Pentose phosphate pathway activity: effect on in vitro maturation and oxidative status of bovine oocytes

Abstract

26The relationship between the pentose phosphate pathway (PPP) activity in COCs and 27 oxidative and mitochondrial activity in bovine oocytes was evaluated, with the aim of 28 analyzing the impact of two inhibitors (NADPH, 6-AN) and a stimulator (NADP) of the 29 key enzymes of PPP on the maturation rate, the oxidative and mitochondrial activity, and 30 the mitochondrial distribution in oocytes. The percentage of COCs with PPP activity, 31(assessed using BCB staining), glucose uptake, lactate production, and meiotic maturation 32 rate diminished when 6-AN was added to the maturation media (p<0.05). The addition of 33 NADPH did not modify glucose uptake and lactate production, while the COC PPP activity 34 and the meiotic maturation rates decreased (p<0.05). The presence of NADP in the 35 maturation medium had no effect on COC PPP activity rate, glucose uptake, lactate 36 production and meiotic maturation rate. However, in the absence of gonadotrophin 37 supplementation NADP stimulated both glucose uptake and lactate production at the

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

“…Human studies support these findings by showing increased early follicular phase serum FSH levels in mothers of children with Down's syndrome compared with mothers with normal offspring (231). Whether the adverse effect of high FSH exposure on oocyte nuclear maturity is accompanied by diminished E 2 or inhibin-negative feedback from follicle depletion or is based upon perturbed FSH action on chromosome segregation, through either cellular checkpoints or glucose metabolism, remains unclear (65,230,232).…”

“…Within the COC, some glucose enters the pentose phosphate pathway (PPP) through glucose-6-phosphate dehydrogenase (G6PDH) to produce ribose-5-phosphate as a nucleotide precursor (65). In this way, the PPP also controls the oxidative status of the oocyte by producing nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for lipid, steroid, and nucleic acid synthesis (65).…”

“…In this way, the PPP also controls the oxidative status of the oocyte by producing nicotinamide adenine dinucleotide phosphate (NADPH) as a cofactor for lipid, steroid, and nucleic acid synthesis (65). Additional glucose enters the hexosamine biosynthesis pathway to provide substrate for hyaluronic acid production during extracellular matrix expansion and O-linked protein glycosylation for cell signaling and fuel sensing (61,66).…”

Intrafollicular cortisol levels inversely correlate with cumulus cell lipid content as a possible energy source during oocyte meiotic resumption in women undergoing ovarian stimulation for in vitro fertilization

“…Synthesized from cholesterol via pathways initiated by CYP7A1 or CYP27A1, bile acids can act through bile acid-activated receptors in various tissues to regulate lipid and glucose homeostasis in conjunction with the glucocorticoid receptor (50, 51). Whether similar events affect the relationship between FF cortisol and cumulus cell lipid is unknown, although redundant energy pathways within the periovulatory follicle during meiosis likely account for our finding of only a moderate inverse relationship between FF cortisol and cumulus cell lipid content (52, 53). …”

Nutrient pathways regulating the nuclear maturation of mammalian oocytes

“…Moreover, pharmacological modification of the PPP demonstrated that its activity was associated with meiotic resumption . A prominent role for this pathway in nuclear maturation is supported by additional studies in mice and other species Sakkas 1999, 2005;Herrick at al 2006;Alvarez et al 2013;Gutnisky et al 2014). Kim et al (2012) reported that the PPP is not involved in GVBD in mouse oocytes but, rather, progression beyond MI; however, they tested spontaneous maturation in DOs as opposed to meiotic induction in CEOs, as was the case in our studies.…”