Handbook of Vitamin C Research

The Role of Vitamin C in Human Reproduction 283produce increasing concentrations of progesterone. Ascorbic acid stimulates the productionof progesterone by luteinizing granulose cells and consequently increased progesteroneconcentrations block the uptake of ascorbic acid [14].Ascorbic acid has also been implicated in the regulation of oxytocin secretion by theovaries, suggesting a role in birth and breastfeeding [15]. It has been reported that ascorbicacid concentrations in luteal cells, corpus luteum and granulose cell undergoes endocrinecontrol while the presence of active ascorbic acid transport mechanisms in ovariangranulose- luteal cells supports the major role of the vitamin in the menstrual cycle [16, 17].Increased ascorbic acid concentration in follicular fluid compared to serum ascorbate‘slevel during the ovulation and / or post- ovulation steroidogenesis, is suggestive for itsimportant role in ovarian cycle [14, 18]. As the female reproductive system secrets estrogensand progesterone, to help develop corpus luteum ascorbic acid is perceived in all stages ofluteal development with the highest amounts present in the midluteal phase while collagen asa main component of the luteal extracellular matrix shows the highest concentration in themature tissue [19]. Ovulation and luteolysis are characterized by leukocytic infiltrationknown to generate superoxide in quantities sufficient to cause cell injury and death.Protection against Reactive Oxygen Species (ROS) is provided by ovarian antioxidants, mostnotably ascorbic acid and other vital agents, like vitamin E and glutathione [20-22]. Ascorbicacid inhibits apoptosis in granulosa cells, implying that this oxidant is important in theprevention of atresia and apoptosis [8, 17, 23].3. Ascorbic Acid and Oxidative Stressin Female ReproductionIn oocytes and embryos, various metabolic pathways and enzymes are known to produceendogenous ROS. ROS are produced continuously in mitochondria, due to the ―leakage‖ ofhigh energy electrons along the electron transport chain [24, 25]. Extensive researchdemonstrated that the production of ROS in early mouse embryos cultured in vitro is possiblydue to the xanthine oxidase system [26] or other enzymatic systems and exogenous factorssuch as amine oxidase. Amine oxidases, a family of enzymes including monoamine anddiamine oxidases (histaminases), tissue polyamine oxidases and serum oxidases are involvedin the production of hydrogen peroxide and aldehydes. Hydrogen peroxide is involved inapoptosis and destroys cancer cells implanted into areas where cell death occurs. In mouseembryos progressive deterioration and and death is correlates to hydrogen peroxide and/oraldehydes production by serum amine oxidase during oxidation of endogenous amines [27].Oxygen consumption, metallic cations, visible light and spermatozoa are also implicated inthe production of ROS [27-30] especially in the case of assisted reproductive technologiesand in vitro fertilization. [31]. Porcine embryos cultured under low (5%) and high (20%)oxygen concentrations, showed differences in developmental outcome to the blastocyst stage,in the accumulation of hydrogen superoxide (H 2 O 2 ) as well as in DNA fragmentation. Lowoxygen concentrations, decrease hydrogen superoxide content, leading to reduced DNAfragmentation and improved developmental potential [32].