Infertility and recurrent miscarriage with complex II deficiency-dependent mitochondrial oxidative stress in animal models

• 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.

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 SDHCV69E 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.