Gut microbiota contributes to the development of endometrial glands in gilts during the ovary-dependent period

Background:The hyper-prolificacy Meishan gilts achieved a superior endometrial gland development(EGD)than white crossbred gilts during the ovary-independent period(before 60 d of age).Then,the EGD continues under the management of ovary-derived steroid hormones that regulated by gut microbiota(after 60 d of age).However,whether Meishan gilts’superiority in EGD lasting to the ovary-dependent period(after 60 d of age)and the role of gut microbiota in this period both remain unclear.Methods:Meishan gilts and Landrace x Yorkshire(LxY)gilts were raised under the same housing and feeding conditions until sexual maturity and then we compared their EGD and gut microbiota.Meanwhile,we transplanted fecal microbiota from Meishan gilts to L×Y gilts to explore the role of gut microbiota in EGD.We sampled plasma every 3 weeks and collected the uterus,ovary,liver,and rectal feces after the sacrifice.We then determined the hormone concentrations and expressions of the EGD-related genes.We also profiled the gut microbiota using 16S rDNA sequencing and metabolites of plasma and liver tissue using untargeted metabolomics.Finally,the correlation analysis and significant test was conducted between FMT-shifted gut microbes and EGD-related indices.Results:Meishan gilts have larger endometrial gland area(P<0.001),longer uterine horn length(P<0.01)but lighter uterine horn weight(P<0.05),a distinctive gut microbiota compared with L×Y gilts.Fecal microbiota transplantation(FMT)increased endometrial gland area(P<0.01).FMT markedly shifted the metabolite profiles of both liver and plasma,and these differential metabolites enriched in steroid hormone biosynthesis pathway.FMT increased estradiol and insulin-like growth factor 1 but decreased progesterone dynamically.FMT also increased the expression of the EGD-related genes estrogen receptor 1 gene,epithelial cadherin,and forkhead box protein A2.There is a significant correlation between FMT-shifted gut microbes and EGD-related indices.Conclusion:Sexually matured Meishan gilts achieved a superior EGD than LxY gilts.Meanwhile,gut microbiota contribute to the EGD potentially via regulating of steroid hormones during the ovary-dependent period.

Organoids as a model to study the human endometrium

The endometrium is composed of glandular and luminal epithelia supported by stromal connective tissue and multiple other cell types.It is a dynamic organ that undergoes physiological and functional alteration during the menstrual cycle.Organoids resemble the primary tissue of origin to recapitulate their corresponding biological and pathological characteristics.They are known for their ability to undergo extensive expansion while maintaining their genomic stability,facilitating their long-term storage and high-throughput screening.The development of the three-dimensional endometrial organoid system,which recapitulates the structural and functional characteristics of the endometrial glands,provides a powerful tool to study the normal endometrium and its related diseases.The Web of Science was searched for relevant literature using the keywords"endometrium","endometrial gland","organoid",and"culture model";a total of 134 articles were selected.In this review,the characteristics,applications,and limitations of endometrial epithelial organoids are discussed.