Abstract

Long term heat exposure (HE) leads to estrous cycle disorder (ECD) in female rats and damages reproductive function. However, the regulation mechanism of vaginal microorganisms and serum metabolomics remains unclear. This study aimed to explore the effects of microbes on the vaginal secretions of rats with ECD and describe the serum metabolomics characteristics and their relationship with vaginal microorganisms. The alterations in the serum levels of neurotransmitters were used to verify the possible regulatory pathways. The relative abundance, composition, and colony interaction network of microorganisms in the vaginal secretions of rats with ECD changed significantly. The metabolomics analysis identified 22 potential biomarkers in the serum including lipid metabolism, amino acid metabolism, and mammalian target of rapamycin and gonadotropin-releasing hormone (GnRH) signaling pathways. Further, 52 pairs of vaginal microbiota–serum metabolites correlations (21 positive and 31 negative) were determined. The abundance of Gardnerella correlated positively with the metabolite L-arginine concentration and negatively with the oleic acid concentration. Further, a negative correlation was found between the abundance of Pseudomonas and the L-arginine concentration and between the metabolite benzoic acid concentration and the abundance of Adlercreutzia. These four bacteria–metabolite pairs had a direct or indirect relationship with the estrous cycle and reproduction. The glutamine, glutamate, and dopamine levels were significantly uncontrolled. The former two were closely related to GnRH signaling pathways involved in the development and regulation of HE-induced ECD in rats. Serum neurotransmitters partly reflected the regulatory effect of vaginal microorganisms on the host of HE-induced ECD, and glutamatergic neurotransmitters might be closely related to the alteration in vaginal microorganisms. These findings might help comprehend the mechanism of HE-induced ECD and propose a new intervention based on vaginal microorganisms.

Highlights

  • Women have a low tolerance to a high-temperature environment (Marsh and Jenkins, 2002)

  • A total of 44 rats were randomly divided into two groups: (1) control group (C group)—the animals were fed under standard temperature and humidity conditions; and (2) heat exposure (HE) group (H group)—each model animal was exposed to heat (38°C ± 0.5°C; relative humidity 55% ± 5%) for 2 h/day (9:00–11:00) in a smallanimal heat chamber (Zheng et al, 2019; An et al, 2020)

  • Structural Diversity of Vaginal Microbiota The characteristic spectra of vaginal secretions were evaluated using 16S 16S ribosomal deoxyribonucleic acid (rDNA) gene sequencing to investigate the differences in the structural diversity of vaginal microbiota between rats with estrous cycle disorder (ECD) and control rats

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Summary

Introduction

Women have a low tolerance to a high-temperature environment (Marsh and Jenkins, 2002). Long-term heat exposure (HE) has noticeable adverse effects on female mammals. Emerging evidence has confirmed that HE can lead to female endocrine disorders and ovarian dysfunction (Dickson et al, 2018), affect rat ovarian cell proliferation and apoptosis, induce ovarian hormone over secretion (Sirotkin, 2010), destroy hormone balance (Li et al, 2017), increase sensitivity of granulosa cells to apoptosis (Luo et al, 2016), and so on. Many studies reported the damage of HE-induced female reproductive function, yet its mechanism has not been fully elucidated. The scope of an environment of high temperature has expanded, and the period of high temperature is prolonged. The study on the mechanism of the effect of HE on female reproduction is both necessary and indispensable

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