Scully Deirdre M, Xia Tian, Musina Guzel R, McCown Michaela A, Umezu Kohei, Kircher Bonnie K, Behringer Richard R, Larina Irina V
Department of Integrative Physiology, Baylor College of Medicine, Houston, TX, USA.
Department of Biomedical Engineering, University of Houston, Houston, TX, USA.
Biol Reprod. 2025 Apr 13;112(4):651-662. doi: 10.1093/biolre/ioaf005.
The physiological and clinical importance of motile cilia in reproduction is well recognized; however, the specific role they play in transport through the oviduct and how ciliopathies lead to subfertility and infertility are still unclear. The contribution of cilia beating, fluid flow, and smooth muscle contraction to overall progressive transport within the oviduct remains under debate. Therefore, we investigated the role of cilia in the oviduct transport of preimplantation eggs/embryos using a combination of genetic and advanced imaging approaches. We show that the region of the oviduct where cumulus-oocyte complex circling occurs, around the time of fertilization, is correlated with asymmetrical mucosal fold arrangement and non-radially distributed ciliated epithelium. Our results suggest that motile cilia, as well as mucosal fold asymmetry, may contribute to the local flow fields that help steer luminal contents away from the epithelial walls. We also present, in vivo, volumetric evidence of delayed egg transport in a genetic mouse model with disrupted motile cilia function in the female reproductive system. Females with Dnah5 deleted in the oviduct epithelium are subfertile and demonstrate disrupted motile cilia activity within the oviduct mucosa. Fifty percent of Dnah5 mutant females have delayed egg transport where cumulus-oocyte complexes did not progress to the ampulla at the expected time point and remained within the ovarian bursa. The integration of advanced imaging with genetic dysfunction of motile cilia provides valuable insights into oviductal transport. Potentially, these data could be valuable for better understanding and management of tubal pathologies and human infertility.
活动纤毛在生殖过程中的生理和临床重要性已得到充分认可;然而,它们在输卵管运输中所起的具体作用以及纤毛病如何导致生育力低下和不育仍不清楚。纤毛摆动、液体流动和平滑肌收缩对输卵管内整体渐进性运输的贡献仍存在争议。因此,我们结合遗传学和先进成像方法,研究了纤毛在植入前卵子/胚胎输卵管运输中的作用。我们发现,在受精前后,卵丘-卵母细胞复合体发生环绕的输卵管区域,与不对称的黏膜皱襞排列和非径向分布的纤毛上皮相关。我们的结果表明,活动纤毛以及黏膜皱襞不对称,可能有助于形成局部流场,从而帮助引导管腔内容物远离上皮壁。我们还在体内提供了证据,证明在雌性生殖系统中活动纤毛功能受损的基因小鼠模型中卵子运输延迟。输卵管上皮中Dnah5缺失的雌性生育力低下,且输卵管黏膜内的活动纤毛活性受到破坏。50%的Dnah5突变雌性存在卵子运输延迟,卵丘-卵母细胞复合体在预期时间点未进入壶腹部,而是留在卵巢囊内。先进成像与活动纤毛基因功能障碍的结合,为输卵管运输提供了有价值的见解。这些数据可能对于更好地理解和处理输卵管病变及人类不育症具有重要价值。