This research belongs to the field of obstetrics and gynecology. Developmental diseases refer to the poor health state of offspring after birth caused by abnormal gametogenesis/embryonic development. Hereditary birth defects refer to abnormal structure, function or metabolism of offspring caused by genetic factors, both of which seriously affect population quality. The innovative results of this project are as follows: [Main technical innovations] 1. Mechanism and risk assessment of development-derived diseases: The theoretical theory of gametogenic diseases has been proposed for the first time in the world, and the intergenerational and intergenerational genetic/epigenetic mechanisms of sperm/egg derived diseases have been conducted. (1) The discovery of the mechanism of sperm/ovum-derived diabetes confirmed that the maternal adverse environment affects the islet cells of the offspring through gametes, and the change of the imprinted gene in germ cells is the material basis of intergenerational inheritance. (2) Clarify that hyperglycemia before and during pregnancy can reduce myocardial ischemia tolerance in offspring, and pretreatment with antioxidants can improve myocardial ischemia and provide a target for disease intervention. (3) Confirm that malnutrition during pregnancy leads to susceptibility to asthma in offspring by reshaping the metabolic pathways of immune cells in offspring and regulating epigenetic modifications, and provide disease intervention strategies. (4) Reveal that high estrogen levels during pregnancy can increase the risk of neurocognitive abnormalities and thyroid dysfunction in offspring, and provide scientific basis for improving the safety of offspring with assisted reproductive technology (ART). 2. Early warning and early prevention and control of development-derived diseases: (1) It was found that channel proteins ENaC, CFTR, AQPs and methyltransferases regulate egg/embryo development and implantation; growth and differentiation factors affect ovarian function; and splicing variants of androgen receptor can cause hyperandrogenemia in PCOS. (2) The maternal estrogen threshold on the day of oocyte retrieval has been used as an important indicator in selecting embryo transfer or cryopreservation, effectively reducing low birth weight infants; clinical assistance in reducing androgens before pregnancy has become a routine treatment. (3) Obesity and high fat during early pregnancy were found to be independent risk factors for premature birth and obesity in offspring. After insulin treatment for gestational diabetes, the offspring still had susceptibility to diabetes, suggesting the importance of early intervention and follow-up of offspring. 3. Clinical precise prevention and control of genetic birth defects: (1) Create pre-implantation genetic testing (PGT) technology for monogenic genetic diseases based on high-throughput sequencing and haplotype analysis to overcome detection errors caused by allele tripping and meet clinical requirements. There is a need for large-scale PGT accurate diagnosis of monogenic genetic diseases, and the diagnosis compliance rate is 100%. (2) Create a high-throughput sequencing technology based on molecular coding, which can perform non-invasive prenatal testing of more than 40 common dominant single gene inherited diseases at one time, filling the current inability to conduct large-scale non-invasive prenatal screening for dominant single gene diseases internationally. (3) Integrate advanced molecular diagnostic technologies such as fluorescence in situ hybridization, chromosome microarrays, high-throughput gene sequencing, and high-throughput ligation probe reaction (HLPA) to achieve chromosome numerical/structural aberrations and precise genetic diagnosis of gene copy number/gene sequence mutations in children with genetic diseases and prenatal fetal samples. [Application Promotion] Based on the development and optimization of the three major technical systems, a domestic large-scale, technologically advanced, and well-system clinical application platform for source prevention and control of development-derived diseases and precise blocking of genetic birth defects has been created. Through pre-pregnancy maternal endocrine correction, More than 7,000 healthy children have been guaranteed; more than 30,000 non-invasive prenatal screenings, 22712 fetal genetic diagnosis and 2123 genetic disease families have been completed, and 2717 children with genetic diseases have been avoided. A total of 73 papers have been published, including 61 SCI papers, with a cumulative IF of 357. A single article has a maximum of 109 citations and 1 national invention patent has been obtained. Published 8 related monographs and took the lead in formulating ldquo; Expert Consensus on Preimplantation Genetic Diagnosis/Screening Technologyrdquo;. The research results have been promoted and applied in 49 hospitals in 23 provinces and cities across the country, and have received positive comments from domestic and foreign counterparts and internationally renowned publications.