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Epigenetic consequences of hormonal interactions between opposite-sex twin fetuses.

ABSTRACT: Previous studies reported inconsistent evidence about some phenotypic traits of females in human opposite-sex twins (opposite-sex females [OSF]) being distinct from females in same-sex twins (SSF). Comparatively, less evidence showed significant differences between males in OS twins (opposite-sex males [OSM]) and males in same-sex twins (SSM). The twin testosterone transfer hypothesis suggests that prenatal exposure of testosterone in utero may be a possible explanation for the differential traits in OSF; however, the underlying mechanism is unknown. Here, we investigated the potential epigenetic effects of hormone interactions and their correlation to the observed phenotypic traits. In the study, DNA methylomic data from 54 newborn twins and histone modification data (H3K4me3, H3K4me1, H3K27me3, and H3K27ac) from 14 newborn twins, including same-sex females (SSF), OS twins, and same-sex males (SSM) were generated. We found that OSF were clearly distinguishable from SSF by DNA methylome, while OSM were distinguishable from SSM by H3K4me1 and H3K4me3. To be more specific, compared to SSF, OSF showed a stronger correlation to males (OSM and SSM) in genome-wide DNA methylation. Further, the DNA methylomic differences between OSF and SSF were linked to the process involving cognitive functions and nervous system regulation. The differential H3K4me3 between OSM and SSM was linked to immune responses. These findings provide epigenetic evidence for the twin testosterone transfer hypothesis and offer novel insights on how prenatal hormone exposure in utero may be linked to the reported differential traits of OS twins.

SUBMITTER: Kong S

PROVIDER: S-EPMC7717068 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Epigenetic consequences of hormonal interactions between opposite-sex twin fetuses.

Kong Siming S Peng Yong Y Chen Wei W Ma Xinyi X Wei Yuan Y Zhao Yangyu Y Li Rong R Qiao Jie J Yan Liying L

Clinical and translational medicine 20201201 8

Previous studies reported inconsistent evidence about some phenotypic traits of females in human opposite-sex twins (opposite-sex females [OSF]) being distinct from females in same-sex twins (SSF). Comparatively, less evidence showed significant differences between males in OS twins (opposite-sex males [OSM]) and males in same-sex twins (SSM). The twin testosterone transfer hypothesis suggests that prenatal exposure of testosterone in utero may be a possible explanation for the differential trai ...[more]

PMID: 33377650

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Project description:BACKGROUND:Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. It results from disproportionate blood supply to each fetus caused by abnormal vascular anastomosis within the placenta. Amniotic fluid (AF) is an indicator reflecting the various conditions of the fetus, and an imbalance in AF volume is essential for the antenatal diagnosis of TTTS by ultrasound. In this study, two different mass spectrometry quantitative approaches were performed to identify differentially expressed proteins (DEPs) within matched pairs of AF samples. METHODS:We characterized the AF proteome in pooled AF samples collected from donor and recipient twin pairs (n = 5 each) with TTTS by a global proteomics profiling approach and then preformed the statistical analysis to determine the DEPs between the two groups. Next, we carried out a targeted proteomic approach (multiple reaction monitoring) with DEPs to achieve high-confident TTTS-associated AF proteins. RESULTS:A total of 103 AF proteins that were significantly altered in their abundances between donor and recipient fetuses. The majority of upregulated proteins identified in the recipient twins (including carbonic anhydrase 1, fibrinogen alpha chain, aminopeptidase N, alpha-fetoprotein, fibrinogen gamma chain, and basement membrane-specific heparan sulfate proteoglycan core protein) have been associated with cardiac or dermatologic disease, which is often seen in recipient twins as a result of volume overload. In contrast, proteins significantly upregulated in AF collected from donor twins (including IgGFc-binding protein, apolipoprotein C-I, complement C1q subcomponent subunit B, apolipoprotein C-III, apolipoprotein A-II, decorin, alpha-2-macroglobulin, apolipoprotein A-I, and fibronectin) were those previously shown to be associated with inflammation, ischemic cardiovascular complications or renal disease. CONCLUSION:In this study, we identified proteomic biomarkers in AF collected from donor and recipient twins in pregnancies complicated by TTTS that appear to reflect underlying functional and pathophysiological challenges faced by each of the fetuses.

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Epigenetic consequences of hormonal interactions between opposite-sex twin fetuses.

Publications

Epigenetic consequences of hormonal interactions between opposite-sex twin fetuses.

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