Control of oviductal fluid flow by the G-protein coupled receptor Adgrd1 is essential for murine embryo transit

Dysfunction of embryo transport causes ectopic pregnancy which affects approximately 2% of conceptions in the US and Europe, and is the most common cause of pregnancy-related death in the first trimester. Embryo transit involves a valve-like tubal-locking phenomenon that temporarily arrests oocytes at the ampullary-isthmic junction (AIJ) where fertilisation occurs, but the mechanisms involved are unknown. Here we show that female mice lacking the orphan adhesion G-protein coupled receptor Adgrd1 are sterile because they do not relieve the AIJ restraining mechanism, inappropriately retaining embryos within the oviduct. Adgrd1 is expressed on the oviductal epithelium and the post-ovulatory attenuation of tubal fluid flow is dysregulated in Adgrd1-deficient mice. Using a large-scale extracellular protein interaction screen, we identified Plxdc2 as an activating ligand for Adgrd1 displayed on cumulus cells. Our findings demonstrate that regulating oviductal fluid flow by Adgrd1 controls embryo transit and we present a model where embryo arrest at the AIJ is due to the balance of abovarial ciliary action and the force of adovarial tubal fluid flow, and in wild-type oviducts, fluid flow is gradually attenuated through Adgrd1 activation to enable embryo release. Our findings provide important insights into the molecular mechanisms involved in embryo transport in mice. Lack of correct embryo transport can cause ectopic pregnancy. Here, the authors show that female mice lacking the adhesion G-protein coupled receptor Adgrd1 are infertile, due to embryos being trapped in the ampulla as the result of dysregulated oviductal fluid flow

Oxidative Stress in Reproduction: A Mitochondrial Perspective

Mitochondria are fundamental organelles in eukaryotic cells that provide ATP through oxidative phosphorylation. During this process, reactive oxygen species (ROS) are produced, and an imbalance in their concentrations can induce oxidative stress (OS), causing cellular damage. However, mitochondria and ROS play also an important role in cellular homeostasis through a variety of other signaling pathways not related to metabolic rates, highlighting the physiological relevance of mitochondria–ROS interactions. In reproduction, mitochondria follow a peculiar pattern of activation, especially in gametes, where they are relatively inactive during the initial phases of development, and become more active towards the final maturation stages. The reasons for the lower metabolic rates are attributed to the evolutionary advantage of keeping ROS levels low, thus avoiding cellular damage and apoptosis. In this review, we provide an overview on the interplay between mitochondrial metabolism and ROS during gametogenesis and embryogenesis, and how OS can influence these physiological processes. We also present the possible effects of assisted reproduction procedures on the levels of OS, and the latest techniques developed to select gametes and embryos based on their redox state. Finally, we evaluate the treatments developed to manage OS in assisted reproduction to improve the chances of pregnancy