Decreased fecundity and sperm DNA methylation patterns

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Decreased fecundity and sperm DNA methylation patterns Timothy G. Jenkins, Ph.D., Kenneth I. Aston, Ph.D., Tyson D. Meyer, B.S., James M. Hotaling, M.D., M.S., Monis B. Shamsi, Ph.D., Erica B. Johnstone, M.D., Kyley J. Cox, M.P.H., Joseph B. Stanford, M.D., M.S.P.H., Christina A. Porucznik, Ph.D., M.S.P.H., Douglas T. Carrell, Ph.D. Fertility and Sterility Volume 105, Issue 1, Pages 51-57.e3 (January 2016) DOI: 10.1016/j.fertnstert.2015.09.013 Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Figure 1 The most significant regional methylation alteration associated with pregnancy is shown in the Integrated Genome Browser at HSPA1L (A). Average absolute methylation change (B) across all CpGs analyzed and (C) at the most highly affected CpGs can be seen. Hypomethylation at this site is associated with our group of couples who did not achieve a pregnancy with a transformed corrected false discovery rate of 105.5. Fertility and Sterility 2016 105, 51-57.e3DOI: (10.1016/j.fertnstert.2015.09.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Figure 2 We analyzed the frequency of two methylation profiles at heat shock protein (HSP) loci of interest. We calculated the frequency of samples that displayed (A) strong hypomethylation (β-value <0.1), and (B) intermediate methylation (β-value between 0.2 and 0.8) at two sites of interest, HSPA1L and HSPA1B, in four distinct time to pregnancy categories: 0–4 months of attempted conception, 4–8 months of attempted conception, 8–14 months of attempted conception, and no pregnancy achieved during within the study timeframe. (C) We additionally performed linear regression analysis on fraction methylation values at HSPA1L and HSPA1B and identified a strong correlation between the two values within individuals (P<.0001). Fertility and Sterility 2016 105, 51-57.e3DOI: (10.1016/j.fertnstert.2015.09.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 General methylation levels were analyzed by global analysis. (A) An analysis of coefficient of variance revealed no statistically significant difference between the pregnant and not pregnant groups (P=.5198). Similarly, no statistically significant difference was identified in global methylation at (B) all cytosines (P=.7608) or (C) only cytosines outside of CpG context (non-CpG methyalion; P=.4331). P<.05 was considered statistically significant. Fertility and Sterility 2016 105, 51-57.e3DOI: (10.1016/j.fertnstert.2015.09.013) Copyright © 2016 American Society for Reproductive Medicine Terms and Conditions