Examining Sex Differences in the Human Placental Transcriptome During the First Fetal Androgen Peak

Braun, Amy E.; Muench, Kristin; Robinson, Beatriz G; Wang, Angela Yee-Moon; Palmer, Theo; Winn, Virginia D.

doi:10.1007/s43032-020-00355-8

Cited by 25 publications

(38 citation statements)

References 107 publications

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“…These changes in placental transcript expression are likely brought on by sex-specific differences in the placental methylome, with some studies reporting an increase in the methylation of CpG sites in male placentae, relative to females [39,40]. Braun et al [41] identified that in female placentae, differentially expressed transcripts were enriched in extracellular matrix, mRNA splicing, and chromatin organisation, and subcellular associations included the extracellular matrix and the nucleus. To contrast this, and to support previous work, differentially expressed transcripts in male placentae were centered on oxidative phosphorylation and cellular catabolic processes, and subsequent gene ontology cellular compartment analysis reinforced associations with the mitochondrial compartment.…”

Section: From Blastocyst To Neonate: Ontogeny Of Sex-specific Intrauterine Growthmentioning

confidence: 99%

Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

Meakin

Cuffe

Darby

et al. 2021

IJMS

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It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific “evolutionary advantage” likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.

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Section: From Blastocyst To Neonate: Ontogeny Of Sex-specific Intrauterine Growthmentioning

confidence: 99%

Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

Meakin

Cuffe

Darby

et al. 2021

IJMS

View full text Add to dashboard Cite

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“…However, although increasing expression of LGALS13 , LGALS14 , and LGALS16 was observed during forskolin-induced syncytialization and differentiation of primary trophoblasts and BeWo cells in culture, only LGALS13 and LGALS14 were downregulated in preeclampsia with no significant changes of LGALS16 [ 12 ]. Remarkably, LGALS16 does not show sex-biased expression depending on the chromosomal sex of the fetus while LGALS13 and LGALS14 are notably elevated in fetal male placentas based on the chorionic villus transcriptome [ 59 ]. These aspects of galectin network regulation remain unclear in the context of placental disorders and development.…”

Section: Resultsmentioning

confidence: 99%

Expression, Regulation, and Functions of the Galectin-16 Gene in Human Cells and Tissues

Kaminker

Timoshenko

2021

Biomolecules

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Galectins comprise a family of soluble β-galactoside-binding proteins, which regulate a variety of key biological processes including cell growth, differentiation, survival, and death. This paper aims to address the current knowledge on the unique properties, regulation, and expression of the galectin-16 gene (LGALS16) in human cells and tissues. To date, there are limited studies on this galectin, with most focusing on its tissue specificity to the placenta. Here, we report the expression and 8-Br-cAMP-induced upregulation of LGALS16 in two placental cell lines (BeWo and JEG-3) in the context of trophoblastic differentiation. In addition, we provide the results of a bioinformatics search for LGALS16 using datasets available at GEO, Human Protein Atlas, and prediction tools for relevant transcription factors and miRNAs. Our findings indicate that LGALS16 is detected by microarrays in diverse human cells/tissues and alters expression in association with cancer, diabetes, and brain diseases. Molecular mechanisms of the transcriptional and post-transcriptional regulation of LGALS16 are also discussed based on the available bioinformatics resources.

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“…A search of publicly available GEO DataSets (https://www.ncbi.nlm.nih.gov/gds/) with the key words "human AND placenta" returned a total of 320 accessions that contained microarray or RNAseq data from Homo sapiens. Of these, however, only a few had performed tissue-specific sequencing or shared even superficial similarities with our study [23][24][25][26][27]. For example, Sitras et al [25] compared microarray-based transcriptomes of first trimester and term human placentas, but their analysis focused only on gestational age and did not investigate the effects of sex.…”

Section: Discussionmentioning

confidence: 99%

“…To investigate sexual dimorphism in the gene expression of human placentas, Braun et al [23] surveyed the human chorionic villus transcriptome from 11 to 16 GW for sexlinked signatures, with the goal of characterizing genes that are differentially expressed within the first window of increasing testis-derived androgen production in the male fetus. That study was similar to two others [24,27] that also focused on sex-based differences in the human placental transcriptome in the late first trimester, with minor differences in the cells or tissues examined.…”

Section: Discussionmentioning

confidence: 99%

Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen

Liu

Simasotchi

Vibert

et al. 2021

IJMS

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Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8–10 gestational weeks and 12–14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.

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Examining Sex Differences in the Human Placental Transcriptome During the First Fetal Androgen Peak

Cited by 25 publications

References 107 publications

Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

Let’s Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

Expression, Regulation, and Functions of the Galectin-16 Gene in Human Cells and Tissues

Age and Sex-Related Changes in Human First-Trimester Placenta Transcriptome and Insights into Adaptative Responses to Increased Oxygen

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