Study On The Mechanism Of Zinc Transporter Catsup Affecting Female Reproduction

With the improvement of people's living standards and the gradual enhancement of health awareness,the functional food industry has developed rapidly.At the same time,the research on dietary nutrition and health is also deepening.Zinc is an essential dietary nutrient for human body,but the body can't synthesize it by itself.It needs to be absorbed from the diet to meet the needs of life activities.At present,there are many zinc deficient people in the world.They may eat little food rich in dietary zinc or food rich in zinc absorption inhibitors.Zinc homeostasis is closely related to reproductive health,including sperm development,ovulation,fetal development and delivery.For pregnant women,the lack of body zinc level will lead to the increase of fetal congenital malformation rate,slow growth,placental growth damage and other problems.Dietary zinc supplementation can significantly alleviate the symptoms,but the in-depth molecular mechanism is still unclear.Therefore,exploring the molecular mechanism of zinc ion affecting female reproduction can provide guidance for patients with reproductive diseases in daily diet and reproductive regulation,and also provide theoretical support for the research and development of related functional foods.Drosophila melanogaster is one of the most important model organisms in genetics and developmental biology,which is similar to mammalian ovulation.Therefore,Drosophila melanogaster ovary model is also used to study the mechanism of reproductive regulation.In addition,the Drosophila melanogaster model is also very suitable for the study of dietary nutrition regulation and trace metal metabolism.Zinc transporters ZIP family(Slc39A)and Zn T family(Slc30A)maintain intracellular zinc homeostasis and are conserved.Zinc transporter Catsup is located in Golgi apparatus and has functional homology with mammalian Zip7.Catsup mutation results in a decrease in the number of ovarian tubes and egg production,leading to reproductive dysfunction,but the specific molecular mechanism is still unclear.In this study,Catsup expression was specifically regulated in fat body and ovary of female Drosophila melanogaster to observe the effect on reproductive capacity and explore the mechanism.The main results are as follows:(1)Specifically knockdown of Catsup(Catsup RNAi)in fat body resulted in significantly decreased egg production.Mechanism studies found that Catsup RNAi caused abnormal accumulation of collagen and Notch protein in the fat body,resulting in secretion disorder,hindered its transport from the fat body to the ovary,resulting in insufficient collagen and Notch protein in the germrium;in addition,Catsup RNAi also reduced the expression level of DE-Cadherin in the germrium,affecting the maintenance of germ stem cells in the germrium.Genetic regulation of Catsup RNAi induced intracellular zinc abnormality or dietary zinc reduction can significantly save reproductive disorders.(2)The specific Catsup RNAi in the ovary leads to the decrease of egg production,abnormal ovarian morphology,and damage to the microenvironment(niche)structure at the top of the germrium,which is mainly composed of germ stem cells,terminal filament cells and cap cells.Further studies showed that Catsup RNAi reduced the number of germ stem cells,terminal filament cells and cap cells in germrium;in addition,the expression levels of collagen,Notch protein and DE-Cadherin protein related to ovarian structure maintenance were significantly decreased.Zinc supplementation can significantly save reproductive disorders by genetic regulation of Catsup RNAi induced intracellular zinc abnormalities or dietary levels.In conclusion,we used Drosophila melanogaster ovary as a model system to explore the molecular mechanism of zinc ion transport protein Catsup in female reproduction.This paper explores the molecular mechanism of Catsup in fat body and ovary,which can improve people's understanding of zinc ion affecting female reproduction,and lay a foundation for the development of functional food and health food in the future.