Amino acid transport system L activity in developing mouse ovarian follicles.

Hum Reprod

Cancer Drug Discovery, Prince Henry's Institute, Monash Medical Centre, Clayton, Melbourne 3168, Australia.

Published: November 2011

AI Article Synopsis

  • The study investigates how the ovarian follicles in mice absorb L-leucine, an important amino acid, during their development, particularly in the presence of insulin-like growth factor (IGF)-1.
  • It was found that IGF-1 not only promotes follicle growth and survival but also influences the rate of L-leucine uptake, which varies at different maturity stages of the follicles.
  • The research highlights the role of specific transport mechanisms for amino acids and suggests that understanding these metabolic processes can enhance fertility treatments and in vitro maturation techniques.

Article Abstract

Background: Little is known about metabolic processes in the developing ovarian follicle. Using mouse ovarian follicles, we investigated uptake of L-leucine by follicles at varying stages of maturity in the presence of insulin-like growth factor (IGF)-1. METHODS Mouse ovarian follicles were cultured in vitro for 5 days in increasing concentrations of IGF-1, and follicle diameter and atresia measured as endpoints for growth. Uptake of (3)H-leucine was measured in follicles at different stages of development. In optimal IGF-1-mediated growth conditions, competitive inhibition of (3)H-leucine uptake by 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH), a non-metabolizable substrate analogue of L-leucine, was performed to demonstrate specificity of influx, via system L transporters. To test whether uptake rates were dependent on intracellular amino acid availability, follicles from in vitro cultures were pre-treated with L-phenylalanine prior to (3)H-leucine uptake.

Results: Follicle development (P< 0.001) and survival (P< 0.001) increased with IGF-1 treatment. As pre-antral follicles progressed to late antral stage, we observed an increase in L-leucine uptake, which was reduced in pre-ovulatory follicles. BCH decreased L-leucine uptake rates in early antral (P< 0.05), antral (P< 0.001) and pre-ovulatory follicles (P< 0.01). L-leucine influx increased in follicles preloaded with phenylalanine (trans-stimulation). In follicles lacking free intracellular amino acids (zero-trans suppression), uptake rate was reduced (P< 0.05).

Conclusions: These results demonstrate, for the first time, evidence of specific system L amino acid transport in intact, mouse ovarian follicles and profile L-leucine uptake during folliculogenesis. A better understanding of ovarian follicle metabolic pathways is necessary for improved in vitro maturation as well as determining the impact of altered metabolism on fertility.

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http://dx.doi.org/10.1093/humrep/der298DOI Listing

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