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Reevaluation and evolution of the simulated physiological oocyte maturation system
Theriogenology 84 (2015) 656–657
Contents lists available at ScienceDirect
Theriogenology journal homepage: www.theriojournal.com
Letter to the Editor
Reevaluation and evolution of the simulated physiological oocyte maturation system Simulated physiological oocyte maturation (SPOM) is an oocyte IVM system that attempts to recapitulate in vitro, some of the biochemical and cellular events that occur naturally during oocyte maturation in vivo, to improve the efficiency and utility of IVM [1,2]. Hence, there has been considerable interest in SPOM, particularly for cattle artificial breeding and human infertility treatment. Recently, Guimarães et al. [3] evaluated SPOM and found it to be ineffective at improving subsequent bovine in vitro embryo development. Initially Guimarães et al. [3] attempted to incorporate SPOM into their own IVM and embryo production system (e.g., retaining serum and porcine FSH). The authors subsequently attempted a number of modifications of the SPOM IVM system, all to no avail. Indeed, the difficulty that Guimarães et al. [3] reported when working with SPOM version 1 (SPOMv1) is consistent with our own experiences at times and also that of other groups. Within our own laboratory, we have found that subtle changes in SPOM methodology can have major adverse outcomes on oocyte meiotic maturation and embryo yield, making SPOMv1 unreliable to work with. When we adapted the SPOMv1 protocol to ovine oocytes, we saw no significant effect (positive or negative) on blastocyst rates but an improvement in blastocyst quality [4]. In a major venture to develop SPOMv1 for human clinical IVM, we found that under certain oocyte collection and maturation conditions, oocyte maturation was substantially blocked [5]. After some time, we uncovered an unexpected adverse interaction between heparin in the oocyte collection medium and high cAMP in pre-IVM. This knowledge led us to develop SPOM version 2 (SPOMv2; see in the following) [5]. Using SPOMv1 with bovine oocytes, Ulloa et al. [6] produced significantly fewer blastocysts compared to standard IVM, although those generated were of comparable quality and interestingly may exhibit a DNA methylation pattern more akin to in vivo–matured oocytes than in vitro– matured oocytes. Most recently, using SPOMv1 Buell et al. [7] were successfully able to delay ovine oocyte meiotic kinetics but found no notable improvement in parthenogenetic embryo production. Hence, in general, attempts by our own and other groups to adapt SPOMv1 to differing practical scenarios have proven frustrating and often disappointing. DOI of original article: http://dx.doi.org/10.1016/j.theriogenology. 2014.07.042. 0093-691X/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.theriogenology.2015.03.032
The principal downside of SPOMv1 is that it has not proven to be a robust oocyte maturation system under differing laboratory and field conditions. We view SPOMv1 as a delicately balanced oocyte maturation system, whereby the balance between meiotic inhibitors, meiotic inducers, and oocyte meiotic kinetics is finely poised and the cAMP modulators controlling these processes are sensitive to factors which we are yet to fully understand. When the system is correctly tuned, it generates high-quality oocytes leading to substantial improvements in embryo and fetal yield. However, subtle variations in culture conditions (base IVM medium), choice of serum versus BSA, potency of FSH, and actual experimental protocol, and so forth, appear to have major effects on the efficacy of SPOMv1. For example, we have determined that washing cumulus–oocyte complexes (COCs) at the end of the pre-IVM period (usually 2 hours) before transfer to IVM is critical, and failure to wash thoroughly leading to transfer of small quantities of forskolin and 3-isobutyl-1-methylxanthine into the IVM phase has major effects on oocyte meiotic kinetics which can affect fertilization rates and embryo yield if care is not taken. Hence, when attempting to adopt SPOMv1 into a new environment or species, it is important to examine the kinetics of oocyte meiosis to determine when oocytes are reaching metaphase II under the user’s culture conditions. However, such requirements are usually laborious and impractical in a clinical or commercial scenario. In light of these practical difficulties, we have modified the SPOM system and developed a version 2 protocol. In SPOMv2, the pre-IVM step remains unchanged, but in the IVM phase, cilostamide is omitted and oocyte maturation is only slightly extended [5,8,9]. Because COCs retain high levels of cAMP from pre-IVM, meiotic resumption is delayed but progresses nonetheless possibly because of meiotic induction by EGFlike peptides whose expression is induced by forskolin [8]. Prolonging pre-IVM (e.g., 2–4 hours for mouse COCs) appears advantageous [8]. A recent study has confirmed that a variant on the protocol improves mouse embryo yield [10]. In many respects, this modified SPOMv2 protocol has many of the hallmarks of other cAMP-modulating IVM systems that contain some form of pre-IVM and that have proven to increase oocyte developmental competence [11–13]. Further refinement of such cAMP-mediated pre-IVM systems stands to bring on-going improvements in the efficiency of IVM.
Letter to the Editor / Theriogenology 84 (2015) 656–657
657
Acknowledgments
References
This work was supported by the National Health and Medical Research Council of Australia through Project Grants (1007551, 1076004, 1062762) and Senior Research Fellowships (1023210, 627007); and by grants from Cook Medical.
[1] Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod 2010;25:2999–3011. [2] Gilchrist RB. Recent insights into oocyte-follicle cell interactions provide opportunities for the development of new approaches to in vitro maturation. Reprod Fertil Dev 2011;23:23–31. [3] Guimaraes AL, Pereira SA, Leme LO, Dode MA. Evaluation of the simulated physiological oocyte maturation system for improving bovine in vitro embryo production. Theriogenology 2015;83:52–7. [4] Rose RD, Gilchrist RB, Kelly JM, Thompson JG, Sutton-McDowall ML. Regulation of sheep oocyte maturation using cAMP modulators. Theriogenology 2013;79:142–8. [5] Zeng HT, Ren Z, Guzman L, Wang X, Sutton-McDowall ML, Ritter LJ, et al. Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence. Hum Reprod 2013;28:1536–45. [6] Ulloa SM, Heinzmann J, Herrmann D, Timmermann B, Baulain U, Grossfeld R, et al. Effects of different oocyte retrieval and in vitro maturation systems on bovine embryo development and quality. Zygote 2014;23:367–77. [7] Buell M, Chitwood JL, Ross PJ. cAMP modulation during sheep in vitro oocyte maturation delays progression of meiosis without affecting oocyte parthenogenetic developmental competence. Anim Reprod Sci 2015;154:16–24. [8] Richani D, Wang X, Zeng HT, Smitz J, Thompson JG, Gilchrist RB. Prematuration with cAMP modulators in conjunction with EGF-like peptides during in vitro maturation enhances mouse oocyte developmental competence. Mol Reprod Dev 2014;81:422–35. [9] Zeng HT, Richani D, Sutton-McDowall ML, Ren Z, Smitz JE, Stokes Y, et al. Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes. Biol Reprod 2014;91:47. [10] Santiquet NW, Greene AF, Schoolcraft WB, Krisher RL. Pre-in vitro maturation with cyclic AMP and cyclic GMP modulators improves developmental competence of mouse oocytes. Reprod Fertil Dev 2014;27:245. [11] Funahashi H, Cantley TC, Day BN. Synchronization of meiosis in porcine oocytes by exposure to dibutyryl cyclic adenosine monophosphate improves developmental competence following in vitro fertilization. Biol Reprod 1997;57:49–53. [12] Guixue Z, Luciano AM, Coenen K, Gandolfi F, Sirard MA. The influence of cAMP before or during bovine oocyte maturation on embryonic developmental competence. Theriogenology 2001;55: 1733–43. [13] Luciano AM, Pocar P, Milanesi E, Modina S, Rieger D, Lauria A, et al. Effect of different levels of intracellular cAMP on the in vitro maturation of cattle oocytes and their subsequent development following in vitro fertilization. Mol Reprod Dev 1999;54:86–91.
R.B. Gilchrist* Discipline of Obstetrics and Gynaecology, School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia * Corresponding author. Tel.: þ61 2 93852562; fax: þ61 2 93852573. E-mail address: [email protected] (R.B. Gilchrist) H.T. Zeng Center for Reproductive Medicine, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China X. Wang Department of Obstetrics and Gynaecology, St George Public Hospital, Sydney, New South Wales, Australia D. Richani Discipline of Obstetrics and Gynaecology, School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia J. Smitz Research Group Follicle Biology, Vrije Universiteit Brussel, Brussels, Belgium J.G. Thompson School of Paediatrics and Reproductive Health, Robinson Research Institute, The University of Adelaide, South Australia, Australia Received 20 March 2015 Available online 2 April 2015
Contents lists available at ScienceDirect
Theriogenology journal homepage: www.theriojournal.com
Letter to the Editor
Reevaluation and evolution of the simulated physiological oocyte maturation system Simulated physiological oocyte maturation (SPOM) is an oocyte IVM system that attempts to recapitulate in vitro, some of the biochemical and cellular events that occur naturally during oocyte maturation in vivo, to improve the efficiency and utility of IVM [1,2]. Hence, there has been considerable interest in SPOM, particularly for cattle artificial breeding and human infertility treatment. Recently, Guimarães et al. [3] evaluated SPOM and found it to be ineffective at improving subsequent bovine in vitro embryo development. Initially Guimarães et al. [3] attempted to incorporate SPOM into their own IVM and embryo production system (e.g., retaining serum and porcine FSH). The authors subsequently attempted a number of modifications of the SPOM IVM system, all to no avail. Indeed, the difficulty that Guimarães et al. [3] reported when working with SPOM version 1 (SPOMv1) is consistent with our own experiences at times and also that of other groups. Within our own laboratory, we have found that subtle changes in SPOM methodology can have major adverse outcomes on oocyte meiotic maturation and embryo yield, making SPOMv1 unreliable to work with. When we adapted the SPOMv1 protocol to ovine oocytes, we saw no significant effect (positive or negative) on blastocyst rates but an improvement in blastocyst quality [4]. In a major venture to develop SPOMv1 for human clinical IVM, we found that under certain oocyte collection and maturation conditions, oocyte maturation was substantially blocked [5]. After some time, we uncovered an unexpected adverse interaction between heparin in the oocyte collection medium and high cAMP in pre-IVM. This knowledge led us to develop SPOM version 2 (SPOMv2; see in the following) [5]. Using SPOMv1 with bovine oocytes, Ulloa et al. [6] produced significantly fewer blastocysts compared to standard IVM, although those generated were of comparable quality and interestingly may exhibit a DNA methylation pattern more akin to in vivo–matured oocytes than in vitro– matured oocytes. Most recently, using SPOMv1 Buell et al. [7] were successfully able to delay ovine oocyte meiotic kinetics but found no notable improvement in parthenogenetic embryo production. Hence, in general, attempts by our own and other groups to adapt SPOMv1 to differing practical scenarios have proven frustrating and often disappointing. DOI of original article: http://dx.doi.org/10.1016/j.theriogenology. 2014.07.042. 0093-691X/$ – see front matter Ó 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.theriogenology.2015.03.032
The principal downside of SPOMv1 is that it has not proven to be a robust oocyte maturation system under differing laboratory and field conditions. We view SPOMv1 as a delicately balanced oocyte maturation system, whereby the balance between meiotic inhibitors, meiotic inducers, and oocyte meiotic kinetics is finely poised and the cAMP modulators controlling these processes are sensitive to factors which we are yet to fully understand. When the system is correctly tuned, it generates high-quality oocytes leading to substantial improvements in embryo and fetal yield. However, subtle variations in culture conditions (base IVM medium), choice of serum versus BSA, potency of FSH, and actual experimental protocol, and so forth, appear to have major effects on the efficacy of SPOMv1. For example, we have determined that washing cumulus–oocyte complexes (COCs) at the end of the pre-IVM period (usually 2 hours) before transfer to IVM is critical, and failure to wash thoroughly leading to transfer of small quantities of forskolin and 3-isobutyl-1-methylxanthine into the IVM phase has major effects on oocyte meiotic kinetics which can affect fertilization rates and embryo yield if care is not taken. Hence, when attempting to adopt SPOMv1 into a new environment or species, it is important to examine the kinetics of oocyte meiosis to determine when oocytes are reaching metaphase II under the user’s culture conditions. However, such requirements are usually laborious and impractical in a clinical or commercial scenario. In light of these practical difficulties, we have modified the SPOM system and developed a version 2 protocol. In SPOMv2, the pre-IVM step remains unchanged, but in the IVM phase, cilostamide is omitted and oocyte maturation is only slightly extended [5,8,9]. Because COCs retain high levels of cAMP from pre-IVM, meiotic resumption is delayed but progresses nonetheless possibly because of meiotic induction by EGFlike peptides whose expression is induced by forskolin [8]. Prolonging pre-IVM (e.g., 2–4 hours for mouse COCs) appears advantageous [8]. A recent study has confirmed that a variant on the protocol improves mouse embryo yield [10]. In many respects, this modified SPOMv2 protocol has many of the hallmarks of other cAMP-modulating IVM systems that contain some form of pre-IVM and that have proven to increase oocyte developmental competence [11–13]. Further refinement of such cAMP-mediated pre-IVM systems stands to bring on-going improvements in the efficiency of IVM.
Letter to the Editor / Theriogenology 84 (2015) 656–657
657
Acknowledgments
References
This work was supported by the National Health and Medical Research Council of Australia through Project Grants (1007551, 1076004, 1062762) and Senior Research Fellowships (1023210, 627007); and by grants from Cook Medical.
[1] Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod 2010;25:2999–3011. [2] Gilchrist RB. Recent insights into oocyte-follicle cell interactions provide opportunities for the development of new approaches to in vitro maturation. Reprod Fertil Dev 2011;23:23–31. [3] Guimaraes AL, Pereira SA, Leme LO, Dode MA. Evaluation of the simulated physiological oocyte maturation system for improving bovine in vitro embryo production. Theriogenology 2015;83:52–7. [4] Rose RD, Gilchrist RB, Kelly JM, Thompson JG, Sutton-McDowall ML. Regulation of sheep oocyte maturation using cAMP modulators. Theriogenology 2013;79:142–8. [5] Zeng HT, Ren Z, Guzman L, Wang X, Sutton-McDowall ML, Ritter LJ, et al. Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence. Hum Reprod 2013;28:1536–45. [6] Ulloa SM, Heinzmann J, Herrmann D, Timmermann B, Baulain U, Grossfeld R, et al. Effects of different oocyte retrieval and in vitro maturation systems on bovine embryo development and quality. Zygote 2014;23:367–77. [7] Buell M, Chitwood JL, Ross PJ. cAMP modulation during sheep in vitro oocyte maturation delays progression of meiosis without affecting oocyte parthenogenetic developmental competence. Anim Reprod Sci 2015;154:16–24. [8] Richani D, Wang X, Zeng HT, Smitz J, Thompson JG, Gilchrist RB. Prematuration with cAMP modulators in conjunction with EGF-like peptides during in vitro maturation enhances mouse oocyte developmental competence. Mol Reprod Dev 2014;81:422–35. [9] Zeng HT, Richani D, Sutton-McDowall ML, Ren Z, Smitz JE, Stokes Y, et al. Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes. Biol Reprod 2014;91:47. [10] Santiquet NW, Greene AF, Schoolcraft WB, Krisher RL. Pre-in vitro maturation with cyclic AMP and cyclic GMP modulators improves developmental competence of mouse oocytes. Reprod Fertil Dev 2014;27:245. [11] Funahashi H, Cantley TC, Day BN. Synchronization of meiosis in porcine oocytes by exposure to dibutyryl cyclic adenosine monophosphate improves developmental competence following in vitro fertilization. Biol Reprod 1997;57:49–53. [12] Guixue Z, Luciano AM, Coenen K, Gandolfi F, Sirard MA. The influence of cAMP before or during bovine oocyte maturation on embryonic developmental competence. Theriogenology 2001;55: 1733–43. [13] Luciano AM, Pocar P, Milanesi E, Modina S, Rieger D, Lauria A, et al. Effect of different levels of intracellular cAMP on the in vitro maturation of cattle oocytes and their subsequent development following in vitro fertilization. Mol Reprod Dev 1999;54:86–91.
R.B. Gilchrist* Discipline of Obstetrics and Gynaecology, School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia * Corresponding author. Tel.: þ61 2 93852562; fax: þ61 2 93852573. E-mail address: [email protected] (R.B. Gilchrist) H.T. Zeng Center for Reproductive Medicine, Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China X. Wang Department of Obstetrics and Gynaecology, St George Public Hospital, Sydney, New South Wales, Australia D. Richani Discipline of Obstetrics and Gynaecology, School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia J. Smitz Research Group Follicle Biology, Vrije Universiteit Brussel, Brussels, Belgium J.G. Thompson School of Paediatrics and Reproductive Health, Robinson Research Institute, The University of Adelaide, South Australia, Australia Received 20 March 2015 Available online 2 April 2015