Enhancing oxygen delivery to ovarian follicles by three different methods markedly improves growth in serum-containing culture medium
J. M. Connolly![https://orcid.org/0000-0003-0205-6940](/media/client/orcid_16x16.png)
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.
References
Agarwal, A., Gupta, S., and Sharma, R. (2005). Oxidative stress and its implications in female infertility – a clinician’s perspective. Reprod. Biomed. Online 11, 641–650.| Oxidative stress and its implications in female infertility – a clinician’s perspective.Crossref | GoogleScholarGoogle Scholar | 16409717PubMed |
Ali, A. A., Bilodeau, J. F., and Sirard, M. A. (2003). Antioxidant requirements for bovine oocytes varies during in vitro maturation, fertilization and development. Theriogenology 59, 939–949.
| Antioxidant requirements for bovine oocytes varies during in vitro maturation, fertilization and development.Crossref | GoogleScholarGoogle Scholar | 12517395PubMed |
Anthony, P., Lowe, K. C., Davey, M. R., and Power, J. B. (1997). Synergistic effects of haemoglobin and Pluronic F-68 on mitotic division of cultured plant protoplasts. Adv. Exp. Med. Biol. 428, 477–481.
| Synergistic effects of haemoglobin and Pluronic F-68 on mitotic division of cultured plant protoplasts.Crossref | GoogleScholarGoogle Scholar | 9500087PubMed |
Basini, G., Bianco, F., Grasselli, F., Tirelli, M., Bussolati, S., and Tamanini, C. (2004). The effects of reduced oxygen tension on swine granulosa cell. Regul. Pept. 120, 69–75.
| The effects of reduced oxygen tension on swine granulosa cell.Crossref | GoogleScholarGoogle Scholar | 15177922PubMed |
Boland, N. I., Humpherson, P. G., Leese, H. J., and Gosden, R. G. (1993). Pattern of lactate production and steroidogenesis during growth and maturation of mouse ovarian follicles in vitro. Biol. Reprod. 48, 798–806.
| Pattern of lactate production and steroidogenesis during growth and maturation of mouse ovarian follicles in vitro.Crossref | GoogleScholarGoogle Scholar | 8485244PubMed |
Boland, N. I., Humpherson, P. G., Leese, H. J., and Gosden, R. G. (1994a). Characterization of follicular energy metabolism. Hum. Reprod. 9, 604–609.
| Characterization of follicular energy metabolism.Crossref | GoogleScholarGoogle Scholar | 8046010PubMed |
Boland, N. I., Humpherson, P. G., Leese, H. J., and Gosden, R. G. (1994b). The effect of glucose metabolism on murine follicle development and steroidogenesis in vitro. Hum. Reprod. 9, 617–623.
| The effect of glucose metabolism on murine follicle development and steroidogenesis in vitro.Crossref | GoogleScholarGoogle Scholar | 8046012PubMed |
Brown, H. M., Anastasi, M. R., Frank, L. A., Kind, K. L., Richani, D., Robker, R. L., Russell, D. L., Gilchrist, R. B., and Thompson, J. G. (2015). Hemoglobin: a gas transport molecule that is hormonally regulated in the ovarian follicle in mice and humans. Biol. Reprod. 92, 26.
| Hemoglobin: a gas transport molecule that is hormonally regulated in the ovarian follicle in mice and humans.Crossref | GoogleScholarGoogle Scholar | 25395682PubMed |
Connolly, J. M., Kane, M. T., Quinlan, L. R., Dockery, P., and Hynes, A. C. (2016). Hypoxia limits mouse follicle growth in vitro. Reprod. Fertil. Dev. 28, 1570–1579.
| Hypoxia limits mouse follicle growth in vitro.Crossref | GoogleScholarGoogle Scholar |
Cortvrindt, R., Smitz, J., and Van Steirteghem, A. C. (1996). In-vitro maturation, fertilization and embryo development of immature oocytes from early preantral follicles from prepubertal mice in a simplified culture system. Hum. Reprod. 11, 2656–2666.
| In-vitro maturation, fertilization and embryo development of immature oocytes from early preantral follicles from prepubertal mice in a simplified culture system.Crossref | GoogleScholarGoogle Scholar | 9021369PubMed |
Cortvrindt, R., Smitz, J., and Van Steirteghem, A. C. (1997). Assessment of the need for follicle stimulating hormone in early preantral mouse follicle culture in vitro. Hum. Reprod. 12, 759–768.
| Assessment of the need for follicle stimulating hormone in early preantral mouse follicle culture in vitro.Crossref | GoogleScholarGoogle Scholar | 9159439PubMed |
Dixon, H. B., and McIntosh, R. (1967). Reduction of methaemoglobin in haemoglobin samples using gel filtration for continuous removal of reaction products. Nature 213, 399–400.
| Reduction of methaemoglobin in haemoglobin samples using gel filtration for continuous removal of reaction products.Crossref | GoogleScholarGoogle Scholar | 6029528PubMed |
Eppig, J. J., and Downs, S. M. (1987). The effect of hypoxanthine on mouse oocyte growth and development in vitro: maintenance of meiotic arrest and gonadotropin-induced oocyte maturation. Dev. Biol. 119, 313–321.
| The effect of hypoxanthine on mouse oocyte growth and development in vitro: maintenance of meiotic arrest and gonadotropin-induced oocyte maturation.Crossref | GoogleScholarGoogle Scholar | 3100361PubMed |
Eppig, J. J., and O’Brien, M. J. (1996). Development in vitro of mouse oocytes from primordial follicles. Biol. Reprod. 54, 197–207.
| Development in vitro of mouse oocytes from primordial follicles.Crossref | GoogleScholarGoogle Scholar | 8838017PubMed |
Eppig, J. J., and Schroeder, A. C. (1989). Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation and fertilisation in vitro. Biol. Reprod. 41, 268–276.
| Capacity of mouse oocytes from preantral follicles to undergo embryogenesis and development to live young after growth, maturation and fertilisation in vitro.Crossref | GoogleScholarGoogle Scholar | 2508774PubMed |
Fennema, M., Zeilmaker, G., Faithfull, S., and Erdmann, W. (1986). Oxygen tension in the pre-ovulatory and non-ovulating ovarium follicle of the rat. Adv. Exp. Med. Biol. 200, 457–462.
| Oxygen tension in the pre-ovulatory and non-ovulating ovarium follicle of the rat.Crossref | GoogleScholarGoogle Scholar | 3799336PubMed |
Fischer, B., Künzel, W., Kleinstein, J., and Gips, H. (1992). Oxygen tension in follicular fluid falls with follicle maturation. Eur. J. Obstet. Gynecol. Reprod. Biol. 43, 39–43.
| Oxygen tension in follicular fluid falls with follicle maturation.Crossref | GoogleScholarGoogle Scholar | 1737607PubMed |
Gigli, I., Byrd, D. D., and Fortune, J. E. (2006). Effects of oxygen tension and supplements to the culture medium on activation and development of bovine follicles in vitro. Theriogenology 66, 344–353.
| Effects of oxygen tension and supplements to the culture medium on activation and development of bovine follicles in vitro.Crossref | GoogleScholarGoogle Scholar | 16442155PubMed |
Goffe, R. A., Shi, J. Y., and Nguyen, A. K. C. (1995). Media additives for high performance cell culture in hollow fiber bioreactors. In ‘Animal Cell Technology: Developments Towards the 21st Century’. (Eds E. C. Beuvery, J. B. Griffiths. and W. P. Zeijlemaker.) pp. 187–191. (Springer Netherlands: Dordrecht.)
Gook, D. A., Edgar, D. H., Lewis, K., Sheedy, J. R., and Gardner, D. K. (2014). Impact of oxygen concentration on adult murine pre-antral follicle development in vitro and the corresponding metabolic profile. Mol. Hum. Reprod. 20, 31–41.
| Impact of oxygen concentration on adult murine pre-antral follicle development in vitro and the corresponding metabolic profile.Crossref | GoogleScholarGoogle Scholar | 24013158PubMed |
Harris, S. E., Adriaens, I., Leese, H. J., Gosden, R. G., and Picton, H. M. (2007). Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro. Reproduction 134, 415–424.
| Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro.Crossref | GoogleScholarGoogle Scholar | 17709560PubMed |
Hinshelwood, M. M., Demeter-Arlotto, M., Means, G. D., and Simpson, E. R. (1994). Expression of genes encoding steroidogenic enzymes in the ovary. In ‘Molecular Biology of the Female Reproductive System’. (Ed. J. Findlay.) pp. 129–145. (Academic Press: London.)
Hornick, J. E., Duncan, F. E., Shea, L. D., and Woodruff, T. K. (2012). Isolated primate primordial follicles require a rigid physical environment to survive and grow in vitro. Hum. Reprod. 27, 1801–1810.
| Isolated primate primordial follicles require a rigid physical environment to survive and grow in vitro.Crossref | GoogleScholarGoogle Scholar | 22456922PubMed |
Hughes, A. F. (1950). The effect of inhibitory substances on cell division; a study on living cells in tissue cultures. Q. J. Microsc. Sci. 91, 251–277.
| 24539000PubMed |
Hütter, E., Renner, K., Jansen-Dürr, P., and Gnaiger, E. (2002). Biphasic oxygen kinetics of cellular respiration and linear oxygen dependence of antimycin A inhibited oxygen consumption. Mol. Biol. Rep. 29, 83–87.
| Biphasic oxygen kinetics of cellular respiration and linear oxygen dependence of antimycin A inhibited oxygen consumption.Crossref | GoogleScholarGoogle Scholar | 12241081PubMed |
Jensen, M. D., Wallach, D. F. H., and Sherwood, P. (1976). Diffusion in tissue cultures on gas-permeable and impermeable supports. J. Theor. Biol. 56, 443–458.
| Diffusion in tissue cultures on gas-permeable and impermeable supports.Crossref | GoogleScholarGoogle Scholar |
Koch, C. J. (1984). A thin-film culturing technique allowing rapid gas–liquid equilibration (6 sec) with no toxicity to mammalian cells. Radiat. Res. 97, 434–442.
| A thin-film culturing technique allowing rapid gas–liquid equilibration (6 sec) with no toxicity to mammalian cells.Crossref | GoogleScholarGoogle Scholar | 6695057PubMed |
Kreeger, P. K., Deck, J. W., Woodruff, T. K., and Shea, L. D. (2006). The in vitro regulation of ovarian follicle development using alginate–extracellular matrix gels. Biomaterials 27, 714–723.
| The in vitro regulation of ovarian follicle development using alginate–extracellular matrix gels.Crossref | GoogleScholarGoogle Scholar | 16076485PubMed |
Livak, K. J., and Schmittgen, T. D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25, 402–408.
| Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method.Crossref | GoogleScholarGoogle Scholar | 11846609PubMed |
Luvoni, G. C., Keskintepe, L., and Brackett, B. G. (1996). Improvement in bovine embryo production in vitro by glutathione-containing culture media. Mol. Reprod. Dev. 43, 437–443.
| Improvement in bovine embryo production in vitro by glutathione-containing culture media.Crossref | GoogleScholarGoogle Scholar | 9052934PubMed |
Macchiarelli, G. (2000). The microvasculature of the ovary: a review by SEM of vascular corrosion casts. J. Reprod. Dev. 46, 207–225.
| The microvasculature of the ovary: a review by SEM of vascular corrosion casts.Crossref | GoogleScholarGoogle Scholar |
Macchiarelli, G., Jiang, J.-Y., Nottola, S. A., and Sato, E. (2006). Morphological patterns of angiogenesis in ovarian follicle capillary networks. A scanning electron microscopy study of corrosion cast. Microsc. Res. Tech. 69, 459–468.
| Morphological patterns of angiogenesis in ovarian follicle capillary networks. A scanning electron microscopy study of corrosion cast.Crossref | GoogleScholarGoogle Scholar | 16718659PubMed |
Makanji, Y., Tagler, D., Pahnke, J., Shea, L. D., and Woodruff, T. K. (2014). Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival. Am. J. Physiol. Endocrinol. Metab. 306, E893–E903.
| Hypoxia-mediated carbohydrate metabolism and transport promote early-stage murine follicle growth and survival.Crossref | GoogleScholarGoogle Scholar | 24569591PubMed |
Mannello, F., and Tonti, G. A. (2007). Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold! Stem Cells 25, 1603–1609.
| Concise review: no breakthroughs for human mesenchymal and embryonic stem cell culture: conditioned medium, feeder layer, or feeder-free; medium with fetal calf serum, human serum, or enriched plasma; serum-free, serum replacement nonconditioned medium, or ad hoc formula? All that glitters is not gold!Crossref | GoogleScholarGoogle Scholar | 17395775PubMed |
McLaughlin, B. A., Nelson, D., Silver, I. A., Erecinska, M., and Chesselet, M. F. (1998). Methylmalonate toxicity in primary neuronal cultures. Neuroscience 86, 279–290.
| Methylmalonate toxicity in primary neuronal cultures.Crossref | GoogleScholarGoogle Scholar | 9692761PubMed |
McLaughlin, M., Albertini, D. F., Wallace, W. H. B., Anderson, R. A., and Telfer, E. E. (2018). Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system. Mol. Hum. Reprod. 24, 135–142.
| Metaphase II oocytes from human unilaminar follicles grown in a multi-step culture system.Crossref | GoogleScholarGoogle Scholar | 29390119PubMed |
McNatty, K. P. (1981). Hormonal correlates of follicular development in the human ovary. Aust. J. Biol. Sci. 34, 249–268.
| Hormonal correlates of follicular development in the human ovary.Crossref | GoogleScholarGoogle Scholar | 6794554PubMed |
Metzen, E., Wolff, M., Fandrey, J., and Jelkmann, W. (1995). Pericellular PO2 and O2 consumption in monolayer cell cultures. Respir. Physiol. 100, 101–106.
| Pericellular PO2 and O2 consumption in monolayer cell cultures.Crossref | GoogleScholarGoogle Scholar | 7624611PubMed |
Miller, W. L., and Bose, H. S. (2011). Early steps in steroidogenesis: intracellular cholesterol trafficking. J. Lipid Res. 52, 2111–2135.
| Early steps in steroidogenesis: intracellular cholesterol trafficking.Crossref | GoogleScholarGoogle Scholar | 21976778PubMed |
Mizunuma, H., Liu, X., Andoh, K., Abe, Y., Kobayashi, J., Yamada, K., Yokota, H., Ibuki, Y., and Hasegawa, Y. (1999). Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage. Endocrinology 140, 37–42.
| Activin from secondary follicles causes small preantral follicles to remain dormant at the resting stage.Crossref | GoogleScholarGoogle Scholar | 9886804PubMed |
Morimoto, Y., Oku, Y., Sonoda, M., Haruki, A., Ito, K., Hashimoto, S., and Fukuda, A. (2007). High oxygen atmosphere improves human follicle development in organ cultures of ovarian cortical tissues in vitro. Hum. Reprod. 22, 3170–3177.
| High oxygen atmosphere improves human follicle development in organ cultures of ovarian cortical tissues in vitro.Crossref | GoogleScholarGoogle Scholar | 17932085PubMed |
Nayudu, P. L., and Osborn, S. M. (1992). Factors influencing the rate of preantral and antral growth of mouse ovarian follicles in vitro. J. Reprod. Fertil. 95, 349–362.
| Factors influencing the rate of preantral and antral growth of mouse ovarian follicles in vitro.Crossref | GoogleScholarGoogle Scholar | 1517993PubMed |
Nayudu, P. L., Fehrenbach, A., Kiesel, P., Vitt, U. A., Pancharatna, K., and Osborn, S. (2001). Progress toward understanding follicle development in vitro: appearances are not deceiving. Arch. Med. Res. 32, 587–594.
| Progress toward understanding follicle development in vitro: appearances are not deceiving.Crossref | GoogleScholarGoogle Scholar | 11750734PubMed |
Neeman, M., Abramovitch, R., Schiffenbauer, Y. S., and Tempel, C. (1997). Regulation of angiogenesis by hypoxic stress: from solid tumours to the ovarian follicle. Int. J. Exp. Pathol. 78, 57–70.
| Regulation of angiogenesis by hypoxic stress: from solid tumours to the ovarian follicle.Crossref | GoogleScholarGoogle Scholar | 9203980PubMed |
O’Brien, M. J., Pendola, J. K., and Eppig, J. J. (2003). A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence. Biol. Reprod. 68, 1682–1686.
| A revised protocol for in vitro development of mouse oocytes from primordial follicles dramatically improves their developmental competence.Crossref | GoogleScholarGoogle Scholar | 12606400PubMed |
Palkowski, A., and Sikorski, A. F. (1993). Effect of hemin on growth and DNA synthesis of HL-60 cells. In Vitro Cell. Dev. Biol. Anim. 29, 679–682.
| Effect of hemin on growth and DNA synthesis of HL-60 cells.Crossref | GoogleScholarGoogle Scholar |
Qvist, R., Blackwell, L. F., Bourne, H., and Brown, J. B. (1990). Development of mouse ovarian follicles from primary to preovulatory stages in vitro. J. Reprod. Fertil. 89, 169–180.
| Development of mouse ovarian follicles from primary to preovulatory stages in vitro.Crossref | GoogleScholarGoogle Scholar | 2115582PubMed |
Redding, G. P., Bronlund, J. E., and Hart, A. L. (2006). The effects of IVF aspiration on the temperature, dissolved oxygen levels, and pH of follicular fluid. J. Assist. Reprod. Genet. 23, 37–40.
| The effects of IVF aspiration on the temperature, dissolved oxygen levels, and pH of follicular fluid.Crossref | GoogleScholarGoogle Scholar | 16538552PubMed |
Reitzer, L. J., Wice, B. M., and Kennell, D. (1979). Evidence that glutamine, not sugar, is the major energy source for cultured HeLa cells. J. Biol. Chem. 254, 2669–2676.
| 429309PubMed |
Richards, J. S., and Hedin, L. (1988). Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization. Annu. Rev. Physiol. 50, 441–463.
| Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization.Crossref | GoogleScholarGoogle Scholar | 3288100PubMed |
Riess, J. G. (2001). Oxygen carriers (‘blood substitutes’) – raison d’etre, chemistry, and some physiology. Chem. Rev. 101, 2797–2920.
| Oxygen carriers (‘blood substitutes’) – raison d’etre, chemistry, and some physiology.Crossref | GoogleScholarGoogle Scholar | 11749396PubMed |
Rose, U. M., Hanssen, R. G. J. M., and Kloosterboer, H. J. (1999). Development and characterization of an in vitro ovulation model using mouse ovarian follicles. Biol. Reprod. 61, 503–511.
| Development and characterization of an in vitro ovulation model using mouse ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 10411533PubMed |
Ryle, M. (1971). The time factor in responses to pituitary gonadotrophins by mouse ovaries in vitro. J. Reprod. Fertil. 25, 61–74.
| The time factor in responses to pituitary gonadotrophins by mouse ovaries in vitro.Crossref | GoogleScholarGoogle Scholar | 5551718PubMed |
Semenza, G. L. (1999). Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1. Annu. Rev. Cell Dev. Biol. 15, 551–578.
| Regulation of mammalian O2 homeostasis by hypoxia-inducible factor 1.Crossref | GoogleScholarGoogle Scholar | 10611972PubMed |
Shaw, J., and Trounson, A. (1997). Oncological implications in the replacement of ovarian tissue. Hum. Reprod. 12, 403–405.
| Oncological implications in the replacement of ovarian tissue.Crossref | GoogleScholarGoogle Scholar | 9130725PubMed |
Smith, S. M., and Schroedl, N. A. (1992). Heme-containing compounds replace chick embryo extract and enhance differentiation in avian muscle cell culture. In Vitro Cell. Dev. Biol. 28, 387–390.
| Heme-containing compounds replace chick embryo extract and enhance differentiation in avian muscle cell culture.Crossref | GoogleScholarGoogle Scholar |
Smitz, J. E. J., and Cortvrindt, R. G. (2002). The earliest stages of folliculogenesis in vitro. Reproduction 123, 185–202.
| The earliest stages of folliculogenesis in vitro.Crossref | GoogleScholarGoogle Scholar |
Smitz, J., Cortvrindt, R., and Van Steirteghem, A. C. (1996). Normal oxygen atmosphere is essential for the solitary long-term culture of early preantral mouse follicles. Mol. Reprod. Dev. 45, 466–475.
| Normal oxygen atmosphere is essential for the solitary long-term culture of early preantral mouse follicles.Crossref | GoogleScholarGoogle Scholar | 8956285PubMed |
Spears, N., Boland, N. I., Murray, A. A., and Gosden, R. G. (1994). Mouse oocytes derived from in vitro grown primary ovarian follicles are fertile. Hum. Reprod. 9, 527–532.
| Mouse oocytes derived from in vitro grown primary ovarian follicles are fertile.Crossref | GoogleScholarGoogle Scholar | 8006146PubMed |
Spears, N., Murray, A. A., Allison, V., Boland, N. I., and Gosden, R. G. (1998). Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro. J. Reprod. Fertil. 113, 19–26.
| Role of gonadotrophins and ovarian steroids in the development of mouse follicles in vitro.Crossref | GoogleScholarGoogle Scholar | 9713372PubMed |
Talevi, R., Sudhakaran, S., Barbato, V., Merolla, A., Braun, S., Di Nardo, M., Costanzo, V., Ferraro, R., Iannantuoni, N., Catapano, G., and Gualtieri, R. (2018). Is oxygen availability a limiting factor for in vitro folliculogenesis? PLoS One 13, e0192501.
| Is oxygen availability a limiting factor for in vitro folliculogenesis?Crossref | GoogleScholarGoogle Scholar | 29425251PubMed |
Thompson, J. G., Brown, H. M., Kind, K. L., and Russell, D. L. (2015). The ovarian antral follicle: living on the edge of hypoxia or not? Biol. Reprod. 92, 153.
| The ovarian antral follicle: living on the edge of hypoxia or not?Crossref | GoogleScholarGoogle Scholar | 25972011PubMed |
Tsai-Turton, M., and Luderer, U. (2006). Opposing effects of glutathione depletion and follicle-stimulating hormone on reactive oxygen species and apoptosis in cultured preovulatory rat follicles. Endocrinology 147, 1224–1236.
| Opposing effects of glutathione depletion and follicle-stimulating hormone on reactive oxygen species and apoptosis in cultured preovulatory rat follicles.Crossref | GoogleScholarGoogle Scholar | 16339198PubMed |
Umbreit, J. (2007). Methemoglobin – it’s not just blue: a concise review. Am. J. Hematol. 82, 134–144.
| Methemoglobin – it’s not just blue: a concise review.Crossref | GoogleScholarGoogle Scholar | 16986127PubMed |
Varghese, A. C., du Plessis, S. S., Falcone, T., and Agarwal, A. (2008). Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation. Reprod. Biol. Endocrinol. 6, 47.
| Cryopreservation/transplantation of ovarian tissue and in vitro maturation of follicles and oocytes: challenges for fertility preservation.Crossref | GoogleScholarGoogle Scholar | 18828928PubMed |
Verger, C., Sassa, S., and Kappas, A. (1983). Growth-promoting effects of iron- and cobalt- protoporphyrins on cultured embryonic cells. J. Cell. Physiol. 116, 135–141.
| Growth-promoting effects of iron- and cobalt- protoporphyrins on cultured embryonic cells.Crossref | GoogleScholarGoogle Scholar | 6863396PubMed |
Waters, S. M., Kelly, J. P., O’Boyle, P., Moloney, A. P., and Kenny, D. A. (2009). Effect of level and duration of dietary n-3 polyunsaturated fatty acid supplementation on the transcriptional regulation of Delta9-desaturase in muscle of beef cattle. J. Anim. Sci. 87, 244–252.
| Effect of level and duration of dietary n-3 polyunsaturated fatty acid supplementation on the transcriptional regulation of Delta9-desaturase in muscle of beef cattle.Crossref | GoogleScholarGoogle Scholar | 18791145PubMed |
Wenger, R. H., Kurtcuoglu, V., Scholz, C. C., Marti, H. H., and Hoogewijs, D. (2015). Frequently asked questions in hypoxia research. Hypoxia (Auckl.) 3, 35–43.
| Frequently asked questions in hypoxia research.Crossref | GoogleScholarGoogle Scholar | 27774480PubMed |
Wice, B. M., Reitzer, L. J., and Kennell, D. (1981). The continuous growth of vertebrate cells in the absence of sugar. J. Biol. Chem. 256, 7812–7819.
| 6790526PubMed |
Williams, J. A., Vincent, S. R., and Reiner, P. B. (1997). Nitric oxide production in rat thalamus changes with behavioral state, local depolarization, and brainstem stimulation. J. Neurosci. 17, 420–427.
| Nitric oxide production in rat thalamus changes with behavioral state, local depolarization, and brainstem stimulation.Crossref | GoogleScholarGoogle Scholar | 8987767PubMed |
Wolff, M., Fandrey, J., and Jelkmann, W. (1993). Microelectrode measurements of pericellular PO2 in erythropoietin-producing human hepatoma cell cultures. Am. J. Physiol. 265, C1266–C1270.
| Microelectrode measurements of pericellular PO2 in erythropoietin-producing human hepatoma cell cultures.Crossref | GoogleScholarGoogle Scholar | 8238479PubMed |
Wycherley, G., Downey, D., Kane, M. T., and Hynes, A. C. (2004). A novel follicle culture system markedly increases follicle volume, cell number and oestradiol secretion. Reproduction 127, 669–677.
| A novel follicle culture system markedly increases follicle volume, cell number and oestradiol secretion.Crossref | GoogleScholarGoogle Scholar | 15175503PubMed |
Wycherley, G., Kane, M. T., and Hynes, A. C. (2005). Oxidative phosphorylation and the tricarboxylic acid cycle are essential for normal development of mouse ovarian follicles. Hum. Reprod. 20, 2757–2763.
| Oxidative phosphorylation and the tricarboxylic acid cycle are essential for normal development of mouse ovarian follicles.Crossref | GoogleScholarGoogle Scholar | 16006477PubMed |
Xiao, S., Zhang, J., Romero, M. M., Smith, K. N., Shea, L. D., and Woodruff, T. K. (2015). In vitro follicle growth supports human oocyte meiotic maturation. Sci. Rep. 5, 17323.
| In vitro follicle growth supports human oocyte meiotic maturation.Crossref | GoogleScholarGoogle Scholar | 26612176PubMed |
Xu, M., Kreeger, P. K., Shea, L. D., and Woodruff, T. K. (2006). Tissue-engineered follicles produce live, fertile offspring. Tissue Eng. 12, 2739–2746.
| Tissue-engineered follicles produce live, fertile offspring.Crossref | GoogleScholarGoogle Scholar | 17518643PubMed |
Xu, M., West-Farrell, E. R., Stouffer, R. L., Shea, L. D., Woodruff, T. K., and Zelinski, M. B. (2009). Encapsulated three-dimensional culture supports development of nonhuman primate secondary follicles. Biol. Reprod. 81, 587–594.
| Encapsulated three-dimensional culture supports development of nonhuman primate secondary follicles.Crossref | GoogleScholarGoogle Scholar | 19474063PubMed |