Mitochondrial fatty acid transport enzyme deficiency—implications for in vitro fertilization

Hull, M. Louise; Németh, Dávid; Hague, William; Wilkinson, Chris; Liebelt, Jan; Lane, Michelle; Feil, D.

doi:10.1016/j.fertnstert.2009.01.104

Cited by 4 publications

(5 citation statements)

References 16 publications

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“…Ablation of Acox1, a gene involved in b-oxidation of very long-chain fatty acids, leads to sterility in female mice associated with smaller ovaries (Fan et al 1996); however, the physiological mechanism linking Acox1 function and female sterility is yet to be investigated. There is also an interesting case study of a female patient with a functional mutation in the CPTII gene, seeking fertility treatment (Hull et al 2009). The oocytes and embryos of this patient were predicted to have CPTII enzyme deficiency until activation of the embryonic genome at the 8-cell stage and as such the culture media were adjusted to include more glucose for the culture of intact COCs and increased levels of pyruvate for cleavage stage embryos (Hull et al 2009).…”

Section: Metabolism Of Fatty Acids For the Production Of Atpmentioning

confidence: 99%

“…There is also an interesting case study of a female patient with a functional mutation in the CPTII gene, seeking fertility treatment (Hull et al 2009). The oocytes and embryos of this patient were predicted to have CPTII enzyme deficiency until activation of the embryonic genome at the 8-cell stage and as such the culture media were adjusted to include more glucose for the culture of intact COCs and increased levels of pyruvate for cleavage stage embryos (Hull et al 2009). While two previous intrauterine insemination cycles had failed, ICSI using carbohydrate-supplemented media resulted in the birth of a singleton baby, suggesting that plasticity in embryo metabolism allows for increased glycolysis to support development when b-oxidation is compromised.…”

Section: Metabolism Of Fatty Acids For the Production Of Atpmentioning

confidence: 99%

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Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation

2014

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Metabolism and ATP levels within the oocyte and adjacent cumulus cells are associated with quality of oocyte and optimal development of a healthy embryo. Lipid metabolism provides a potent source of energy and its importance during oocyte maturation is being increasingly recognised. The triglyceride and fatty acid composition of ovarian follicular fluid has been characterised for many species and is influenced by nutritional status (i.e. dietary fat, fasting, obesity and season) as well as lactation in cows. Lipid in oocytes is a primarily triglyceride of specific fatty acids which differ by species, stored in distinct droplet organelles that re-localise during oocyte maturation. The presence of lipids, particularly saturated vs unsaturated fatty acids, in in vitro maturation systems affects oocyte lipid content as well as developmental competence. Triglycerides are metabolised by lipases that have been localised to cumulus cells as well as oocytes. Fatty acids generated by lipolysis are further metabolised by b-oxidation in mitochondria for the production of ATP. b-oxidation is induced in cumulus-oocyte complexes (COCs) by the LH surge, and pharmacological inhibition of b-oxidation impairs oocyte maturation and embryo development. Promoting b-oxidation with L-carnitine improves embryo development in many species. Thus, fatty acid metabolism in the mammalian COC is regulated by maternal physiological and in vitro environmental conditions; and is important for oocyte developmental competence.

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Section: Metabolism Of Fatty Acids For the Production Of Atpmentioning

confidence: 99%

Section: Metabolism Of Fatty Acids For the Production Of Atpmentioning

confidence: 99%

Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation

2014

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“…Indeed, there are case reports of patients with adult-onset CPT II deficiency who become pregnant and went on to deliver preterm or full-term newborns [42-45]. In order to identify IVF patients at risk of functional L-carnitine deficiency further studies are to be conducted to measure simultaneously carnitine compounds and markers of free fatty acid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization

Várnagy

Bene

Sulyok

et al. 2013

Reprod Biol Endocrinol

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BackgroundL-carnitine-mediated beta-oxidation of fatty acids has a well established role in energy supply of oocytes and embryos. Disturbed carnitine metabolism may impair the reproductive potential in IVF and can serve as a biomarker of pregnancy outcome.MethodsOur study was performed between March 24, 2011 and May 9, 2011. We performed 44 unselected IVF cycles, (aged 23–40 years (mean: 32.3+/−5.1 years) and had BMI of 17.3-34.7 (mean: 23.80+/−4.9). Samples were also obtained from 18 healthy women of similar age admitted for minor elective surgery to serve as control for plasma carnitine profile. Serum and follicular fluid (FF) free carnitine (FC) and 20 major acylcarnitines (ACs) were measured by ESI/MS/MS method.ResultsSerum FC and AC levels in IVF patients were comparable to those in healthy control women. In FF FC and short-chain AC concentrations were similar to those in maternal serum, however, the levels of medium-chain, and long-chain AC esters were markedly reduced (p<0.05). The serum to FF ratio of individual carnitine compounds increased progressively with increasing carbon chain length of AC esters (p<0.05). There was a marked reduction in total carnitine, FC and AC levels of serum and FF in patients with oocyte number of >9 and/or with embryo number of >6 as compared to the respective values of <9 and/or <6 (p<0.05).ConclusionsIn IVF patients with better reproductive potential the carnitine/AC pathway appears to be upregulated that may result in excess carintine consumption and relative depletion of carnitine pool. Consequently, IVF patients may benefit from carnitine supplementation.

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“…CPT1A inhibition leads to decreased beta-oxidation and low number of blastocyst formation following oocyte fertilization (9). CPT2 gene mutation was associated with infertility (23). Not much work has been done on SLC22A5 gene coding for OCTN2 regulation.Role of CACT in reproduction is also not much elaborated.…”

Section: Clinical Implications and Future Prospectsmentioning

confidence: 99%

Mitochondrial Fatty Acid Transport System and its Relevance to Ovarian Function

2018

J. Infertil. Reprod. Biol.

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Mitochondrial fatty acid oxidation is integral to folliculogenesis and oocyte maturation. Mitochondrial fatty acid transport system includes molecules such as 3-hydroxy-4-trimethylamino butyrate or carnitine, organic cation transporter novel 2 (OCTN2), carnitine palmitoyl transferase (CPT1), CPT2, and carnitine-acylcarnitine translocase (CACT). These are essential molecules that play an important role in the transport of activated long chain fatty acids from cytosol to the mitochondrial matrix where these subsequently undergo beta-oxidation. It has been well established that fatty acid metabolism is vital for follicles and oocyte growth. This review highlights the possible role of mitochondrial fatty transport acid system in ovarian function.

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Mitochondrial fatty acid transport enzyme deficiency—implications for in vitro fertilization

Cited by 4 publications

References 16 publications

Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation

Lipids and oocyte developmental competence: the role of fatty acids and β-oxidation

Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization

Mitochondrial Fatty Acid Transport System and its Relevance to Ovarian Function

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