妊娠期间的母胎细胞转移被称为微嵌合物（Mc）。它在宿主中的持续存在被越来越多地研究其在免疫耐受、自身免疫、癌症和退行性疾病中的潜在作用。通过母亲携带的杂合转基因报告基因，可以追踪野生型（WT）幼仔中的母亲Mc。然而，因为小鼠的妊娠期是多胎的，具有与母亲相同报告基因的胎儿与阴性WT同胞之间的细胞交换，即同胞Mc（LMc），可能发生混淆，并与母源相混淆。我们在这里建议评估小鼠中LMc的贡献。为了避免Mc的母源混淆，携带报告基因（此处为人白细胞抗原DRB1*04（DR4+/-））的转基因雄性交配与WT雌性（DR4-/-）交配。通过HLA-DR4定量PCR，特异性地定量DR4+/- LMc，在15个DR4-/-胎儿（来自11个、9个和5个妊娠中）的主要器官，以及在两个胎儿中和四只成年DR4-/-小鼠的出生后进行定量。在胚胎阶段，同一个子宫角中具有一到两个附近的DR4+/-同胞的DR4-/-胎儿在其器官中的DR4-微嵌合物呈阳性的情况比没有附近DR4+/-同胞的DR4-/-胎儿多出近七倍（p = 0.01），且在定量上具有更多LMc（p = 0.009）。此外，LMc在出生后及成年时持续存在，并且存在个体间的异质性。本研究确定了根据胚胎期的位置和对小鼠母源Mc先前出版结果的不同解释，获得LMc的异质性。版权©2023 Giassi，Hemon，Martin，Roudier，Auger和Lambert。

Feto-maternal cell transfer during pregnancy is called microchimerism (Mc). Its persistence in respective hosts is increasingly studied as to its potential role in immune tolerance, autoimmunity, cancer, and degenerative diseases. Murine models with transgenic reporter genes, heterozygously carried by the mother, allow maternal Mc tracking in wild-type (WT) offspring. However, as gestation in mice is multi-embryonic, an exchange of cells between fetuses carrying the same reporter gene as their mother and negative WT littermate, named littermate Mc (LMc), can occur and be confounded with the maternal source. We propose here to evaluate LMc contribution in mice.To avoid the maternal confounding source of Mc, transgenic males, heterozygous for a reporter gene, here, the human leukocyte antigen DRB1*04 (DR4+/-), were crossed with WT females (DR4-/-). DR4+/- LMc was specifically quantified by HLA-DR4 quantitative PCR, i) in utero in main organs from 15 DR4-/- fetuses from three litters of 11, nine, and five; and ii) after birth in two litters of eight pups: in two DR4-/- stillborns and four DR4-/- adult mice.At embryonic stages, DR4-/- fetuses having one or two nearby DR4+/- littermates in the same uterine horn were almost seven times more frequently positive for DR4- microchimerism in their organs (p = 0.01) and had quantitatively more LMc (p = 0.009) than those without nearby DR4+/- littermates. Furthermore, LMc persists at birth and into adulthood with interindividual heterogeneity.This study identifies heterogeneity for LMc acquisition according to in utero position and different interpretation of previously published results on maternal Mc in mice.Copyright © 2023 Giassi, Hemon, Martin, Roudier, Auger and Lambert.