The variable success of in vitro maturation: can we do better?
The efficiency of in vitro assisted reproductive technologies, consisting of the transfer of embryos obtained in vitro through in vitro maturation, in vitro fertilization and early embryo culture is still limited. The quality of the oocytes is pivotal for assisted reproductive efficiency and the maturation of the oocyte represents the first key limiting step of the in vitro embryo production system. At the time of removal from the antral follicles, the oocyte is still completing the final growth and differentiation steps, needed to provide the so-called developmental competence, i.e. the machinery required to sustain fertilization and embryo development. In mono-ovular species only one oocyte per cycle is available for procreation, therefore the current assisted reproduction techniques strive to overcome this natural boundary. However, the success is still limited and overall the effectiveness does not exceed the efficiency achieved in millions of years of mammalian evolution. One of the problems lies in the intrinsic heterogeneity of the oocytes that are subjected to in vitro maturation and in the lack of dedicated in vitro approaches to finalize the differentiation process. In this review we will try to overview some of the salient aspects of current practices by emphasizing the most critical and fundamental features in oocyte differentiation that should be carefully considered for improving current techniques.
Adams GP, Jaiswal R, Singh J, Malhi P. 2008. Progress in understanding ovarian follicular dynamics in cattle. Theriogenology, 69:72-80.
Adona PR, Pires PR, Quetglas MD, Schwarz KR, Leal CL. 2008. Prematuration of bovine oocytes with butyrolactone. I: effects on meiosis progression, cytoskeleton, organelle distribution and embryo development. Anim Reprod Sci, 108:49-65.
Albuz FK, Sasseville M, Lane M, Armstrong DT, Thompson JG, Gilchrist RB. 2010. Simulated physiological oocyte maturation (SPOM): a novel in vitro maturation system that substantially improves embryo yield and pregnancy outcomes. Hum Reprod, 25:2999-3011.
Anderson E, Albertini DF. 1976. Gap junctions between the oocyte and companion follicle cells in the mammalian ovary. J Cell Biol, 71:680-686.
Atef A, Paradis F, Vigneault C, Sirard MA. 2005. The potential role of gap junction communication between cumulus cells and bovine oocytes during in vitro maturation. Mol Reprod Dev, 71:358-367.
Azari-Dolatabad N, Rahmani HR, Hajian M, Ostadhosseini S, Hosseini SM, Nasr-Esfahani MH. 2016. Effects of cilostamide and/or forskolin on the meiotic resumption and development competence of growing ovine oocytes selected by brilliant cresyl blue staining. Theriogenology, 85:1483-1490.
Bilodeau-Goeseels S. 2012. Bovine oocyte meiotic inhibition before in vitro maturation and its value to in vitro embryo production: does it improve developmental competence? Reprod Domest Anim, 47:687-693.
Blondin P, Sirard MA. 1995. Oocyte and follicular morphology as determining characteristics for developmental competence in bovine oocytes. Mol Reprod Dev, 41:54-62.
Blondin P, Coenen K, Guilbault LA, Sirard MA. 1997. In vitro production of bovine embryos: developmental competence is acquired before maturation. Theriogenology, 47:1061-1075.
Bornslaeger EA, Schultz RM. 1985. Regulation of mouse oocyte maturation: effect of elevating cumulus cell cAMP on oocyte cAMP levels. Biol Reprod, 33:698-704.
Bouniol-Baly C, Hamraoui L, Guibert J, Beaujean N, Szollosi MS, Debey P. 1999. Differential transcriptional activity associated with chromatin configuration in fully grown mouse germinal vesicle oocytes. Biol Reprod, 60:580-587.
Cho WK, Stern S, Biggers JD. 1974. Inhibitory effect
of dibutyryl cAMP on mouse oocyte maturation in vitro. J Exp Zool, 187:383-386.
Combelles CM, Albertini DF, Racowsky C. 2003. Distinct microtubule and chromatin characteristics of human oocytes after failed in-vivo and in-vitro meiotic maturation. Hum Reprod, 18:2124-2130.
Conti M. 2002. Specificity of the cyclic adenosine 3',5'-monophosphate signal in granulosa cell function. Biol Reprod, 67:1653-1661.
Conti M, Hsieh M, Zamah AM, Oh JS. 2012. Novel signaling mechanisms in the ovary during oocyte maturation and ovulation. Mol Cell Endocrinol, 356:65-73.
Conti M, Franciosi F. 2018. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum Reprod Update, 24:245-266.
De Bem TH, Chiaratti MR, Rochetti R, Bressan FF, Sangalli JR, Miranda MS, Pires PR, Schwartz KR, Sampaio RV, Fantinato-Neto P, Pimentel JR, Perecin F, Smith LC, Meirelles FV, Adona PR, Leal CL. 2011. Viable calves produced by somatic cell nuclear transfer using meiotic-blocked oocytes. Cell Reprogram, 13:419-429.
De La Fuente R. 2006. Chromatin modifications in the germinal vesicle (GV) of mammalian oocytes. Dev Biol, 292:1-12.
De Loos FA, Zeinstra E, Bevers MM. 1994. Follicular wall maintains meiotic arrest in bovine oocytes cultured in vitro. Mol Reprod Dev, 39:162-165.
Dekel N, Beers WH. 1978. Rat oocyte maturation in vitro: relief of cyclic AMP inhibition by gonadotropins. Proc Natl Acad Sci USA, 75:4369-4373.
Dieci C, Lodde V, Franciosi F, Lagutina I, Tessaro I, Modina SC, Albertini DF, Lazzari G, Galli C, Luciano AM. 2013. The effect of cilostamide on gap junction communication dynamics, chromatin remodeling, and competence acquisition in pig oocytes following parthenogenetic activation and nuclear transfer. Biol Reprod, 89:68. doi: 10.1095/biolreprod.113.110577.
Dieci C, Lodde V, Labreque R, Dufort I, Tessaro I, Sirard MA, Luciano AM. 2016. Differences in cumulus cell gene expression indicate the benefit of a pre-maturation step to improve in-vitro bovine embryo production. Mol Hum Reprod, 22:882-897.
Dieleman SJ, Hendriksen PJ, Viuff D, Thomsen PD, Hyttel P, Knijn HM, Wrenzycki C, Kruip TA, Niemann H, Gadella BM, Bevers MM, Vos PL. 2002. Effects of in vivo prematuration and in vivo final maturation on developmental capacity and quality of pre-implantation embryos. Theriogenology, 57:5-20.
Diogenes MN, Guimaraes ALS, Leme LO, Mauricio MF, Dode MAN. 2017. Effect of prematuration and maturation with fibroblast growth factor 10 (FGF10) on in vitro development of bovine oocytes. Theriogenology, 102:190-198.
Donnay I, Faerge I, Grondahl C, Verhaeghe B, Sayoud H, Ponderato N, Galli C, Lazzari G. 2004. Effect of prematuration, meiosis activating sterol and enriched maturation medium on the nuclear maturation and competence to development of calf oocytes. Theriogenology, 62:1093-1107.
Fair T, Hyttel P, Greve T. 1995. Bovine oocyte diameter in relation to maturational competence and transcriptional activity. Mol Reprod Dev, 42:437-442.
Ferreira EM, Vireque AA, Adona PR, Ferriani RA, Navarro PA. 2009. Prematuration of bovine oocytes with butyrolactone I reversibly arrests meiosis without increasing meiotic abnormalities after in vitro maturation. Eur J Obstet Gynecol Reprod Biol, 145:76-80.
Fortune JE. 1994. Ovarian follicular growth and development in mammals. Biol Reprod, 50:225-232.
Fouladi Nashta AA, Waddington D, Campbell KH. 1998. Maintenance of bovine oocytes in meiotic arrest and subsequent development In vitro: A comparative evaluation of antral follicle culture with other methods. Biol Reprod, 59:255-262.
Franciosi F, Coticchio G, Lodde V, Tessaro I, Modina SC, Fadini R, Dal Canto M, Renzini MM, Albertini DF, Luciano AM. 2014. Natriuretic peptide precursor C delays meiotic resumption and sustains gap junction-mediated communication in bovine cumulus-enclosed oocytes. Biol Reprod, 91:61. doi: 10.1095/biolreprod.114.118869.
Galli C. 2017. Achievements and unmet promises of assisted reproduction technologies in large animals: a per-sonal perspective. Anim Reprod, 14:614-621.
Gharibi S, Hajian M, Ostadhosseini S, Hosseini SM, Forouzanfar M, Nasr-Esfahani MH. 2013. Effect of phosphodiesterase type 3 inhibitor on nuclear maturation and in vitro development of ovine oocytes. Theriogenology, 80:302-312.
Gilchrist RB, Luciano AM, Richani D, Zeng HT, Wang X, Vos MD, Sugimura S, Smitz J, Richard FJ, Thompson JG. 2016. Oocyte maturation and quality: role of cyclic nucleotides. Reproduction, 152:R143-157.
Guimaraes AL, Pereira SA, Leme LO, Dode MA. 2015. Evaluation of the simulated physiological oocyte maturation system for improving bovine in vitro embryo production. Theriogenology, 83:52-57.
Guixue Z, Luciano AM, Coenen K, Gandolfi F, Sirard MA. 2001. The influence of cAMP before or during bovine oocyte maturation on embryonic developmental competence. Theriogenology, 55:1733-1743.
Hyttel P, Fair T, Callesen H, Greve T. 1997. Oocyte growth, capacitation and final maturation in cattle. Theriogenology, 47:23-32.
Imai K, Kobayashi S, Kaneyama K, Kojima T, Nagai T. 2002. Effects of butyrolactone-I on GVBD in bovine oocytes and subsequent maturation, fertilization and development in vitro. J Reprod Dev, 48:249-255.
Jee BC, Chen HY, Chian RC. 2009. Effect of a phosphodiesterase type 3 inhibitor in oocyte maturation medium on subsequent mouse embryo development. Fertil Steril, 91(5 suppl):2037-2042.
Jones KT. 2004. Turning it on and off: M-phase promoting factor during meiotic maturation and fertilization. Mol Hum Reprod, 10:1-5.
Kitagawa M, Okabe T, Ogino H, Matsumoto H, Suzuki-Takahashi I, Kokubo T, Higashi H, Saitoh S, Taya Y, Yasuda H, et al. 1993. Butyrolactone I, a
selective inhibitor of cdk2 and cdc2 kinase. Oncogene, 8:2425-2432.
Kubelka M, Motlik J, Schultz RM, Pavlok A. 2000. Butyrolactone I reversibly inhibits meiotic maturation of bovine oocytes,without influencing chromosome condensation activity. Biol Reprod, 62:292-302.
Labrecque R, Lodde V, Dieci C, Tessaro I, Luciano AM, Sirard MA. 2015. Chromatin remodelling and histone mRNA accumulation in bovine germinal vesicle oocytes. Mol Reprod Dev, 82:450-462.
Leibfried L, First NL. 1980. Effect of bovine and porcine follicular fluid and granulosa cells on maturation of oocytes in vitro. Biol Reprod, 23:699-704.
Li HJ, Sutton-McDowall ML, Wang X, Sugimura S, Thompson JG, Gilchrist RB. 2016. Extending prematuration with cAMP modulators enhances the cumulus contribution to oocyte antioxidant defence and oocyte quality via gap junctions. Hum Reprod, 31:810-821.
Lodde V, Modina S, Galbusera C, Franciosi F, Luciano AM. 2007. Large-scale chromatin remodeling in germinal vesicle bovine oocytes: interplay with gap junction functionality and developmental competence. Mol Reprod Dev, 74:740-749.
Lodde V, Modina S, Maddox-Hyttel P, Franciosi F, Lauria A, Luciano AM. 2008. Oocyte morphology and transcriptional silencing in relation to chromatin remodeling during the final phases of bovine oocyte growth. Mol Reprod Dev, 75:915-924.
Lodde V, Modina SC, Franciosi F, Zuccari E, Tessaro I, Luciano AM. 2009. Localization of DNA methyltransferase-1 during oocyte differentiation, in vitro maturation and early embryonic development in cow. Eur J Histochem, 53:199-207.
Lodde V, Franciosi F, Tessaro I, Modina SC, Luciano AM. 2013. Role of gap junction-mediated communications in regulating large-scale chromatin configuration remodeling and embryonic developmental competence acquisition in fully grown bovine oocyte. J Assist Reprod Genet, 30:1219-1226.
Lodde V, Luciano AM, Franciosi F, Labrecque R, Sirard MA. 2017. Accumulation of chromatin remodelling enzyme and histone transcripts in bovine oocytes. Results Probl Cell Differ, 63:223-255.
Lonergan P, Dinnyes A, Fair T, Yang X, Boland M. 2000. Bovine oocyte and embryo development following meiotic inhibition with butyrolactone I. Mol Reprod Dev, 57:204-209.
Lonergan P, Faerge I, Hyttel PM, Boland M, Fair T. 2003. Ultrastructural modifications in bovine oocytes maintained in meiotic arrest in vitro using roscovitine or butyrolactone. Mol Reprod Dev, 64:369-378.
Lonergan P, Fair T. 2008. In vitro-produced bovine embryos: dealing with the warts. Theriogenology, 69:17-22.
Luciano AM, Peluso JJ. 1995. Effect of in vivo gonadotropin treatment on the ability of progesterone, estrogen, and cyclic adenosine 5'-monophosphate to inhibit insulin-dependent granulosa cell mitosis in vitro. Biol Reprod, 53:664-669.
Luciano AM, Pocar P, Milanesi E, Modina S, Rieger D, Lauria A, Gandolfi F. 1999. 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, 54:86-91.
Luciano AM, Modina S, Vassena R, Milanesi E, Lauria A, Gandolfi F. 2004. Role of intracellular cyclic adenosine 3',5'-monophosphate concentration and oocyte-cumulus cells communications on the acquisition of the developmental competence during in vitro maturation of bovine oocyte. Biol Reprod, 70:465-472.
Luciano AM, Lodde V, Beretta MS, Colleoni S, Lauria A, Modina S. 2005. Developmental capability of denuded bovine oocyte in a co-culture system with intact cumulus-oocyte complexes: role of cumulus cells, cyclic adenosine 3',5'-monophosphate, and glutathione. Mol Reprod Dev, 71:389-397.
Luciano AM, Franciosi F, Modina SC, Lodde V. 2011. Gap junction-mediated communications regulate chromatin remodeling during bovine oocyte growth and differentiation through cAMP-dependent mechanism(s). Biol Reprod, 85:1252-1259.
Luciano AM, Lodde V. 2013. Changes of large-scale chromatin configuration during mammalian oocyte differentiation. In: Coticchio G, Albertini DF, De Santis L (Ed.). Oogenesis. London: Springer. pp. 93-108.
Luciano AM, Franciosi F, Dieci C, Lodde V. 2014. Changes in large-scale chromatin structure and function during oogenesis: a journey in company with follicular cells. Anim Reprod Sci, 149:3-10.
Luciano AM, Sirard MA. 2018. Successful in vitro maturation of oocytes: a matter of follicular differentiation. Biol Reprod, 98:162-169.
Lussier JG, Matton P, Dufour JJ. 1987. Growth rates of follicles in the ovary of the cow. J Reprod Fertil, 81:301-307.
Marchal R, Tomanek M, Terqui M, Mermillod P. 2001. Effects of cell cycle dependent kinases inhibitor on nuclear and cytoplasmic maturation of porcine oocytes. Mol Reprod Dev, 60:65-73.
Mehlmann LM, Jones TL, Jaffe LA. 2002. Meiotic arrest in the mouse follicle maintained by a Gs protein in the oocyte. Science, 297(5585):1343-1345.
Mehlmann LM. 2005. Stops and starts in mammalian oocytes: recent advances in understanding the regulation of meiotic arrest and oocyte maturation. Reproduction, 130:791-799.
Meijer L, Borgne A, Mulner O, Chong JP, Blow JJ, Inagaki N, Inagaki M, Delcros JG, Moulinoux JP. 1997. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Eur J Biochem, 243:527-536.
Mermillod P, Marchal R. 1999. [Oocyte of domestic mammals: a model for the study of in vitro maturation]. Contracept Fertil Sex, 27:440-448.
Mermillod P, Tomanek M, Marchal R, Meijer L. 2000. High developmental competence of cattle oocytes maintained at the germinal vesicle stage for 24 hours in culture by specific inhibition of MPF kinase activity. Mol Reprod Dev, 55:89-95.
Merton JS, de Roos AP, Mullaart E, de Ruigh L,
Kaal L, Vos PL, Dieleman SJ. 2003. Factors affecting oocyte quality and quantity in commercial application of embryo technologies in the cattle breeding industry. Theriogenology, 59:651-674.
Miyara F, Migne C, Dumont-Hassan M, Le Meur A, Cohen-Bacrie P, Aubriot FX, Glissant A, Nathan C, Douard S, Stanovici A, Debey P. 2003. Chromatin configuration and transcriptional control in human and mouse oocytes. Mol Reprod Dev 64:458-470.
Modina S, Luciano AM, Vassena R, Baraldi-Scesi L, Lauria A, Gandolfi F. 2001. Oocyte developmental competence after in vitro maturation depends on the persistence of cumulus-oocyte comunications which are linked to the intracellular concentration of cAMP. Ital J Anat Embryol, 106(2 suppl. 2):241-248.
Nogueira D, Ron-El R, Friedler S, Schachter M, Raziel A, Cortvrindt R, Smitz J. 2006. Meiotic arrest in vitro by phosphodiesterase 3-inhibitor enhances maturation capacity of human oocytes and allows subsequent embryonic development. Biol Reprod, 74:177-184.
Nogueira D, Vanhoutte L. 2009. Use of phosphodiesterase type 3 inhibitor to improve IVM outcome: experimental set up matters. Fertil Steril, 91(5):e3; author reply e4-5. doi.org/10.1016/j.fertnstert. 2008.12.110.
Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA. 2009. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development, 136:1869-1878.
Ozawa M, Nagai T, Somfai T, Nakai M, Maedomari N, Fahrudin M, Karja NW, Kaneko H, Noguchi J, Ohnuma K, Yoshimi N, Miyazaki H, Kikuchi K. 2008. Comparison between effects of 3-isobutyl-1-methylxanthine and FSH on gap junctional communication, LH-receptor expression, and meiotic maturation of cumulus-oocyte complexes in pigs. Mol Reprod Dev, 75:857-866.
Park B, Lee H, Lee Y, Elahi F, Lee J, Lee ST, Park CK, Hyun SH, Lee E. 2016. Cilostamide and forskolin treatment during pre-IVM improves preimplantation development of cloned embryos by influencing meiotic progression and gap junction communication in pigs. Theriogenology, 86:757-765.
Pincus G, Enzmann EV. 1935. The comparative behavior of mammalian eggs in vivo and in vitro. I. The activation of ovarian eggs. J Exp Med, 62:665-675.
Ponderato N, Lagutina I, Crotti G, Turini P, Galli C, Lazzari G. 2001. Bovine oocytes treated prior to in vitro maturation with a combination of butyrolactone I and roscovitine at low doses maintain a normal developmental capacity. Mol Reprod Dev, 60:579-585.
Ponderato N, Crotti G, Turini P, Duchi R, Galli C, Lazzari G. 2002. Embryonic and foetal development of bovine oocytes treated with a combination of butyrolactone I and roscovitine in an enriched medium prior to IVM and IVF. Mol Reprod Dev, 62:513-518.
Richani D, Wang X, Zeng HT, Smitz J, Thompson JG, Gilchrist RB. 2014. Pre-maturation with cAMP modulators in conjunction with EGF-like peptides during in vitro maturation enhances mouse oocyte developmental competence. Mol Reprod Dev, 81:422-435.
Richard FJ, Sirard MA. 1996. Effects of follicular cells on oocyte maturation. II: Theca cell inhibition of bovine oocyte maturation in vitro. Biol Reprod, 54:22-28.
Richard S, Baltz JM. 2014. Prophase I arrest of mouse oocytes mediated by natriuretic peptide precursor C requires GJA1 (connexin-43) and GJA4 (connexin-37) gap junctions in the antral follicle and cumulus-oocyte complex. Biol Reprod, 90:137. doi: 10.1095/biolreprod. 114.118505.
Robinson JW, Zhang M, Shuhaibar LC, Norris RP, Geerts A, Wunder F, Eppig JJ, Potter LR, Jaffe LA. 2012. Luteinizing hormone reduces the activity of the NPR2 guanylyl cyclase in mouse ovarian follicles, contributing to the cyclic GMP decrease that promotes resumption of meiosis in oocytes. Dev Biol, 366:308-316.
Romero S, Sanchez F, Lolicato F, Van Ranst H, Smitz J. 2016. Immature oocytes from unprimed juvenile mice become a valuable source for embryo production when using C-type natriuretic peptide as essential component of culture medium. Biol Reprod, 95:64. doi: 10.1095/biolreprod.116.139808.
Rose RD, Gilchrist RB, Kelly JM, Thompson JG, Sutton-McDowall ML. 2013. Regulation of sheep oocyte maturation using cAMP modulators. Theriogenology, 79:142-148.
Sa Barretto LS, Castro VS, Garcia JM, Mingoti GZ. 2011. Meiotic inhibition of bovine oocytes in medium supplemented with a serum replacer and hormones: effects on meiosis progression and developmental capacity. Zygote, 19:107-116.
Sanchez F, Romero S, De Vos M, Verheyen G, Smitz J. 2015. Human cumulus-enclosed germinal vesicle oocytes from early antral follicles reveal heterogeneous cellular and molecular features associated with in vitro maturation capacity. Hum Reprod, 30:1396-1409.
Sanchez F, Lolicato F, Romero S, De Vos M, Van Ranst H, Verheyen G, Anckaert E, Smitz JEJ. 2017. An improved IVM method for cumulus-oocyte complexes from small follicles in polycystic ovary syndrome patients enhances oocyte competence and embryo yield. Hum Reprod, 32:2056-2068.
Shu YM, Zeng HT, Ren Z, Zhuang GL, Liang XY, Shen HW, Yao SZ, Ke PQ, Wang NN. 2008. Effects of cilostamide and forskolin on the meiotic resumption and embryonic development of immature human oocytes. Hum Reprod, 23:504-513.
Sirard MA, Bilodeau S. 1990. Granulosa cells inhibit the resumption of meiosis in bovine oocytes in vitro. Biol Reprod, 43:777-783.
Sirard MA, Coenen K. 1993. The co-culture of cumulus-enclosed bovine oocytes and hemi-sections of follicles: Effects on meiotic resumption. Theriogenology, 40:933-942.
Soares ACS, Lodde V, Barros RG, Price CA, Luciano AM, Buratini J. 2017. Steroid hormones interact with natriuretic peptide C to delay nuclear maturation, to maintain oocyte-cumulus communication and to improve the quality of in vitro-produced embryos
in cattle. Reprod Fertil Dev, 29:2217-2224.
Thomas RE, Thompson JG, Armstrong DT, Gilchrist RB. 2004. Effect of specific phosphodiesterase isoenzyme inhibitors during in vitro maturation of bovine oocytes on meiotic and developmental capacity. Biol Reprod, 71:1142-1149.
Tsafriri A, Chun SY, Zhang R, Hsueh AJ, Conti M. 1996. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol, 178:393-402.
Vaccari S, Weeks JL, 2nd, Hsieh M, Menniti FS, Conti M. 2009. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod, 81:595-604.
Vanhoutte L, De Sutter P, Nogueira D, Gerris J, Dhont M, Van der Elst J. 2007. Nuclear and cytoplasmic maturation of in vitro matured human oocytes after temporary nuclear arrest by phosphodiesterase 3-inhibitor. Hum Reprod, 22:1239-1246.
Wang L, Jiang X, Wu Y, Lin J, Zhang L, Yang N, Huang J. 2016. Effect of milrinone on the developmental competence of growing lamb oocytes identified with brilliant cresyl blue. Theriogenology, 86:2020-2027.
Wu GM, Sun QY, Mao J, Lai L, McCauley TC, Park KW, Prather RS, Didion BA, Day BN. 2002. High developmental competence of pig oocytes after meiotic inhibition with a specific M-phase promoting factor kinase inhibitor, butyrolactone I. Biol Reprod, 67:170-177.
Zeng HT, Ren Z, Guzman L, Wang X, Sutton-McDowall ML, Ritter LJ, De Vos M, Smitz J, Thompson JG, Gilchrist RB. 2013. Heparin and cAMP modulators interact during pre-in vitro maturation to affect mouse and human oocyte meiosis and developmental competence. Hum Reprod, 28:1536-1545.
Zeng HT, Richani D, Sutton-McDowall ML, Ren Z, Smitz JE, Stokes Y, Gilchrist RB, Thompson JG. 2014. Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes. Biol Reprod, 91:47. doi: 10.1095/biolreprod.114.118471.
Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. 2010. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science, 330(6002):366-369.
Zhang M, Su YQ, Sugiura K, Wigglesworth K, Xia G, Eppig JJ. 2011. Estradiol promotes and maintains cumulus cell expression of natriuretic peptide receptor 2 (NPR2) and meiotic arrest in mouse oocytes in vitro. Endocrinology, 152:4377-4385.
Zuccotti M, Piccinelli A, Giorgi Rossi P, Garagna S, Redi CA. 1995. Chromatin organization during mouse oocyte growth. Mol Reprod Dev, 41:479-485.