Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models. (April 2016)

• Record Type: Journal Article
• Authors: Ishii, Takamasa; Yasuda, Kayo; Miyazawa, Masaki; Mitsushita, Junji; Johnson, Thomas E.; Hartman, Phil S.; Ishii, Naoaki
• Is Part Of: Mechanisms of ageing and development. Volume 155(2016)
• Page Start: 22
• Page End: 35
• Publication Date: 2016-04
• Subjects: ROS reactive oxygen species -- TCA tricarboxylic acid -- SDH succinate dehydrogease -- OXPHOS mitochondrial oxidative phosphorylation -- ETC electron transport chain -- ANT adenine nucleotide transporter -- SDHC succinate dehydrogenase C subunit -- ETF electron transferring flavoprotein -- CoQ ubiquinone -- CAD caspase activated DNase -- ICAD inhibitor of caspase activated DNase -- TNF tumor necrosis factor -- TNFR1 TNF receptor 1 -- TRAIL TNF-related apoptosis-inducible ligand -- DISC death-inducing signaling complex -- AIF apoptosis-inducing factor -- TRADD TNFR1-associated death domain -- Apaf-1 apoptotic protease-activating factor-1 -- MPTP mitochondrial permeability transition pore -- cypD cyclophilin D -- VDAC voltage-dependent anion channel -- JNK c-Jun-N-terminal kinase -- ASK1 apoptosis signal-regulating kinase 1 -- 8-OHdG 8-hydroxydeoxyguanosine -- TUNEL terminal deoxynucleotidyl transferase dUTP nick end labeling -- NGF non-growing follicles -- HIF hypoxia inducible factors -- VEGF vascular endothelial growth factors -- VEGFR-1 VEGF receptor-1 -- PLGF placenta growth factor -- SOD superoxide dismutase -- Dox doxycycline -- HE hematoxilin-eosin -- ICM inner cell mass -- TE trophectoderm -- PKC protein kinase C -- DAG diacylglycerol -- PGE2 Prostaglandin E -- AA arachidonic acid -- PGF2 prostagladin F2 -- PGLs paragangliomas -- PHEOs phaeochromocytomas; Mitochondria -- Oxidative stress -- SDHC -- Infertility -- Miscarriage -- Embryopathy; Aging -- Periodicals; Developmental biology -- Periodicals; Aging -- Periodicals; Developmental Biology -- Periodicals; Vieillissement -- Périodiques; Biologie du développement -- Périodiques; Aging; Developmental biology; Periodicals; 612.67
• DOI: 10.1016/j.mad.2016.02.013
• Languages: English
• ISSNs: 0047-6374

Abstract

Highlights: SDHC mutation causes complex II deficiency-dependent oxidative stress in female reproductive organs, not male. The oxidative stress causes ovarian hemangiomas leading to abnormal follicle maturation. The oxidative stress does not affect spermatogenesis and early embryogenesis. The oxidative stress causes placental angiodysplasia and inflammation. The oxidative stress causes embryopathy and developmental arrest with excessive apoptosis. Abstract: Oxidative stress is associated with some forms of both male and female infertility. However, there is insufficient knowledge of the influence of oxidative stress on the maintenance of a viable pregnancy, including pregnancy complications and fetal development. There are a number of animal models for understanding age-dependent decrease of reproductive ability and diabetic embryopathy, especially abnormal spermatogenesis, oogenesis and embryogenesis with mitochondrial dysfunctions. Several important processes occur in mitochondria, including ATP synthesis, calcium ion storage, induction of apoptosis and production of reactive oxygen species (ROS). These events have different effects on the several aspects of reproductive function. Tet-mev-1 conditional transgenic mice, developed after studies with the mev-1 mutant of the nematode C. elegans, offer the ability to carefully regulate expression of doxycycline-induced mutated SDHC V69E levels and hence modulate endogenous oxidative stress. The mev-1 models have served to illuminate the effects of complex II deficiency-dependent mitochondrial ROS production, although interestingly they maintain normal mitochondrial and intracellular ATP levels. In this review, the reproductive dysfunctions are presented focusing on fertility potentials in each gamete, early embryogenesis, maternal conditions with placental function and neonatal development.