Enhancing oxygen delivery to ovarian follicles by three different methods markedly improves growth in serum-containing culture medium
J. M. Connolly
A B C , M. T. Kane A , L. R. Quinlan A and A. C. Hynes A
+ Author Affiliations
- Author Affiliations
A Physiology, National University of Ireland Galway, University Road, Galway, Ireland.
B Department of Physiology and Biochemistry, Ross University School of Medicine, Knoxville Campus, 9731 Cogdill Road, Knoxville, TN 37932, USA.
C Corresponding author. Email: jenniferconnolly@rossu.edu
Reproduction, Fertility and Development 31(8) 1339-1352 https://doi.org/10.1071/RD18286
Submitted: 23 July 2018 Accepted: 7 February 2019 Published: 12 April 2019
Abstract
In vitro ovarian follicle culture systems are routinely used to study folliculogenesis and may provide solutions for infertility. Mouse follicles are typically cultured in standard gas-impermeable culture plates under gas phase oxygen concentrations of 5% or 20% (v/v). There is evidence that these conditions may not provide adequate oxygenation for follicles cultured as non-attached intact units in medium supplemented with serum and high levels of FSH. Three different methods of enhancing follicle oxygenation were investigated in this study: increasing the gas phase oxygen concentration, inverting the culture plates and using gas-permeable culture plates. Follicles cultured under 40% O2 were significantly larger (P < 0.01), had increased ovulation rates (P < 0.0001) and produced more oestradiol (P < 0.05) than follicles cultured under 20% O2. These effects were associated with reduced secretion of vascular endothelial growth factor (P < 0.05) and lactate (P < 0.05), and reduced expression of hypoxia-related genes. Increasing oxygen delivery with gas-permeable plates or by culture plate inversion also improved follicle growth (P < 0.01). An important aspect of enhancing oxygen delivery in this culture system is that it allows development of three-dimensional spherical mouse follicles over 6 days in serum- and FSH-supplemented medium to sizes comparable to in vivo-matured follicles (~500 μm in diameter). Such follicular development is not possible under hypoxic conditions.
Additional keywords: FSH, gas-permeable, gonadotoxic, hypoxia, infertility, oestrogen, VEGF.
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