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Physiology and Biochemistry

Associations of fertility parameters with fatty acids and DNA methylation in Mexican women undergoing in vitro fertilization

Abstract

Background

Fatty acids (FA) likely affect human fertility at multiple levels, as deviations from physiological FA profiles are obesogenic, and FA can modify DNA methylation (DNAm). Yet, the interplay of follicular fluid (FF) and serum FA with BMI and percentage body fat (PBF) in human fertility is not completely understood. Also, associations of DNAm with fertility are largely unexplored.

Methods

Reproductive parameters ranging from retrieved oocyte number to infant birth weight, were recorded in Mexican women undergoing in vitro fertilization (n = 88). Multiple regression analysis sought BMI-adjusted and age-adjusted associations. Receiver operating characteristic analysis tested for discrimination between outcomes.

Results

Associations of FF and serum FA were markedly distinct. While various FF FA (C16:1, C18:0, C20:2, C20:3, arachidonic acid) were significantly and inversely associated only with retrieved oocyte number, selected serum FA were associated with a broad range of pre-fertilization and post-fertilization parameters. Associations of BMI and FF FA were complex, as arachidonic acid was inversely associated with both BMI and retrieved oocyte number, while oleic acid (OA) was directly associated with BMI and PBF. Ultrasound-assessed clinical pregnancy outcome (CP) was directly associated with serum OA but inversely with its trans isomer elaidic acid (EA) and with BMI. Compounded BMI, serum EA and OA discriminated CP well (AUC = 0.74). Whole blood DNA methylation was significantly associated with and a moderate predictor (AUC = 0.66) of percent fertilized oocytes.

Conclusions

Overall FF FA pool composition rather than FA identity may impact oocyte production and cellular memory of FF FA is lost as the oocyte exits the follicular environment. The contrasting associations of BMI, FF OA and arachidonic acid suggest that the control of oocyte homeostasis by FF FA is uncoupled from BMI. Further studies are warranted to assess the potential of compounding BMI with serum EA and OA to predict CP.

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Fig. 1: Circos visualization of significant associations in FF and serum.
Fig. 2: Receiver operating characteristic (ROC) curve of BMI-, EA-, and OA-based score (BEO score) as predictor of clinical pregnancy outcome.

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Acknowledgements

Work supported by the Mexican National Council for Research and Technology. (CONACyT) “Ciencia Básica” grant no. A1-S-51654 to GL. PZ-S was supported by a CONACyT Postgraduate Student fellowship.

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Contributions

PZ-S obtained most of the biological samples and performed most of the experimental work, and created the database. CG-O, PC-V, and SM-G recruited the subjects and assisted the obtention of biological samples. JM-T and ER-C performed FA analysis. GL and SZ designed the study, interpreted the data and prepared the first draft of the manuscript. SZ performed most of the statistics. AMG-G supervised the recruitment of subjects and the generation of biological samples. All authors read and provided feedback to the manuscript content.

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Correspondence to Antonio M. Gutiérrez-Gutiérrez, Gertrud Lund or Silvio Zaina.

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Zúñiga-Sánchez, P., González-Ortega, C., Cancino-Villarreal, P. et al. Associations of fertility parameters with fatty acids and DNA methylation in Mexican women undergoing in vitro fertilization. Int J Obes 47, 75–82 (2023). https://doi.org/10.1038/s41366-022-01243-8

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