A Study On The Relationship Between Reproductive Hormones And Organismic Microbiome

Research Objectives In recent years,the prevalence of infertility among Chinese couples of childbearing age has been on the rise.This phenomenon has become one of the important issues in the social development.It is suggested that the study of female fertility is a complex systemic research.Reproductive function rely on the normal running of the neuroendocrine system,and closely related to endocrine,metabolism and immune system.A dozen of clinical studies proved that vaginal and intestinal microbiota might affect the female reproductive environment and reproductive endocrine through multiple pathways,including immunity,inflammatory response,endocrine,and metabolism.This study attempted to analyze the relationship between the organismic microbiome and reproductive endocrine and its mechanism.Experimental MethodsUsing the 16 S rRNA gene high-throughput sequencing,we compared the vaginal microbiota between 85 reproductive-age women and 50 post-menopausal women.A variety of computational models,including Random Forests Model,RDA analysis,and Spearman correlation analysis,were applied to analyze the correlation between the bacterial genera and clinical indicators related to reproductive function,including female age,AFC,AMH,FSH,LH and vaginal pH environment.In the second part,we used DHEA to induce hyperandrogenism model in rats,and then studied the dynamic changes of intestinal microbiota between eight hyperandrogenism rats and five controls by 16 S rRNA gene sequencing during the five weeks.We then analyzed the effect of hyperandrogenism on gut microbiota in rats,and the related function and metabolic pathways.ResultsCompared with the reproductive-age group,the vaginal microbiota abundance and diversity in the post-menopausal group were significantly increased(p <0.05).The abundance of Lactobacillus in the reproductive-age group was significantly higher than the post-menopausal group(p <0.05).In the post-menopausal group,the abundances of Prevotella,Streptococcus,Veillonella,Dialister,and Atopobium were suggestively higher(p <0.05).It was found that many kinds of vaginal bacteria were correlated with the vaginal pH environment,age,and reproductive endocrine indices.The vaginal bacteria associated with well reproductive function,including Lactobacillus and Bifidobacterium,related to the amino sugar and nucleotide sugar metabolism,steroid hormone synthesis,and cytochrome P450 metabolism.The genus of vaginal bacteria associated with poor reproductive function,including Gardnerella,Veillonella,Prevotella,Dialister,Streptococcus,Bacteroides,related to the lipopolysaccharide biosynthesis,histidine metabolism,and N-glycan biosynthesis.As time went by,the abundance of the gut microbiota in the hyperandrogenism group increased(p<0.05).Prevotella increased in the intestinal flora of control rats(p < 0.05)and Bacteroides decreased gradually(p < 0.05).In the hyperandrogenism group,however,there was a significant decrease in Alloprevotella(p <0.001).The abundance of Parasutterella in the hyperandrogenism group was significantly higher than that in the control group(p<0.05).The significantly different gut bacteria in the hyperandrogenism group were Alphaproteobacteria,Betaproteobacteria,Deltaproteobacteria,Burkholderiales,Elusimicrobia,et al.,related to glycan biosynthesis and metabolism,TCA cycle,coenzyme and vitamin metabolism,primary immune deficiency,renin-angiotensin system.The significantly different gut bacteria in the controls were Psychrobacter,Odoribacter,and Moraxellaceae,mainly related to endocytosis,glycosaminoglycan degradation,and GnRH signaling pathways,et al.ConclusionsFrom reproductive age to menopause,the structure of female vaginal microbiota changed markedly.The vaginal microbiota was closely related to female vaginal pH value,age,and reproductive endocrine.There is a relationship between reproductive tract environment and vaginal microbiota.Vaginal microbiota might affect the reproductive endocrine and reproductive function through various physiological and pathological mechanisms,including immunity,metabolism,and endocrine.By detecting the female vaginal microbiota,it helps to get biomarkers to evaluate the normality of reproductive tract environment and contributes to the assessment of reproductive endocrine and reproductive function.Hyperandrogenism could change the gut microbiota of rats,and affects the glucose &lipid metabolism,renin-angiotensin system and reproductive endocrine through the related functions of the bacterial genera,thereby causing the pathological changes of polycystic ovary syndrome.Analysis of the association between hyperandrogenism and gut microbiota may help to study their important roles in the pathogenesis of PCOS and provide further research strategies for the clinical diagnosis and treatment of polycystic ovary syndrome,from the perspective of microbiology and reproductive endocrinology.