73: Importance of placental testing in congenital zika virus (zikv) infection and fetal malformation syndrome

Abstract

OBJECTIVE: There is growing evidence that microbial dysbiosis plays a role in obesity, insulin resistance, chronic inflammation and adverse perinatal outcomes. Polycystic ovary syndrome (PCOS) is a condition of hyperandrogenism, oligomenorrhea and polycystic ovarian morphology. The etiology of PCOS is not yet discerned, and there is potential for the microbiome to play a role in the pathogenesis of the disorder. In this study, we sought to characterize how androgens and diet could modulate the microbiome and associate this with fertility outcomes in our model of PCOS. STUDY DESIGN: Prior studies in rhesus macaques demonstrate exposure to testosterone (T) at adolescence followed by a westernstyle diet (WSD) recapitulates features of PCOS. In this study, juvenile females were treated with subcutaneous cholesterol (control) or T implants beginning at menarche, and fed either a standard (14% of calories from fat) or WSD (36% of calories from fat). This created 4 cohorts: (1) control (C), (2) T alone, (3) WSD alone and (4) T+WSD (n¼10/group). Anal samples were collected at baseline plus after 3,6,12 and 18 months of treatment. Additionally, samples were collected from the vagina and cervix during menses, follicular and luteal phases of the uterine cycle. DNA was extracted and subjected to 16S sequencing. The animals were then mated and fertility and fecundity were recorded. RESULTS: Beta diversity analysis demonstrated that the microbiome of the GI tract is altered by WSD (p¼0.001), but not T (p0.52). Additionally, we demonstrate that the cervicovaginal microbiomes vary over the menstrual cycle in C animals (p¼0.012). This menstrual cycle variation was pattern was abrogated with T (p¼0.24). Beta diversity analysis of reveals a statistically different microbiome in the genital tract of each cohort (p¼0.001). Furthermore, when females were mated, the control animals and WSD animals achieved a 70% pregnancy rate. Conversely, the T treated animals achieved a 40% pregnancy rate and the T+WSD animals had a 33% pregnancy rate with 2/3 pregnancies atypical. CONCLUSION: We show that both WSD and T distinctly affect the cervicovaginal microbiome. Dysbiosis is distinct in a group that is subfertile and has increased atypical pregnancy rates. We hypothesize that the dysbiosis of the genital tract microbiome may play a role in adverse fertility and pregnancy outcomes seen with PCOS.