Oxidative phosphorylation and the tricarboxylic acid cycle are essential for normal development of mouse ovarian follicles

Wycherley, G.; Kane, M. T.; Hynes, A. C.

doi:10.1093/humrep/dei132

Cited by 24 publications

(10 citation statements)

References 25 publications

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“…The predominance of glycolytic energy production in large follicles is well documented (Boland et al 1993, Gull et al 1999, and the enzymatic machinery for oxidative glucose metabolism is already present at preantral stages, including human follicles (Roy & Terada 1999). It is unlikely that glycolysis is the sole source of energy in mouse follicles, because inhibition of aerobic metabolism seriously inhibits normal growth (Wycherley et al 2005). However, fully grown, but not growing, mouse oocytes promote the expression of glycolytic pathway components in cumulus cells (Sugiura et al 2005), a phenomenon that is consistent with our observations of glycolysis only accounting for a small fraction of glucose used by preantral follicles, which contain small oocytes.…”

Section: Discussionmentioning

confidence: 99%

“…It is likely that cultured follicles will also be susceptible to the culture environment, for example, glucose metabolism by cultured preovulatory mouse follicles exposed to glucose concentrations of 1-2 mM has glucose consumption rates approximately fourfold lower (Boland et al 1994b) than those observed in the current study, in which 5.5 mM glucose was used. Oxygen availability can also profoundly affect follicle metabolism (Wycherley et al 2005). All this highlights the requirement for further thorough investigation into factors influencing metabolism of cultured follicles and characterisation of the endocrine and nutritional milieu to which they are exposed naturally in vivo.…”

Section: Discussionmentioning

confidence: 99%

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Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro

Harris¹,

Adriaens²,

Leese³

et al. 2007

Reproduction

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Metabolic markers are potentially valuable for assessment of follicle development in vitro. Carbohydrate metabolism of murine preantral follicles grown to maturity over 13 days in vitro has been measured, and metabolism of resulting oocyte-cumulus complexes (OCCs) and denuded oocytes has been compared with in vivo ovulated control counterparts. Spent follicle culture media were analysed for glucose, lactate and pyruvate concentrations. During follicle in vitro growth, glycolysis accounted for a rise from w24 to 60% of all glucose consumed. Ovulation induction caused a significant increase in glucose uptake and lactate production by in vitrogrown follicles to 71.7G1.2 and 96.6G4.8 nmoles/day respectively. OCCs grown in vitro had significantly higher rates of glucose consumption and lactate and pyruvate production (110.1G3.5, 191.8G8.9 and 31.7G1.7 pmoles/h respectively) than in vivo ovulated controls (67.4G8.1, 113.9G17.1 and 20.2G4.0 pmoles/h respectively), but a reduced capacity for pyruvate consumption (1.13G0.06 vs 1.49G0.06 pmoles/h by in vivo ovulated oocytes). Metabolism of OCCs was affected by the quality of the original follicle. In vitro-grown oocytes had a reduced cytoplasmic volume when compared with controls (168.3G2.0 vs 199.0G3.2 proportionately respectively) but a similar rate of metabolism per unit volume. Meiotic status influenced metabolism of both OCCs and denuded oocytes. In conclusion, glucose consumption and lactate production by cultured follicles increased in tandem with developmental progression and were stimulated prior to ovulation. Additionally, the metabolic profiles of in vitro produced OCCs and the oocytes within them are affected by long-term exposure to the culture environment. Reproduction (2007) 134 415-424

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro

Harris¹,

Adriaens²,

Leese³

et al. 2007

Reproduction

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“…In the particular case of ovaries, the appearance of such Cd effects could explain, at least in part, why oocytes of Cd pre-contaminated eels could not reach final maturation and subsequently why these oocytes were subjected to atresia at the end of the experiment. Indeed, several studies carried out on fish, mammalian and amphibian oocytes have highlighted the vital role of oxidative phosphorylation during final maturation (Brachet et al 1975;Habibi and Lessman 1986;Wycherley et al 2005;Johnson et al 2007). For example, the use of inhibitors or uncouplers of oxidative phosphorylation was found to abolish germinal vesicle migration and breakdown in ovaries of female goldfish (Habibi and Lessman 1986).…”

Section: Discussionmentioning

confidence: 99%

Ovarian gene transcription and effect of cadmium pre-exposure during artificial sexual maturation of the European eel (Anguilla anguilla)

Pierron

Baudrimont

Dufour³

et al. 2009

Biometals

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European eels are dangerously threatened with extinction. Recent advances tend to show that pollution could, in addition to other already identified factors, contribute to this drama. In a previous report, cadmium (Cd) pre-exposure was found to strongly stimulate the pituitary-liver-gonad axis of maturing female silver eels, leading, lastly, to oocytes atresia and eels mortality. The present work was performed to get more insights into the effects of Cd preexposure on eels' ovaries. The transcription levels of various genes involved in mitochondrial metabolism, in the cellular response to metal (metallothioneins, MTs) and oxidative stress (catalase, CAT) were investigated. Our results show that ovarian growth is associated with an up-regulation of mitochondrial genes. However, Cd pre-exposure was found to significantly impair this up-regulation. Such findings could explain, at least in part, why oocytes of Cd pre-contaminated eels could not reach final maturation. Concerning MTs, despite the end of the experiment was marked by a strong increase in their gene transcription levels in both eel groups, MTs protein content was found to increase only in the case of Cd pre-contaminated eels. Since this increase in MTs protein content was associated with a massive entry of Cd in gonads, our findings suggest that MTs mRNA, that are normally accumulated in oocytes to cope with the future needs, can be activated and translated in response to Cd exposure.

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“…Studies in mice (40) and humans (37) where oxidative metabolism was inhibited have resulted in poor oocyte development and metabolism and low fertilization competence. In our cultures, elevated levels of lactate indicate that more pyruvate was being produced.…”

Section: E900mentioning

confidence: 99%

Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival

Makanji¹,

Tagler

Pahnke³

et al. 2014

American Journal of Physiology-Endocrinology and Metabolism

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Makanji Y, Tagler D, Pahnke J, Shea LD, Woodruff TK. Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival. Am J Physiol Endocrinol Metab 306: E893-E903, 2014. First published February 25, 2014 doi:10.1152/ajpendo.00484.2013.-Oxygen tension is critical for follicle growth and metabolism, especially for early-stage follicles, where vascularity is limited. Its role and underlying mechanism in the in vitro activation and maturation of immature to ovulatory follicles is largely unknown. In this study, early secondary (110 m) murine follicles were isolated and encapsulated in alginate hydrogels to replicate the in vivo environment of the growing/maturing follicle. Encapsulated follicles were cultured for 8 days at either 2.5 or 20% O2. Survival (2.6-fold) and growth (1.2-fold) were significantly higher for follicles cultured at 2.5% compared with 20% O2. Using a mouse hypoxia-signaling pathway qRT-PCR array and GeneGo Metacore analysis, we found that direct target genes of the hypoxia-activated HIF1-complex were significantly upregulated in follicles cultured for 8 days at 2.5% compared with 20% O2, including the carbohydrate transport and metabolism genes Slc2a3, Vegfa, Slc2a1, Edn1, Pgk1, Ldha, and Hmox1. Other upregulated genes included carbohydrate transporters (Slc2a1, Slc2a3, and Slc16a3) and enzymes essential for glycolysis (Pgk1, Hmox1, Hk2, Gpi1, Pfkl, Pfkp, Aldoa, Gapdh, Pgam1, Eno1, Pkm2, and Ldha). For follicles cultured at 2.5% O2, a 7.2-fold upregulation of Vegfa correlated to an 18-fold increase in VEGFA levels, and a 3.2-fold upregulation of Ldha correlated to a 4.8-fold increase in lactate levels. Both VEGFA and lactate levels were significantly higher in follicles cultured at 2.5% compared with 20% O2. Therefore, enhanced hypoxia-mediated glycolysis is essential for growth and survival of early secondary follicles and provides vital insights into improving in vitro culture conditions. hypoxia; ovarian; follicle metabolism; glycolysis; oxygen GROWTH AND MATURATION OF OVARIAN FOLLICLES requires coordinated activity of various growth factors and hormones that interact with the physical environment of the follicle, including pH, temperature, and oxygen (O 2 ) tension. O 2 is critical for aerobic ATP production, in which pyruvate is converted to energy; however, excess O 2 generates free radicals and reactive oxygen species, which can damage the oocyte and its precious DNA cargo within the follicle (44). By design, ovarian follicles operate in a moderate hypoxic environment rather than an anoxic one (16). Granulosa cells use relatively less O 2 and convert glucose to pyruvate and lactate via the glycolytic pathway; the pyruvate is shunted to oocyte, which uses it and O 2 to create ATP via the TCA cycle (8, 13).The ability to culture follicles in vitro to produce mature, fertilizable oocytes has potential clinical applications in fertility preservation, and yet recapitulating the complexity of follicle growth and metabolism in vitro has been chall...

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Oxidative phosphorylation and the tricarboxylic acid cycle are essential for normal development of mouse ovarian follicles

Abstract: Aerobic metabolism and an adequate oxygen supply are essential for normal follicular development.

Cited by 24 publications

References 25 publications

Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro

Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro

Ovarian gene transcription and effect of cadmium pre-exposure during artificial sexual maturation of the European eel (Anguilla anguilla)

Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival

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