Michelle M Denomme1, Blair R McCallie1, Jason C Parks1, Keith Booher2, William B Schoolcraft3, Mandy G Katz-Jaffe4. 1. Fertility Labs of Colorado, Lone Tree, Colorado. 2. Zymo Research Corp., Irvine, California. 3. Colorado Center for Reproductive Medicine, Lone Tree, Colorado. 4. Fertility Labs of Colorado, Lone Tree, Colorado; Colorado Center for Reproductive Medicine, Lone Tree, Colorado. Electronic address: mkatz-jaffe@colocrm.com.
Abstract
OBJECTIVE: To evaluate the epigenetic consequence on the methylome and subsequent transcriptome in euploid blastocysts of male-factor (MF) infertility patients. DESIGN: Methylome and transcriptome analysis on individual oligoasthenoteratozoospermia (OAT [MF]) blastocysts. SETTING: Infertility clinic. PATIENT(S): Clinical data from 128 couples presenting with OAT (MF) and 118 maternal age-matched control (no MF) subjects undergoing infertility treatment from 2010 to 2014, along with 72 surplus cryopreserved blastocysts donated from 33 couples with their informed consents. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Methyl Maxi-Seq (Zymo Research) was used to determine genome-wide DNA methylation, and small cell number RNA-Seq was used to examine the global transcriptome. Validation experiments were performed with the use of pyrosequencing or quantitative real-time polymerase chain reaction. Statistical analysis used Student t test, analysis of variance in R, Fisher exact test, and pairwise fixed reallocation randomization test where appropriate, with significance at P<.05. RESULT(S): Clinical pregnancy rates were similar between OAT (MF) patients and control (no MF) subjects after euploid embryo transfer. However, the miscarriage rate for OAT (MF) patients was significantly higher (14.7% vs. 2.2%; P<.05). Methylome and transcriptome analyses of individual blastocysts revealed significant alterations in 1,111 CpG sites and 469 transcripts, respectively (P<.05). Pathway analysis elucidated genes involved in "regulation of cellular metabolic process" as universally affected. Validation of the genome-wide approaches was performed for SBF1 and SLC6A9 (P<.05). CONCLUSION(S): Methylation and transcription aberrations in individual OAT (MF) blastocysts illustrate an epigenetic consequence of MF infertility on embryogenesis, significantly altering key developmental genes and affecting embryonic competence. This epigenetic dysregulation provides an explanation for the reduced reproductive potential in OAT (MF) patients despite euploid blastocyst transfers.
OBJECTIVE: To evaluate the epigenetic consequence on the methylome and subsequent transcriptome in euploid blastocysts of male-factor (MF) infertilitypatients. DESIGN: Methylome and transcriptome analysis on individual oligoasthenoteratozoospermia (OAT [MF]) blastocysts. SETTING:Infertility clinic. PATIENT(S): Clinical data from 128 couples presenting with OAT (MF) and 118 maternal age-matched control (no MF) subjects undergoing infertility treatment from 2010 to 2014, along with 72 surplus cryopreserved blastocysts donated from 33 couples with their informed consents. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Methyl Maxi-Seq (Zymo Research) was used to determine genome-wide DNA methylation, and small cell number RNA-Seq was used to examine the global transcriptome. Validation experiments were performed with the use of pyrosequencing or quantitative real-time polymerase chain reaction. Statistical analysis used Student t test, analysis of variance in R, Fisher exact test, and pairwise fixed reallocation randomization test where appropriate, with significance at P<.05. RESULT(S): Clinical pregnancy rates were similar between OAT (MF) patients and control (no MF) subjects after euploid embryo transfer. However, the miscarriage rate for OAT (MF) patients was significantly higher (14.7% vs. 2.2%; P<.05). Methylome and transcriptome analyses of individual blastocysts revealed significant alterations in 1,111 CpG sites and 469 transcripts, respectively (P<.05). Pathway analysis elucidated genes involved in "regulation of cellular metabolic process" as universally affected. Validation of the genome-wide approaches was performed for SBF1 and SLC6A9 (P<.05). CONCLUSION(S): Methylation and transcription aberrations in individual OAT (MF) blastocysts illustrate an epigenetic consequence of MF infertility on embryogenesis, significantly altering key developmental genes and affecting embryonic competence. This epigenetic dysregulation provides an explanation for the reduced reproductive potential in OAT (MF) patients despite euploid blastocyst transfers.
Authors: Blair R McCallie; Mary Haywood; Michelle M Denomme; Rachel Makloski; Jason C Parks; Darren K Griffin; William B Schoolcraft; Mandy G Katz-Jaffe Journal: J Assist Reprod Genet Date: 2021-03-30 Impact factor: 3.357
Authors: Federica Barbagallo; Aldo E Calogero; Rosita A Condorelli; Ashraf Farrag; Emmanuele A Jannini; Sandro La Vignera; Claudio Manna Journal: J Clin Med Date: 2021-09-26 Impact factor: 4.241
Authors: Michelle M Denomme; Jason C Parks; Blair R McCallie; Nathan I McCubbin; William B Schoolcraft; Mandy G Katz-Jaffe Journal: PLoS One Date: 2020-03-06 Impact factor: 3.240