Department of Pathobiology and Population Sciences, Royal Veterinary College, London AL9 7TA, UK.
Department of Biomedical Sciences, Baker Institute for Animal Health, Cornell University, Ithaca, NY 14853.
Proc Natl Acad Sci U S A. 2024 Aug 13;121(33):e2405636121. doi: 10.1073/pnas.2405636121. Epub 2024 Aug 5.
Chromosomal abnormalities are a common cause of human miscarriage but rarely reported in any other species. As a result, there are currently inadequate animal models available to study this condition. Horses present one potential model since mares receive intense gynecological care. This allowed us to investigate the prevalence of chromosomal copy number aberrations in 256 products of conception (POC) in a naturally occurring model of pregnancy loss (PL). Triploidy (three haploid sets of chromosomes) was the most common aberration, found in 42% of POCs following PL over the embryonic period. Over the same period, trisomies and monosomies were identified in 11.6% of POCs and subchromosomal aberrations in 4.2%. Whole and subchromosomal aberrations involved 17 autosomes, with chromosomes 3, 4, and 20 having the highest number of aberrations. Triploid fetuses had clear gross developmental anomalies of the brain. Collectively, data demonstrate that alterations in chromosome number contribute to PL similarly in women and mares, with triploidy the dominant ploidy type over the key period of organogenesis. These findings, along with highly conserved synteny between human and horse chromosomes, similar gestation lengths, and the shared single greatest risk for PL being advancing maternal age, provide strong evidence for the first animal model to truly recapitulate many key features of human miscarriage arising due to chromosomal aberrations, with shared benefits for humans and equids.
染色体异常是人类流产的常见原因,但在其他物种中很少报道。因此,目前缺乏可用于研究这种情况的适当动物模型。马提供了一种潜在的模型,因为母马接受了密集的妇科护理。这使我们能够在自然发生的妊娠丢失 (PL) 模型中研究 256 个妊娠产物 (POC) 中的染色体拷贝数异常的发生率。三倍体(三条单倍体染色体)是最常见的异常,在 PL 后胚胎期的 42%的 POC 中发现。在同一时期,11.6%的 POC 中发现了三体和单体,4.2%的 POC 中发现了亚染色体异常。全染色体和亚染色体异常涉及 17 条常染色体,3、4 和 20 号染色体的异常数量最多。三倍体胎儿的大脑有明显的大体发育异常。总的来说,数据表明染色体数目的改变在女性和母马中同样导致 PL,三倍体是器官发生关键时期的主要倍性类型。这些发现,以及人与马染色体之间高度保守的同线性、相似的妊娠长度,以及 PL 的最大单一风险是母马年龄的增长,为第一个真正再现由于染色体异常导致的人类流产的许多关键特征的动物模型提供了强有力的证据,这对人类和马属动物都有共同的好处。