Characteristics of the vaginal microbiome in women with premature ovarian insufficiency.

PURPOSE: To investigate the relationship between vaginal microbial community structure and premature ovarian insufficiency (POI). METHODS: Twenty-eight women with POI and 12 healthy women were recruited at Shenzhen Maternity and Child Healthcare Hospital between August and September 2020. Blood samples were collected for glucose tests and detection of sex hormone levels and vaginal secretions were collected for microbial group determination. Vaginal microbial community profiles were analysed by 16S rRNA gene sequencing using the Illumina MiSeq system (Illumina Inc., San Diego, CA, USA). RESULTS: Compared to the controls, the serum levels of follicle-stimulating hormone, luteinizing hormone, testosterone, and the follicle-stimulating hormone/luteinizing hormone ratio, significantly increased, and oestradiol and anti-Müllerian hormone levels significantly decreased in women with POI. Higher weighted UniFrac values were observed in women with POI than in healthy women. Bacteria in the genera Lactobacillus, Brevundimonas, and Odoribacter were more abundant in the microbiomes of healthy women, while the quantity of bacteria in the genus Streptococcus was significantly increased in the microbiomes of women with POI. Moreover, these differences in microbes in women with POI were closely related to follicle-stimulating hormone, luteinizing hormone, oestradiol, and anti-Müllerian hormone levels and to the follicle-stimulating hormone/luteinizing hormone ratio. CONCLUSIONS: Women with POI had altered vaginal microbial profiles compared to healthy controls. The alterations in their microbiomes were associated with serum hormone levels. These results will improve our understanding of the vaginal microbial community structure in women with POI. TRIAL REGISTRATION: CHICTR, ChiCTR2000029576 . Registered 3 August 2020 - Retrospectively registered, https://www.chictr.org.cn/showproj.aspx?proj=48844 .

Systemic changes in a mouse model of VCD-induced premature ovarian failure.

AIMS: Premature ovarian failure (POF) is a phenomenon in which the ovaries fail before the age of 40 years. Prior research has used a wide range of mouse models designed to reflect different causes of POF, including genetic factors, iatrogenic factors, and immune factors. The current study employed a mouse model of POF induced by 4-vinylcyclohexene diepoxide (VCD). VCD can specifically kill primordial and primary ovarian follicles, which destroys the follicular reserve and causes POF. The current study sought to specify and extend the applications of this model by examining the effect of timing and VCD dose and by exploring the effect of the model on systems outside of the ovaries. MATERIALS AND METHODS: A VCD-induced mouse model of POF was constructed using established methods (VCD injected continuously at a concentration of 160 mg/kg for 15 days). Evidence for a graded effect of VCD was observed using a range of concentrations, and the best windows for examining VCD's effects on follicles and associated tissues were identified. KEY FINDINGS: The mouse model used here successfully simulated two common complications of POF - emotional changes and decreased bone density. The model's application was then extended to examine the links between disease and intestinal microorganisms, and evidence was found linking POF to the reproductively relevant composition of the gut microbiota. SIGNIFICANCE: These findings provide novel methodological guidance for future research, and they significantly extend the applications and scope of VCD-induced POF mouse models.

Changes in the vaginal microbiota associated with primary ovarian failure.

BACKGROUND: Primary ovarian failure (POF) is defined as follicular failure in women of reproductive age. Although many factors are speculated to contribute to the occurrence of POF, the exact aetiology remains unclear. Moreover, alterations in the microbiome of patients with POF are poorly studied. RESULTS: This study investigated the vaginal microbiota of 22 patients with POF and 29 healthy individuals. High-throughput Illumina MiSeq sequencing targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene was used to evaluate the relationships between the vaginal flora and clinical characteristics of POF. Different from results of previous studies, we found that the diversity and richness of the vaginal flora of patients with POF was significantly different from those of healthy controls. Comparison of the vaginal flora of patients with POF with that of menopausal women revealed that the relative abundance of Lactobacillus was significantly reduced in the latter. A reduced abundance of Lactobacillus was furthermore associated with a lower pregnancy success rate. Of particular interest is that L. gallinarum especially appeared to be beneficially associated with reproductive-related indicators (FSH, E2, AMH, PRL) whilst L. iners appeared to have a detrimental effect. The result of the present study may enable the identification of microbiota associated with POF, however, further investigations of differences in the microbiota in the context of POF will enable a deeper understanding of the disease pathogenesis that involves modification of the vaginal microbiota. CONCLUSIONS: The present study identified the microbiota associated with POF. Further investigations on the differences in the microbiota in the context of POF will improve our understanding of the pathogenesis of the disease which involves modification of the vaginal microbiota.