Examining Fetal Sex-Specific Placental DNA Methylation Intensities and Variability Post <i>In Vitro</i> Fertilization
Bibliographic record
Abstract
Abstract Infertility impacts up to 17.5% of reproductive-aged couples worldwide. To aid in conception, many couples turn to assisted reproductive technology, such as in vitro fertilization (IVF). IVF can introduce both physical and environmental stressors that may alter DNA methylation regulation, an important and dynamic process during early fetal development. This meta-analysis aims to assess the differences in the placental DNA methylome between spontaneous and IVF pregnancies. We identified three studies from NCBI GEO that measured DNA methylation with an Illumina Infinium Microarray in post-delivery placental tissue from both IVF and spontaneous pregnancies with a total of 575 samples for analysis (n = 96 IVF, n = 479 spontaneous). While there were no significant or differentially methylated CpGs in mixed or female stratified populations, we identified 9 CpGs that reached statistical significance (FDR <0.05) between IVF (n = 56) and spontaneous (n = 238) placentae. 7 autosomal CpGs and 1 X chromosome CpG was hypermethylated and 2 autosomal CpGs were hypomethylated in the IVF placentae compared to spontaneous. Autosomal CpGs closest to LIPJ , EEF1A2 , and FBRSL1 also met our criteria to be classified as biologically differentially methylated CpGs (FDR <0.05, |Δ β |>0.05). When analyzing variability differences in Δ β values between IVF females, IVF males, spontaneous females and spontaneous males, we found a significant shift to greater variability in the both IVF males and females compared to spontaneous (p <2.2e-16, p <2.2e-16). Trends of variability were further analyzed in the biologically differentially methylated autosomal CpGs near LIPJ EEF1A2 , and FBRSL1 , and while these regions were statistically significant in males, the female Δ β s and ΔCoVs followed a similar trend that differed in magnitude. In males and females there was a statistically significant difference in proportions of endothelial cells, hofbauer cells, stromal cells and syncytiotrophoblasts between spontaneous and in vitro Fertilization (IVF) populations. We also observed significant differences between sex within reproduction type in syncytiotrophoblasts and trophoblasts. The results of this study are critical to further understand the impact of IVF on tissue epigenetics which may help to investigate the connections between IVF and negative pregnancy outcomes. Additionally, our study supports sex specific differences in placental DNA methylation and cell composition should be considered as factors for future placental DNA methylation analyses.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.007 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.003 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".