Animal Reproduction (AR)
Animal Reproduction (AR)
Congress Paper

DNA methylation, environmental exposures and early embryo development

Mélanie Breton-Larrivée, Elizabeth Elder, Serge McGraw

Downloads: 7
Views: 1698


The first crucial step in the developmental program occurs during pre-implantation, the time after the oocyte has been fertilized and before the embryo implants in the uterus. This period represents a vulnerable window as the epigenome undergoes dynamic changes in DNA methylation profiles. Alterations in the early embryonic reprogramming wave can impair DNA methylation patterns and induce permanent changes to the developmental program, leading to the onset of adverse health outcomes in offspring. Although there is an increasing body of evidence indicating that harmful exposures during preimplantation embryo development can trigger lasting epigenetic alterations in offspring, the mechanisms are still not fully understood. Since physiological or pathological changes in DNA methylation can occur as a response to environmental cues, proper environmental milieu plays a critical role in the success of embryonic development. In this review, we depict the mechanisms behind the embryonic epigenetic reprogramming of DNA methylation and highlight how maternal environmental stressors (e.g., alcohol, heat stress, nutrient availability) during pre-implantation and assisted reproductive technology procedures affect development and DNA methylation marks.


epigenetics, DNA methylation, preimplantation embryos, prenatal exposures, developmental programming.


Adam MP. 2012. The all-or-none phenomenon revisited. Birth Defects Res A Clin Mol Teratol, 94:664-669.

Anckaert E, De Rycke M, Smitz J. 2013. Culture of oocytes and risk of imprinting defects. Hum Reprod Update, 19:52-66.

Antequera F, Bird A. 1993. Number of CpG islands and genes in human and mouse. Proc Natl Acad Sci U S A, 90:11995-11999.

Arita K, Ariyoshi M, Tochio H, Nakamura Y, Shirakawa M. 2008. Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism. Nature, 455:818-821.

Avvakumov GV, Walker JR, Xue S, Li Y, Duan S, Bronner C, Arrowsmith CH, Dhe-Paganon S. 2008. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature, 455:822-825.

Barski A, Cuddapah S, Cui K, Roh TY, Schones DE, Wang Z, Wei G, Chepelev I, Zhao K. 2007. High-resolution profiling of histone methylations in the human genome. Cell, 129:823-837.

Berntsen S, Soderstrom-Anttila V, Wennerholm UB, Laivuori H, Loft A, Oldereid NB, Romundstad LB, Bergh C, Pinborg A. 2019. The health of children conceived by ART: 'the chicken or the egg?'. Hum Reprod Update, 25:137-158.

Bielawski DM, Zaher FM, Svinarich DM, Abel EL2002. Paternal alcohol exposure affects sperm cytosine methyltransferase messenger RNA levels. Alcohol Clin Exp Res, 26:347-351.

Bird A. 2002. DNA methylation patterns and epigenetic memory. Genes Dev, 16:6-21.

Bonsch D, Lenz B, Fiszer R, Frieling H, Kornhuber J, Bleich S. 2006. Lowered DNA methyltransferase (DNMT-3b) mRNA expression is associated with genomic DNA hypermethylation in patients with chronic alcoholism. J Neural Transm (Vienna), 113:1299-1304.

Bostick M, Kim JK, Esteve PO, Clark A, Pradhan S, Jacobsen SE. 2007. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science, 317:1760-1764.

Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. 2009. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med, 180:462-467.

Canovas S, Ivanova E, Romar R, Garcia-Martinez S, Soriano-Ubeda C, Garcia-Vazquez FA, Saadeh H, Andrews S, Kelsey G, Coy P. 2017. DNA methylation and gene expression changes derived from assisted reproductive technologies can be decreased by reproductive fluids. Elife, 6.

Checiu M, Sandor S. 1986. The effect of ethanol upon early development in mice and rats. IX. Late effect of acute preimplantation intoxication in mice. Morphol Embryol (Bucur), 32:5-11.

Chen Z, Hagen DE, Elsik CG, Ji T, Morris CJ, Moon LE, Rivera RM. 2015. Characterization of global loss of imprinting in fetal overgrowth syndrome induced by assisted reproduction. Proc Natl Acad Sci U S A, 112:4618-4623.

Chen Z, Robbins KM, Wells KD, Rivera RM. 2013. Large offspring syndrome: a bovine model for the human loss-of-imprinting overgrowth syndrome Beckwith-Wiedemann. Epigenetics, 8:591-601.

Choufani S, Turinsky AL, Melamed N, Greenblatt E, Brudno M, Berard A, Fraser WD, Weksberg R, Trasler J, Monnier P. 2019. Impact of assisted reproduction, infertility, sex and paternal factors on the placental DNA methylome. Hum Mol Genet, 28:372-385.

Choux C, Binquet C, Carmignac V, Bruno C, Chapusot C, Barberet J, Lamotte M, Sagot P, Bourc'his D, Fauque P. 2018. The epigenetic control of transposable elements and imprinted genes in newborns is affected by the mode of conception: ART versus spontaneous conception without underlying infertility. Hum Reprod, 33:331-340.

Chudley AE, Conry J, Cook JL, Loock C, Rosales T, LeBlanc N. 2005. Fetal alcohol spectrum disorder: Canadian guidelines for diagnosis. Cmaj, 172:S1-s21.

Cook JL, Green CR, Lilley CM, Anderson SM, Baldwin ME, Chudley AE, Conry JL, LeBlanc N, Loock CA, Lutke J, Mallon BF, McFarlane AA, Temple VK, Rosales T. 2016. Fetal alcohol spectrum disorder: a guideline for diagnosis across the lifespan. Cmaj, 188:191-197.

Dasmahapatra AK, Khan IA. 2015. DNA methyltransferase expressions in Japanese rice fish (Oryzias latipes) embryogenesis is developmentally regulated and modulated by ethanol and 5-azacytidine. Comp Biochem Physiol C Toxicol Pharmacol, 176-177:1-9.

Davis TL, Yang GJ, McCarrey JR, Bartolomei MS. 2000. The H19 methylation imprint is erased and re-established differentially on the parental alleles during male germ cell development. Hum Mol Genet, 9:2885-2894.

de Barros FRO, Paula-Lopes FF. 2018. Cellular and epigenetic changes induced by heat stress in bovine preimplantation embryos. Mol Reprod Dev, 85:810-820.

Denomme MM, Zhang L, Mann MR. 2011. Embryonic imprinting perturbations do not originate from superovulation-induced defects in DNA methylation acquisition. Fertil Steril, 96:734-738.e732.

Derakhshan-Horeh M, Abolhassani F, Jafarpour F, Moini A, Karbalaie K, Hosseini SM, Nasr-Esfahani MH. 2016. Vitrification at Day3 stage appears not to affect the methylation status of H19/IGF2 differentially methylated region of in vitro produced human blastocysts. Cryobiology, 73:168-174.

DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, Dow-Edwards D, Hurd YL. 2011. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry, 70:763-769.

Duranthon V, Chavatte-Palmer P. 2018. Long term effects of ART: What do animals tell us? Mol Reprod Dev, 85:348-368.

El Hajj N, Haaf T. 2013. Epigenetic disturbances in in vitro cultured gametes and embryos: implications for human assisted reproduction. Fertil Steril, 99:632-641.

Fazakas-Todea I, Sandor S, Hateganu M, Perta D, Checiu I, Stefanescu S. 1986. The effect of ethanol upon early development in mice and rats. X. The effect of acute intoxication with some alcoholic beverages upon preimplantation development in rats. Morphol Embryol (Bucur), 32:159-164.

Ferguson-Smith AC. 2011. Genomic imprinting: the emergence of an epigenetic paradigm. Nat Rev Genet, 12:565-575.

Fitzpatrick GV, Soloway PD, Higgins MJ. 2002. Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet, 32:426-431.

Fortier AL, Lopes FL, Darricarrere N, Martel J, Trasler JM. 2008. Superovulation alters the expression of imprinted genes in the midgestation mouse placenta. Hum Mol Genet, 17:1653-1665.

Fortier AL, McGraw S, Lopes FL, Niles KM, Landry M, Trasler JM. 2014. Modulation of imprinted gene expression following superovulation. Mol Cell Endocrinol, 388:51-57.

Garro AJ, McBeth DL, Lima V, Lieber CS. 1991. Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res, 15:395-398.

Gibney ER, Nolan CM. 2010. Epigenetics and gene expression. Heredity (Edinb), 105:4-13.

Goll MG, Bestor TH. 2005. Eukaryotic cytosine methyltransferases. Annu Rev Biochem, 74:481-514.

Guerrero-Preston R, Goldman LR, Brebi-Mieville P, Ili-Gangas C, Lebron C, Witter FR, Apelberg BJ, Hernandez-Roystacher M, Jaffe A, Halden RU, Sidransky D. 2010. Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds. Epigenetics, 5:539-546.

Haycock PC, Ramsay M. 2009. Exposure of mouse embryos to ethanol during preimplantation development: effect on DNA methylation in the h19 imprinting control region. Biol Reprod, 81:618-627.

Henikoff S, Shilatifard A. 2011. Histone modification: cause or cog? Trends Genet, 27:389-396.

Hirasawa R, Chiba H, Kaneda M, Tajima S, Li E, Jaenisch R, Sasaki H. 2008. Maternal and zygotic Dnmt1 are necessary and sufficient for the maintenance of DNA methylation imprints during preimplantation development. Genes Dev, 22:1607-1616.

Howell CY, Bestor TH, Ding F, Latham KE, Mertineit C, Trasler JM, Chaillet JR. 2001. Genomic imprinting disrupted by a maternal effect mutation in the Dnmt1 gene. Cell, 104:829-838.

Howell CY, Steptoe AL, Miller MW, Chaillet JR. 1998. cis-Acting signal for inheritance of imprinted DNA methylation patterns in the preimplantation mouse embryo. Mol Cell Biol, 18:4149-4156.

Ideraabdullah FY, Vigneau S, Bartolomei MS. 2008. Genomic imprinting mechanisms in mammals. Mutat Res, 647:77-85.

Ito S, D'Alessio AC, Taranova OV, Hong K, Sowers LC, Zhang Y. 2010. Role of Tet proteins in 5mC to 5hmC conversion, ES-cell self-renewal and inner cell mass specification. Nature, 466:1129-1133.

Jenuwein T, Allis CD. 2001. Translating the histone code. Science, 293:1074-1080.

Jones PA. 2012. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet, 13:484-492.

Kagiwada S, Kurimoto K, Hirota T, Yamaji M, Saitou M. 2013. Replication-coupled passive DNA demethylation for the erasure of genome imprints in mice. Embo j, 32:340-353.

Kishikawa S, Murata T, Ugai H, Yamazaki T, Yokoyama KK. 2003. Control elements of Dnmt1 gene are regulated in cell-cycle dependent manner. Nucleic Acids Res Suppl:307-308.

Koch CM, Andrews RM, Flicek P, Dillon SC, Karaoz U, Clelland GK, Wilcox S, Beare DM, Fowler JC, Couttet P, James KD, Lefebvre GC, Bruce AW, Dovey OM, Ellis PD, Dhami P, Langford CF, Weng Z, Birney E, Carter NP, Vetrie D, Dunham I. 2007. The landscape of histone modifications across 1% of the human genome in five human cell lines. Genome Res, 17:691-707.

Kono T, Obata Y, Yoshimzu T, Nakahara T, Carroll J. 1996. Epigenetic modifications during oocyte growth correlates with extended parthenogenetic development in the mouse. Nat Genet, 13:91-94.

Koyama H, Ikeda S, Sugimoto M, Kume S. 2012. Effects of Folic Acid on the Development and Oxidative Stress of Mouse Embryos Exposed to Heat Stress. Reproduction in Domestic Animals, 47:921-927.

Legault LM, Bertrand-Lehouillier V, McGraw S. 2018. Pre-implantation alcohol exposure and developmental programming of FASD: an epigenetic perspective. Biochem Cell Biol, 96:117-130.

Lei H, Oh SP, Okano M, Juttermann R, Goss KA, Jaenisch R, Li E. 1996. De novo DNA cytosine methyltransferase activities in mouse embryonic stem cells. Development, 122:3195-3205.

Leonhardt H, Page AW, Weier HU, Bestor TH. 1992. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell, 71:865-873.

Li E, Bestor TH, Jaenisch R. 1992. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell, 69:915-926.

Li E. 2002. Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet, 3:662-673.

Lister R, Mukamel EA, Nery JR, Urich M, Puddifoot CA, Johnson ND, Lucero J, Huang Y, Dwork AJ, Schultz MD, Yu M, Tonti-Filippini J, Heyn H, Hu S, Wu JC, Rao A, Esteller M, He C, Haghighi FG, Sejnowski TJ, Behrens MM, Ecker JR. 2013. Global epigenomic reconfiguration during mammalian brain development. Science, 341:1237905.

Ma Y, Ma Y, Wen L, Lei H, Chen S, Wang X. 2019. Changes in DNA methylation and imprinting disorders in E9.5 mouse fetuses and placentas derived from vitrified eight-cell embryos. Mol Reprod Dev, 86:404-415.

Marikawa Y, Alarcon VB. 2009. Establishment of trophectoderm and inner cell mass lineages in the mouse embryo. Mol Reprod Dev, 76:1019-1032.

Market-Velker BA, Fernandes AD, Mann MR. 2010. Side-by-side comparison of five commercial media systems in a mouse model: suboptimal in vitro culture interferes with imprint maintenance. Biol Reprod, 83:938-950.

Marsit CJ. 2015. Influence of environmental exposure on human epigenetic regulation. J Exp Biol, 218:71-79.

McGraw S, Oakes CC, Martel J, Cirio MC, de Zeeuw P, Mak W, Plass C, Bartolomei MS, Chaillet JR, Trasler JM. 2013. Loss of DNMT1o disrupts imprinted X chromosome inactivation and accentuates placental defects in females. PLoS Genet, 9:e1003873.

McGraw S, Trasler J. 2013. Oocyte epigenetics and the risks for imprinting disorders associated with assisted reproduction. . Biology & Pathology of the Oocyte 2nd Edition, Cambridge University Press.

McGraw S, Zhang JX, Farag M, Chan D, Caron M, Konermann C, Oakes CC, Mohan KN, Plass C, Pastinen T, Bourque G, Chaillet JR, Trasler JM. 2015. Transient DNMT1 suppression reveals hidden heritable marks in the genome. Nucleic Acids Res, 43:1485-1497.

Morbeck DE, Baumann NA, Oglesbee D. 2017. Composition of single-step media used for human embryo culture. Fertil Steril, 107:1055-1060.e1051.

Morbeck DE, Krisher RL, Herrick JR, Baumann NA, Matern D, Moyer T. 2014a. Composition of commercial media used for human embryo culture. Fertil Steril, 102:759-766.e759.

Morbeck DE, Paczkowski M, Fredrickson JR, Krisher RL, Hoff HS, Baumann NA, Moyer T, Matern D. 2014b. Composition of protein supplements used for human embryo culture. J Assist Reprod Genet, 31:1703-1711.

Morey L, Santanach A, Di Croce L. 2015. Pluripotency and Epigenetic Factors in Mouse Embryonic Stem Cell Fate Regulation. Mol Cell Biol, 35:2716-2728.

Niakan KK, Han J, Pedersen RA, Simon C, Pera RA. 2012. Human pre-implantation embryo development. Development, 139:829-841.

Norouzitallab P, Baruah K, Vanrompay D, Bossier P. 2019. Can epigenetics translate environmental cues into phenotypes? Sci Total Environ, 647:1281-1293.

Novikova SI, He F, Bai J, Cutrufello NJ, Lidow MS, Undieh AS. 2008. Maternal cocaine administration in mice alters DNA methylation and gene expression in hippocampal neurons of neonatal and prepubertal offspring. PLoS One, 3:e1919.

Ohbo K, Tomizawa S. 2015. Epigenetic regulation in stem cell development, cell fate conversion, and reprogramming. Biomol Concepts, 6:1-9.

Okano M, Bell DW, Haber DA, Li E. 1999. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell, 99:247-257.

Pacis A, Mailhot-Leonard F, Tailleux L, Randolph HE, Yotova V, Dumaine A, Grenier JC, Barreiro LB. 2019. Gene activation precedes DNA demethylation in response to infection in human dendritic cells. Proc Natl Acad Sci U S A, 116:6938-6943.

Padmanabhan R, Hameed MS. 1988. Effects of acute doses of ethanol administered at pre-implantation stages on fetal development in the mouse. Drug Alcohol Depend, 22:91-100.

Page-Lariviere F, Campagna C, Sirard MA. 2017. Mechanisms Involved in Porcine Early Embryo Survival following Ethanol Exposure. Toxicol Sci, 156:289-299.

Patil V, Ward RL, Hesson LB. 2014. The evidence for functional non-CpG methylation in mammalian cells. Epigenetics, 9:823-828.

Plasschaert RN, Bartolomei MS. 2014. Genomic imprinting in development, growth, behavior and stem cells. Development, 141:1805-1813.

Pradhan S, Bacolla A, Wells RD, Roberts RJ. 1999. Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. J Biol Chem, 274:33002-33010.

Qin J, Liu X, Sheng X, Wang H, Gao S. 2016. Assisted reproductive technology and the risk of pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies: a meta-analysis of cohort studies. Fertil Steril, 105:73-85.e71-76.

Razin A, Cedar H. 1991. DNA methylation and gene expression. Microbiol Rev, 55:451-458.

Red-Horse K, Zhou Y, Genbacev O, Prakobphol A, Foulk R, McMaster M, Fisher SJ. 2004. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface. J Clin Invest, 114:744-754.

Reik W, Dean W, Walter J. 2001. Epigenetic reprogramming in mammalian development. Science, 293:1089-1093.

Saxonov S, Berg P, Brutlag DL. 2006. A genome-wide analysis of CpG dinucleotides in the human genome distinguishes two distinct classes of promoters. Proc Natl Acad Sci U S A, 103:1412-1417.

Seisenberger S, Peat JR, Hore TA, Santos F, Dean W, Reik W. 2013. Reprogramming DNA methylation in the mammalian life cycle: building and breaking epigenetic barriers. Philos Trans R Soc Lond B Biol Sci, 368:20110330.

Severin PM, Zou X, Gaub HE, Schulten K. 2011. Cytosine methylation alters DNA mechanical properties. Nucleic Acids Res, 39:8740-8751.

Smith ZD, Meissner A. 2013. DNA methylation: roles in mammalian development. Nat Rev Genet, 14:204-220.

Stoger R, Kubicka P, Liu CG, Kafri T, Razin A, Cedar H, Barlow DP. 1993. Maternal-specific methylation of the imprinted mouse Igf2r locus identifies the expressed locus as carrying the imprinting signal. Cell, 73:61-71.

Suetake I, Shinozaki F, Miyagawa J, Takeshima H, Tajima S. 2004. DNMT3L stimulates the DNA methylation activity of Dnmt3a and Dnmt3b through a direct interaction. J Biol Chem, 279:27816-27823.

Suter M, Abramovici A, Showalter L, Hu M, Shope CD, Varner M, Aagaard-Tillery K. 2010. In utero tobacco exposure epigenetically modifies placental CYP1A1 expression. Metabolism, 59:1481-1490.

Tahiliani M, Koh KP, Shen Y, Pastor WA, Bandukwala H, Brudno Y, Agarwal S, Iyer LM, Liu DR, Aravind L, Rao A. 2009. Conversion of 5-methylcytosine to 5-hydroxymethylcytosine in mammalian DNA by MLL partner TET1. Science, 324:930-935.

Thorvaldsen JL, Duran KL, Bartolomei MS. 1998. Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev, 12:3693-3702.

Toledo-Rodriguez M, Lotfipour S, Leonard G, Perron M, Richer L, Veillette S, Pausova Z, Paus T. 2010. Maternal smoking during pregnancy is associated with epigenetic modifications of the brain-derived neurotrophic factor-6 exon in adolescent offspring. Am J Med Genet B Neuropsychiatr Genet, 153b:1350-1354.

Toro R, Leonard G, Lerner JV, Lerner RM, Perron M, Pike GB, Richer L, Veillette S, Pausova Z, Paus T. 2008. Prenatal exposure to maternal cigarette smoking and the adolescent cerebral cortex. Neuropsychopharmacology, 33:1019-1027.

Ueda T, Abe K, Miura A, Yuzuriha M, Zubair M, Noguchi M, Niwa K, Kawase Y, Kono T, Matsuda Y, Fujimoto H, Shibata H, Hayashizaki Y, Sasaki H. 2000. The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development. Genes Cells, 5:649-659.

Urrego R, Rodriguez-Osorio N, Niemann H. 2014. Epigenetic disorders and altered gene expression after use of Assisted Reproductive Technologies in domestic cattle. Epigenetics, 9:803-815.

Uysal F, Ozturk S, Akkoyunlu G. 2018. Superovulation alters DNA methyltransferase protein expression in mouse oocytes and early embryos. J Assist Reprod Genet, 35:503-513.

Varela-Rey M, Woodhoo A, Martinez-Chantar ML, Mato JM, Lu SC. 2013. Alcohol, DNA methylation, and cancer. Alcohol Res, 35:25-35.

Vougiouklakis T, Nakamura Y, Saloura V. 2017. Critical roles of protein methyltransferases and demethylases in the regulation of embryonic stem cell fate. Epigenetics, 12:1015-1027.

Weber M, Schubeler D. 2007. Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol, 19:273-280.

Wehby GL, Prater K, McCarthy AM, Castilla EE, Murray JC. 2011. The Impact of Maternal Smoking during Pregnancy on Early Child Neurodevelopment. J Hum Cap, 5:207-254.

Weinerman R. 2018. In vitro fertilization (IVF): Where are we now? Birth Defects Res, 110:623-624.

White CR, Denomme MM, Tekpetey FR, Feyles V, Power SG, Mann MR. 2015. High Frequency of Imprinted Methylation Errors in Human Preimplantation Embryos. Sci Rep, 5:17311.

Wiebold JL, Becker WC. 1987. In-vivo and in-vitro effects of ethanol on mouse preimplantation embryos. J Reprod Fertil, 80:49-57.

Wu H, Zhang Y. 2014. Reversing DNA methylation: mechanisms, genomics, and biological functions. Cell, 156:45-68.

Young LE, Sinclair KD, Wilmut I. 1998. Large offspring syndrome in cattle and sheep. Rev Reprod, 3:155-163.

Zhu H, Wang G, Qian J. 2016a. Transcription factors as readers and effectors of DNA methylation. Nat Rev Genet, 17:551-565.

Zhu JQ, Liu JH, Liang XW, Xu BZ, Hou Y, Zhao XX, Sun QY. 2008. Heat stress causes aberrant DNA methylation of H19 and Igf-2r in mouse blastocysts. Mol Cells, 25:211-215.

Zhu L, Zhang Y, Liu Y, Zhang R, Wu Y, Huang Y, Liu F, Li M, Sun S, Xing L, Zhu Y, Chen Y, Xu L, Zhou L, Huang H, Zhang D. 2016b. Maternal and Live-birth Outcomes of Pregnancies following Assisted Reproductive Technology: A Retrospective Cohort Study. Sci Rep, 6:35141.

5d52b97b0e88256848daee84 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections