Defects in the maternal reproductive system that result in early pregnancy loss are important causes of human female infertility. A wide variety of biological processes are involved in implantation and establishment of a successful pregnancy. Although chromatin remodelers have been shown to play an important role in many biological processes, our understanding of the role of chromatin remodelers in female reproduction remains limited. Here, we demonstrate that female mice mutant for chromatin remodeler Cecr2 are subfertile, with defects detected at the peri-implantation stage or early pregnancy. Using both a less severe hypomorphic mutation (Cecr2^GT) and a more severe presumptive null mutation (Cecr2^Del), we demonstrate a clear difference in the severity of the phenotype depending on the mutation. Although neither strain shows detectable defects in folliculogenesis, both Cecr2^GT/GT and Cecr2^GT/Del dams show defects in pregnancy. Cecr2^GT/GT females have a normal number of implantation sites at embryonic day 5.5 (E5.5), but significant embryo loss by E10.5 accompanied by the presence of vaginal blood. Cecr2^GT/Del females show a more severe phenotype, with significantly fewer detectable implantation sites than wild type at E5.5. Some Cecr2^GT/Del females also show premature loss of decidual tissue after artificial decidualization. Together, these results suggest a role for Cecr2 in the establishment of a successful pregnancy.

中文翻译：

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植入失败和胚胎丢失导致染色质重塑剂 Cecr2 突变的雌性小鼠生育力低下

导致早期流产的母体生殖系统缺陷是导致人类女性不育的重要原因。多种生物过程涉及植入和成功妊娠的建立。尽管染色质重塑剂已被证明在许多生物过程中发挥重要作用，但我们对染色质重塑剂在女性生殖中的作用的理解仍然有限。在这里，我们证明了染色质重塑剂 Cecr2的雌性小鼠突变体不育，在植入期或妊娠早期检测到缺陷。使用不太严重的亚型突变 ( Cecr2 ^GT ) 和更严重的推定无效突变 ( Cecr2 ^Del），我们证明了表型严重程度的明显差异，具体取决于突变。尽管这两种品系均未显示出可检测到的卵泡发育缺陷，但Cecr2 ^GT/GT和Cecr2 ^GT/Del母系均显示出妊娠缺陷。Cecr2 ^GT/GT雌性在胚胎第 5.5 天 (E5.5) 具有正常数量的植入位点，但在 E10.5 时胚胎明显丢失并伴有阴道血。Cecr2 ^GT/Del雌性表现出更严重的表型，在 E5.5 时可检测的植入位点明显少于野生型。一些Cecr2 ^GT/Del雌性也表现出人工蜕膜后蜕膜组织过早丧失。总之，这些结果表明Cecr2在成功怀孕中的作用。