Placental Sex Differences: Q&A with Amy Inkster

Amy Inkster is the 2019 winner of the Biology of Sex Differences Best Poster Prize at the recent OSSD meeting in May. This Q&A provides an overview of her research into sex differences in placentas and how this can impact the pregnancy and postnatal outcomes.

At the May meeting of the Organization for the Study of Sex Differences (OSSD), Amy Inkster’s poster titled “Sex-specific patterns of autosomal DNA methylation in the human placenta” was selected as the winner of the性别差异的生物学Best Poster Prize.

Learn more about Amy, the sex of placentas, and the importance of considering sex differences in pregnancy research in this Q&A with her.

是什么促使您在怀孕研究中考虑性差异?为什么这对您很重要?

When we study pregnancy complications, too often sex differences are not considered, and are rarely investigated directly. During pregnancy, the sex of a developing baby (either male or female based on chromosome complement) impacts both mother and baby’s risk for developing certain pregnancy complications. For example, male babies are far more likely to be born preterm, which puts them at increased risk for postnatal inflammation and infection. I’m interested in going back to basics to understand these sex differences on a molecular level, and how they relate to sex-specific pregnancy outcomes.

Briefly describe your primary area of interest and research. Which questions are you and your lab lab looking to answer?

My lab, under the supervision of温迪·罗宾逊博士, studies genetic and epigenetic aspects of human reproduction and development, with a large focus on the human placenta. The placenta is an absolutely essential organ that develops during pregnancy to mediate fetal growth and development throughout gestation – without the placenta, none of us would be here. Many students in my lab study specific complications of pregnancy, such aspreeclampsia绒毛膜炎,并研究在这些条件下胎盘的分子特征如何改变。

由温迪·P·罗宾逊(Wendy P Robinson)领导的卑诗省儿童医院研究所的罗宾逊实验室(右边是第一人称)。艾米·墨器(Amy Inkster)出现在左侧第二(从左到右)。

性别差异与怀孕有关。毕竟,怀孕是只有生物女性经历的现象。但是实际上,性行为在妊娠期间非常重要,当人们考虑发育中的婴儿的性别时,就开始发挥作用。胎盘起源于与婴儿的同一细胞池,因此婴儿和胎盘都具有生物学性。雄性胎盘,就像雄性婴儿一样,有Y染色体。

My research focuses on thoroughly characterizing sex differences in the placentas of normal babies delivered at term, by epigenetic and gene expression profiling. Even during healthy pregnancies, male and female babies develop differently, and their placentas exhibit sex-specific structure and function. When we understand the baseline differences in male and female placentas, we can apply that knowledge to investigate why certain pregnancy complications tend to affect the sexes disproportionately. Hopefully one day, this work will contribute to advancing diagnosis and treatment of these conditions, as it is possible that we could achieve better outcomes by considering the biological sex of the developing baby in deciding clinical interventions.

What challenges have you (and likely other researchers) faced when trying to ensure sex differences are taken into account in your research design?

我最近想到的是,大多数具有性别差异的生物学特征不是性二态性的。换句话说,重要的是要区分性二态性和性别特异性。性二态性是指存在两种不同形式的特质形式,例如人类染色体补体(女性是XX,男性是XY,尽管有例外),性别特异性是指某种特征的特征,这些特征表现出性别差异,也指重叠(例如,雄性胎儿通常在妊娠中期产生高浓度的睾丸激素,但在女性中也会产生睾丸激素,在某些情况下可以在高水平上存在)。我们在该项目中考虑的特征,例如男性早产的风险增加,是​​性别特定的。当在许多情况下实际讨论的是性别特异性时,经常使用“性二态性”一词。

This image shows the sites found to be differentially methylated by sex on autosomal DNA. Note that males and females aren’t separated into discrete groups, but spread across a continuum.

Have you had any surprising or unexpected results in your research? What were they and how have they impacted your understanding of pregnancy/placental changes?

我认为有趣的是,我们在常染色体上看到表观遗传概况的强大性别差异。尽管X和Y染色体是性别差异的第一个逻辑场所,但这项研究表明,整个基因组中性别存在表观遗传学差异,尽管它们很小,但它们在独立的数据集中进行了验证,因此它们是强大的。

What future directions do you hope to be able to explore in your research and why?

将来,我想调查我们在分子特征中看到的性别差异可能对胎盘功能和胎儿健康意味着什么。进一步研究哪些基因在健康的雄性和雌性胎盘之间差异表达,并将这些差异与我们在妊娠并发症中看到的差异与性偏见进行比较。在这些情况下,是否会放大正常模式以增加男性女性差异,或者潜在地增加新的性别特异性模式?

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