Campesi Ilaria, Capobianco Giampiero, Cano Antonella, Lodde Valeria, Cruciani Sara, Maioli Margherita, Sotgiu Giovanni, Idda Maria Laura, Puci Mariangela Valentina, Ruoppolo Margherita, Costanzo Michele, Caterino Marianna, Cambosu Francesca, Montella Andrea, Franconi Flavia
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy.
Laboratory of Sex-Gender Medicine, National Institute of Biostructures and Biosystems, 07100 Sassari, Italy.
Biomedicines. 2023 Oct 18;11(10):2830. doi: 10.3390/biomedicines11102830.
Amniotic fluid is essential for fetus wellbeing and is used to monitor pregnancy and predict fetal outcomes. Sex affects health and medicine from the beginning of life, but knowledge of its influence on cell-depleted amniotic fluid (AF) and amniotic fluid cells (AFCs) is still neglected. We evaluated sex-related differences in AF and in AFCs to extend personalized medicine to prenatal life. AFCs and AF were obtained from healthy Caucasian pregnant women who underwent amniocentesis at the 16th-18th week of gestation for advanced maternal age. In the AF, inflammation biomarkers (TNFα, IL6, IL8, and IL4), malondialdehyde, nitrites, amino acids, and acylcarnitines were measured. Estrogen receptors and cell fate (autophagy, apoptosis, senescence) were measured in AFCs. TNFα, IL8, and IL4 were higher in female AF, whereas IL6, nitrites, and MDA were similar. Valine was higher in male AF, whereas several acylcarnitines were sexually different, suggesting a mitochondrial involvement in establishing sex differences. Female AFCs displayed higher expression of ERα protein and a higher ERα/ERβ ratio. The ratio of LC3II/I, an index of autophagy, was higher in female AFCs, while gene was similar in both sexes. No significant sex differences were found in the expression of the lysosomal protein LAMP1, while p62 was higher in male AFCs. gene was upregulated in male AFCs, while gene was upregulated in female ones. Finally, caspase 9 activity and senescence linked to telomeres were higher in female AFCs, while caspase 3 and β-galactosidase activities were similar. This study supports the idea that sex differences start very early in prenatal life and influence specific parameters, suggesting that it may be relevant to appreciate sex differences to cover knowledge gaps. This might lead to improving the diagnosis of risk prediction for pregnancy complications and achieving a more satisfactory monitoring of fetus health, even preventing future diseases in adulthood.
羊水对胎儿的健康至关重要，可用于监测孕期情况并预测胎儿结局。性别从生命伊始就会影响健康和医学，但关于其对细胞耗竭的羊水（AF）和羊水细胞（AFCs）的影响仍未得到充分关注。我们评估了AF和AFCs中的性别相关差异，以将个性化医疗扩展到产前阶段。AFCs和AF取自因高龄产妇在妊娠第16至18周接受羊膜穿刺术的健康白种孕妇。在羊水中，检测了炎症生物标志物（TNFα、IL6、IL8和IL4）、丙二醛、亚硝酸盐、氨基酸和酰基肉碱。在AFCs中检测了雌激素受体和细胞命运（自噬、凋亡、衰老）。女性羊水中TNFα、IL8和IL4水平较高，而IL6、亚硝酸盐和丙二醛水平相似。男性羊水中缬氨酸水平较高，而几种酰基肉碱存在性别差异，提示线粒体参与了性别差异的形成。女性AFCs显示出较高的ERα蛋白表达和较高的ERα/ERβ比值。自噬指标LC3II/I的比值在女性AFCs中较高，而相关基因在两性中相似。溶酶体蛋白LAMP1的表达未发现明显性别差异，而p62在男性AFCs中较高。相关基因在男性AFCs中上调，而在女性中上调。最后，女性AFCs中与端粒相关的半胱天冬酶9活性和衰老水平较高，而半胱天冬酶3和β-半乳糖苷酶活性相似。这项研究支持了性别差异在产前阶段很早就开始并影响特定参数的观点，表明认识性别差异对于填补知识空白可能具有重要意义。这可能有助于改善妊娠并发症风险预测的诊断，实现对胎儿健康更令人满意的监测，甚至预防成年后的未来疾病。
