Fetal sex differences in placental LCPUFA ether and plasmalogen phosphatidylethanolamine and phosphatidylcholine contents in pregnancies complicated by obesity.
Fetal sex differences in placental LCPUFA ether and plasmalogen phosphatidylethanolamine and phosphatidylcholine contents in pregnancies complicated by obesity.
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DOI：
10.1186/s13293-023-00548-1
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发表时间：
2023-09-28
影响因子：
7.9
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中科院分区：
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我们之前曾报道，母亲肥胖会降低胎盘输送溶血磷脂酰胆碱-二十二碳六烯酸 (LPC-DHA) 的能力，这是将 DHA (omega 3) 转移到胎儿大脑的首选形式，但仅限于男性胎儿。磷脂酰乙醇胺 (PE) 和磷脂酰胆碱 (PC) 在 sn-2 位上具有与主要不饱和和单不饱和脂肪酸以及 DHA 或花生四烯酸（ARA、omega 6）连接的 sn-1 酯、醚或乙烯基醚（缩醛磷脂）。胎盘中乙醚和缩醛磷脂 PC 和 PE 的代谢是否会影响向胎儿的转移尚不清楚。我们假设，在妊娠并发肥胖的情况下，母胎单位中含有 DHA 和 ARA 的乙醚和缩醛磷脂 PC 和 PE 会减少，并且这些差异取决于胎儿性别。在来自肥胖女性（11 名女性/5 名男性婴儿）和正常体重女性（9 名女性/7 名男性婴儿）的母体、脐带血浆和胎盘中，所有含有 DHA 和 ARA 的 PC 和 PE 物种均通过 LC-MS/MS 进行了分析。通过免疫印迹测定参与磷脂合成的酶的胎盘蛋白表达。对对照组与肥胖组之间的所有变量进行比较，并按胎儿性别分开，在每个样本中使用本杰明-霍赫伯格错误发现率调整来解释多重测试。在肥胖母亲的男性胎盘中，含有 DHA 和 ARA 的酯 PC 水平显着降低了 60-92%，而在女性胎盘中，含有 DHA 和 ARA 的乙醚和缩醛磷脂 PE 水平则降低了 51-84%。 PLA2G4C 丰度在男性胎盘中较低，LPCAT4 丰度仅在肥胖女性中较低。在肥胖母亲的男性胎儿中，脐带中酯、醚、缩醛磷脂 PC 和 PE 与 DHA 的水平降低了 43-61%，但女性胎儿则没有。我们发现胎盘 PE 和 PC 中含有 DHA 的酯、醚和缩醛磷脂 PE 和 PC 对母体肥胖的胎儿性别影响，这似乎反映了女性胎盘在母体肥胖中适应维持最佳胎儿 DHA 转移的能力。在线版本包含可在 10.1186/s13293-023-00548-1 获取的补充材料。乙醚和缩醛磷脂磷脂酰胆碱 (PC) 和磷脂酰乙醇胺 (PE) 被认为是 DHA 储存库，并且它们在胎盘中的代谢以及 DHA 向胎儿的转移是否会因肥胖而改变尚未被探索，尤其是在胎儿性别方面。我们发现，在肥胖症中，(1)妊娠男性胎儿会减少胎盘中含有DHA和ARA的酯PC，但不会减少缩醛磷脂PC种类，并且胎儿脐带循环中含有DHA的酯、醚和缩醛磷脂PC和PE的水平降低；(2)妊娠女性胎儿会减少胎盘中含有DHA和ARA的醚和缩醛磷脂PE，并维持胎儿循环中含有DHA的酯、醚和缩醛磷脂PC和PE的水平。男性和女性都有补偿机制，试图在肥胖时维持 DHA 种类的充足供应，特别是对于大脑发育而言，然而，男性胎盘的适应未能将胎儿水平维持在正常体重妊娠时的水平。在线版本包含可在 10.1186/s13293-023-00548-1 获取的补充材料。二十二碳六烯酸 (DHA) 是一种对胎儿大脑发育至关重要的 omega 3 长链多不饱和脂肪酸 (LCPUFA)。我们最近报道称，母亲肥胖会降低胎盘输送溶血磷脂酰胆碱-DHA (LPC-DHA) 的能力，LPC-DHA 是 DHA 转移至胎儿大脑的首选形式，但仅限于男性胎儿。其他重要的脂质、缩醛磷脂磷脂酰胆碱 (PC) 和磷脂酰乙醇胺 (PE) 被认为是 DHA 储存库，但其在母胎单位中的作用很大程度上尚未被探索。我们检查了母体和胎儿循环以及胎盘组织中的这些脂质种类，以揭示醚和缩醛磷脂脂质在调节胎盘输送这些重要营养素的过程中的潜在新作用，这些重要营养素在怀孕期间并发肥胖，具体取决于胎儿性别。 我们首次证明，肥胖母亲的女性胎儿会减少含有 DHA 和花生四烯酸（ARA、omega 6）的胎盘醚和缩醛磷脂 PE，并表现出较高的胎儿-胎盘适应性和胎盘储备能力，可以维持 PC-LCPUFA 的合成以及这些关键物质向胎儿的转移，以保护大脑发育。我们的研究还表明，针对母亲肥胖，男性胎儿会减少含有 DHA 和 ARA 的胎盘酯 PC 种类，并减少胎儿循环中 DHA 和 ARA 的乙醚和缩醛磷脂 PE 储存。 我们的研究结果支持含有 DHA 的胎盘酯、醚和缩醛磷脂 PE 和 PC 对母体肥胖的胎儿性别影响，这似乎反映了女性胎盘在母体肥胖中适应维持最佳胎儿 DHA 转移的能力。在线版本包含可在 10.1186/s13293-023-00548-1 获取的补充材料。
We have previously reported that maternal obesity reduces placental transport capacity for lysophosphatidylcholine-docosahexaenoic acid (LPC-DHA), a preferred form for transfer of DHA (omega 3) to the fetal brain, but only in male fetuses. Phosphatidylethanolamine (PE) and phosphatidylcholine (PC), have either sn-1 ester, ether or vinyl ether (plasmalogen) linkages to primarily unsaturated and monounsaturated fatty acids and DHA or arachidonic acid (ARA, omega 6) in the sn-2 position. Whether ether and plasmalogen PC and PE metabolism in placenta impacts transfer to the fetus is unexplored. We hypothesized that ether and plasmalogen PC and PE containing DHA and ARA are reduced in maternal–fetal unit in pregnancies complicated by obesity and these differences are dependent on fetal sex. In maternal, umbilical cord plasma and placentas from obese women (11 female/5 male infants) and normal weight women (9 female/7 male infants), all PC and PE species containing DHA and ARA were analyzed by LC–MS/MS. Placental protein expression of enzymes involved in phospholipid synthesis, were determined by immunoblotting. All variables were compared between control vs obese groups and separated by fetal sex, in each sample using the Benjamini–Hochberg false discovery rate adjustment to account for multiple testing. Levels of ester PC containing DHA and ARA were profoundly reduced by 60–92% in male placentas of obese mothers, while levels of ether and plasmalogen PE containing DHA and ARA were decreased by 51–84% in female placentas. PLA2G4C abundance was lower in male placentas and LPCAT4 abundance was lower solely in females in obesity. In umbilical cord, levels of ester, ether and plasmalogen PC and PE with DHA were reduced by 43–61% in male, but not female, fetuses of obese mothers. We found a fetal sex effect in placental PE and PC ester, ether and plasmalogen PE and PC containing DHA in response to maternal obesity which appears to reflect an ability of female placentas to adapt to maintain optimal fetal DHA transfer in maternal obesity. The online version contains supplementary material available at 10.1186/s13293-023-00548-1. Ether and plasmalogen phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are considered DHA reservoirs and whether their metabolism in placenta and DHA transfer to the fetus are altered in obesity is unexplored, especially regarding the fetal sex. We found that in obesity, (1) pregnancies with male fetuses decrease ester PC with DHA and ARA in placentas but not plasmalogen PC species and the levels of ester, ether and plasmalogen PC and PE with DHA is decreased in fetal umbilical circulation, and (2) pregnancies with female fetuses decrease ether and plasmalogen PE with DHA and ARA in placentas and maintain the levels of ester, ether and plasmalogen PC and PE with DHA in fetal circulation. Both males and females have compensatory mechanisms that attempt to maintain an adequate supply of DHA species, particularly for brain development, in obesity, however, the male placental adaptation failed to maintain fetal levels to those found in normal weight pregnancies. The online version contains supplementary material available at 10.1186/s13293-023-00548-1. Docosahexaenoic acid (DHA) is a critical omega 3 long chain polyunsaturated fatty acid (LCPUFA) for fetal brain development. We have recently reported that maternal obesity reduces placental transport capacity for LysophosPhatidylCholine-DHA (LPC-DHA), a preferred form for transfer of DHA to the fetal brain, but only in male fetuses. Other important lipids, the plasmalogen phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are considered DHA reservoirs, but its roles in the maternal–fetal unit are largely unexplored. We examined these lipid species in maternal and fetal circulation and in placental tissue to uncover potential novel roles for ether and plasmalogen lipids in the regulation of placenta delivery of these vital nutrients in pregnancies complicated by obesity depending of fetal sex. We demonstrated for the first time, that female fetuses of obese mothers decrease placental ether and plasmalogen PE containing DHA and arachidonic acid (ARA, omega 6), and show a high fetal–placental adaptability and placental reserve capacity that can maintain the PC-LCPUFA synthesis and the transfer of these crucial species to the fetus to preserve brain development. Our study also demonstrated that male fetuses, in response to maternal obesity, reduce the placental ester PC species containing DHA and ARA and reduce the ether and plasmalogen PE reservoir of DHA and ARA in fetal circulation. Our findings support a fetal sex effect in placental ester, ether and plasmalogen PE and PC containing DHA in response to maternal obesity which appears to reflect an ability of female placentas to adapt to maintain optimal fetal DHA transfer in maternal obesity. The online version contains supplementary material available at 10.1186/s13293-023-00548-1.
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DOI：
10.1042/cs20190266
发表时间：
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影响因子：
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影响因子：
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DOI：
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发表时间：
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期刊：
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DOI：
10.1016/j.bbamcr.2008.05.018
发表时间：
2008-10-01
影响因子：
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