Laboratoire Processus Dégénératifs, Stress et Vieillissement, Unité de Biologie Fonctionnelle et Adaptative (BFA), UMR 8251 CNRS, Université de Paris, 75205 Paris, France.
Université Paris-Saclay, UVSQ, INRAE, ENVA, BREED, 78350 Jouy-en-Josas, France.
Genes (Basel). 2021 Nov 16;12(11):1800. doi: 10.3390/genes12111800.
Down syndrome (DS) is the most common chromosomal disorder. It is responsible for intellectual disability (ID) and several medical conditions. Although men with DS are thought to be infertile, some spontaneous paternities have been reported. The few studies of the mechanism of infertility in men with DS are now dated. Recent research in zebrafish has indicated that overexpression of DYRK1A (the protein primarily responsible for ID in DS) impairs gonadogenesis at the embryonic stage. To better ascertain DYRK1A's role in infertility in DS, we investigated the effect of DYRK1A overexpression in a transgenic mouse model. We found that overexpression of DYRK1A impairs fertility in transgenic male mice. Interestingly, the mechanism in mice differs slightly from that observed in zebrafish but, with disruption of the early stages of spermatogenesis, is similar to that seen in humans. Unexpectedly, we observed hypogonadotropic hypogonadism in the transgenic mice.
唐氏综合征（DS）是最常见的染色体疾病。它可导致智力障碍（ID）和多种医学病症。尽管患有 DS 的男性被认为是不育的，但已有一些自发性生育的报道。目前，对 DS 男性不育机制的少数研究已经过时。最近在斑马鱼中的研究表明，DYRK1A 的过表达（DS 中主要导致 ID 的蛋白）会在胚胎期损害性腺发生。为了更好地确定 DYRK1A 在 DS 中不育的作用，我们在转基因小鼠模型中研究了 DYRK1A 过表达的影响。我们发现 DYRK1A 的过表达会损害转基因雄性小鼠的生育能力。有趣的是，该机制在小鼠中与在斑马鱼中观察到的略有不同，但与人类所见的情况类似，即破坏了精子发生的早期阶段。出乎意料的是，我们在转基因小鼠中观察到了促性腺激素低下性性腺功能减退症。
