Maternal smoking affects human fetal X-inactivation

IF 2.8 4区医学 Q2 REPRODUCTIVE BIOLOGY

Reproductive toxicology Pub Date : 2025-07-22 DOI:10.1016/j.reprotox.2025.109010

Sanam Zeib Khan , Linn Salto Mamsen , Erik Ernst , Esben Budtz-Jørgensen , Claus Yding Andersen , Niels Tommerup

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引用次数: 0

Abstract

Females inactivate one of their two X-chromosomes in each cell before implantation, at a time where any factor that affect the number of these primordial cells may lead to deviation from the usual random choice. Thus, non-random (skewed) X-inactivation may occur due to early stochastic effects in the limited primordial pool size. The primodial pool size can be calculated from the variance of the ratio between the unmethylated and methylated CAG-repeats within exon 1 of the androgen receptor gene (AR) corresponding to the active and inactive X-chromosome (X-inactivation (XI)-ratio), respectively. Since maternal smoking during pregnancy is associated with a general growth inhibition and a reduced number of fetal gonadal cells, we have tested the XI-ratios in tissues obtained from fetuses of smoking (n = 8) and non-smoking (n = 10) mothers in connection with legal termination of the pregnancy. A tighter distribution of XI-ratios was seen in tissues from fetuses in the smoking group. Combined with more skewed X-inactivation (>=80 %) and a higher mean XI-ratio in the fetal samples from pregnancies of non-smoking mothers, this support a larger pool of primordial cells in fetuses exposed to smoking, suggesting that smoking during pregnancy delays fetal X inactivation.

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母亲吸烟影响人类胎儿的x -失活。

在植入之前，雌性在每个细胞中使两条x染色体中的一条失活，在这个时候，任何影响这些原始细胞数量的因素都可能导致偏离通常的随机选择。因此，在有限的原始池大小中，由于早期的随机效应，可能会发生非随机（倾斜）x失活。原始池大小可以通过雄激素受体基因（AR）外显子1内未甲基化和甲基化的cag -重复序列之间的比值（x -失活(XI)-比值）的方差来计算。由于母亲在怀孕期间吸烟与生长抑制和胎儿性腺细胞数量减少有关，我们测试了从吸烟（n=8）和不吸烟（n=10）母亲的胎儿组织中获得的xi -比率与合法终止妊娠的关系。吸烟组胎儿组织中的xi -比值分布更为紧密。结合非吸烟母亲的胎儿样本中X-失活更偏（>=80%）和更高的平均X-比值，这支持暴露于吸烟的胎儿中有更大的原始细胞池，表明怀孕期间吸烟延迟了胎儿X-失活。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.