
Follicular atresia | Apoptosis | FSH through β-arrestin | Activation of RPS6KA1, MYC, STAT1/3 | Pro-survival | ||
Luteolysis | Apoptosis | LH/hCG through β-arrestin | Activation of RPS6KA1, MYC | Pro-survival | ||
Autophagy | PGF2α | Upregulation of MAP1LC3-II | Pro-autophagic | [288] | ||
cAMP/PKA | Follicular atresia | Apoptosis | FSH | Phosphorylation of CREB, ERK1/2, AKT, GSK3B, β-catenin, FOXO1, p38 MAPK Downregulation of BIM | Pro-survival | |
Luteolysis | Apoptosis | LH/hCG | Progesterone synthesis stimulation Activation of CREB, GSK3B, and β-catenin Upregulation of LHCGR, BCL-2, MCL-1, survivin, STAR, and PGE2α Downregulation of BAX and CD95/Fas | Pro-survival | ||
PGE2α | Upregulation of LHCGR, BCL-2, STAR | Pro-survival | ||||
Autophagy | LH/hCG | Downregulation of MAP1LC3-II | Pro-survival | [286] | ||
Estrogen signaling | Luteolysis | Apoptosis | Progesterone | Downregulation of CD95/Fas Upregulation of BCL-2 | Pro-survival | |
HIF1α | Follicular atresia | Autophagy | Hypoxic stress, FSH | Upregulation of PINK1, Parkin, and BNIP3 | Pro-survival | |
Luteolysis | Autophagy | PGF2α | Upregulation of BNIP3 | Pro-autophagic | [287] | |
JAK/STAT | PGC depletion | Apoptosis | LIF | Upregulation of BCL-2, BCL-XL, MCL-1 | Pro-survival | |
Follicular atresia | Apoptosis | IFNγ | Upregulation of CD95/Fas | Pro-apoptotic | ||
Luteolysis | Apoptosis | PGF2α | Activation of STAT3 Upregulation of SOCS3 | Not defined/pro-apoptotic | [247] | |
IFNγ | Upregulation of CD95/Fas | Pro-apoptotic | ||||
CHK2/p53/p63 | PGC depletion | Apoptosis | Lack of growth factors, nutrient starvation, stress | Activation of p53/TAp63 Upregulation of NOXA, BBC3, and BAX | Pro-apoptotic | |
Death receptor/FADD/caspase-8 | PGC depletion | Apoptosis | TNFα | Activation of BAK, BAX, and caspase-3 | Pro-apoptotic | [87] |
TRAIL | Activation of BAK, BAX, and caspase-3 | Pro-apoptotic | [88] | |||
Follicular atresia | Apoptosis | FasL | Activation of BAK, BAX, and caspase-3 | Pro-apoptotic | ||
TNFα | Activation of BAK, BAX, and caspase-3 Downregulation of BCL-2 | Pro-apoptotic | ||||
TRAIL/DR4/5 receptors | Activation of BAK, BAX, and caspase-3 | Pro-apoptotic | ||||
Luteolysis | Apoptosis | FasL | Activation of BAK, BAX, and caspase-3 | Pro-apoptotic | ||
TNFα | Activation of BAK, BAX, and caspase-3 Upregulation of CD95/Fas | Pro-apoptotic | ||||
NFκB-RelA | Follicular atresia | Autophagy | FSH | Activation of JNK Upregulation of MAP1LC3-II | Pro-autophagic, pro-survival | [193] |
Luteolysis | Apoptosis | IFNγ | Upregulation of CD95/Fas | Pro-apoptotic | ||
TNFα | Upregulation of CD95/Fas | Pro-apoptotic | ||||
RIPK1/RIPK3 | Follicular atresia | Apoptosis | SIRT1 | Activation of caspase-3 | Pro-apoptotic | [210] |
Necroptosis | AChE-R-derived peptide | Activation of MLKL | Pro-necroptotic | |||
Luteolysis | Apoptosis | PGF2α | Activation of RIPK3 and caspase-8 | Pro-apoptotic | [292] | |
Necroptosis | AChE-R-derived peptide | Activation of MLKL | Pro-necroptotic | [207] | ||
Ceramide | Activation of MLKL | Pro-necroptotic | [289] | |||
Iron turnover | PGC depletion | Ferroptosis | Transferrin, PCBP2 | SLC7A11 | Not defined | |
NF2/YAP | Follicular atresia | Ferroptosis | BNC1 inactivation | Downregulation of GPX4 Upregulation of NOX1, COX2, TFRC and ACSL4 | Pro-ferroptotic | [212] |
xc− system | Follicular atresia | Ferroptosis | circRHBG-miR-515-5p | Cystine metabolism | Pro-ferroptotic | [214] |
Pathways are not determined up to date | PGC depletion | Apoptosis | Starvation at birth | Upregulation of BAX | Pro-apoptotic | [103] |
Autophagy | Starvation at birth | Upregulation of MAP1LC3-II and LAMP1 | Pro-autophagic, contradictory effects | |||
Follicular atresia | Apoptosis | Oxidative stress | Upregulation of BIM and caspase-3 Activation of caspase-3 | Pro-apoptotic | [195] | |
Autophagy | Oxidative stress | Activation of JNK Upregulation of BECN1, ATG5, ATG7, and MAP1LC3-II | Pro-autophagic, pro-ADCD | |||
Luteolysis | Apoptosis | PGF2α | Upregulation of FasL, CD95/Fas, BAX, IFNγ, and TNFα Activation of caspase-3 | Pro-apoptotic | ||
TNFα | Stimulation of PGF2α secretion | Pro-apoptotic | [246] | |||
Autophagy | PGF2α | Upregulation of MAP1LC3-II | Pro-autophagic, pro-survival | [248] |