High‐temperature exposure is detrimental to women’s reproductive health; however, the impact caused by long‐term high temperature is not comprehensive, and a stable model of estrous cycle disorder induced by a high temperature is yet lacking. Herein, we aimed to establish a stable and effective model of estrous cycle disorder in female rats induced by long‐term heat stress to study its physiological and pathological characteristics and explore the underlying mechanism. In the present study, female Sprague‐Dawley rats with normal estrous cycles were exposed to the temperature of 38 ± 0.5^°C, relative humidity (RH) of 55 ± 5% (2 h/d, 1 time/d) hot cabin at more than 90 days. Consequently, after long‐term heat stress, no difference was detected in body weight and rectal temperature, but the estrus cycle was prolonged, the uterine organ index was increased, pathological changes occurred, the increase latitude of stress hormones heat shock protein 70 (Hsp70) and corticosterone (CORT) decreased, estradiol (E₂) and luteinizing hormone (LH) levels decreased, follicle stimulating hormone (FSH) and prolactin (Prl) levels increased, gonadotropin‐releasing hormone (GnRH) and thyroid hormone (T₄) showed no difference, and insulin (INS) decreased significantly. Moreover, the mRNA expression of the sex hormone receptor in the uterus and ovary was altered. Therefore, the estrous cycle disorder in female rats can be induced by regular heat stress for 90 days, which can be considered the pioneer method. Subsequently, prominent physiological and pathological characteristics and disruption in the hypothalamic‐pituitary‐gonadal (HPG) axis were noted.

Female reproductive system diseases caused by exposure to a cold environment are widely considered as important human health challenges. Although the projection of female reproduction in cold temperature has been studied, a holistic view on the probable effects of cold exposure on the functions of the female reproductive system has not been achieved. Our aim was to evaluate the effects of cold exposure to the functions of the ovary and uterus in female rats. For this purpose, female rats were randomly grouped as follows: (1) the cold group was exposed to -10°C, 4 h per day for 2 weeks, and (2) the normal temperature (23 ± 1°C) group was used as control. Alterations were observed in different parameters, including body weight gain, organ coefficients, estrus cycle, and pathology of the cold-exposed female rats. Similarly, the serum reproductive hormones and mRNA expression were evaluated. Cold exposure induced estrus cycle irregularity and some alterations in the morphology of the ovary. Cold exposure impairs the function of the ovary probably by changing the level of serum LH and increasing LHR expression. Cold exposure induced a significant reduction of uterine epithelium height. Cold exposure causes alterations in the morphology of the uterus probably because of the effect of progesterone, the increase in the PR level, and the decrease in the ER level.

Energy homeostasis of mammals during cold exposure involves complicated neural regulation and is affected by gut microbiota. However, the regulatory mechanism remains unclear partially due to a lack of comprehensive knowledge of the signaling molecules involved. Herein, we performed region-resolvable quantitative profiling of the brain peptidome using cold-exposed mouse models and interrogated the interaction between gut microbes and brain peptides in response to cold. Region-specific alterations in the brain peptidome were observed during chronic cold exposure and were correlated with gut microbiome composition. Several proSAAS-derived peptides exhibited a positive correlation with Lactobacillus. The hypothalamus–pituitary axis exhibited a sensitive response to cold exposure. We obtained a candidate pool of bioactive peptides that potentially participate in the regulation of cold-induced energy homeostasis. Intervention with cold-adapted microbiota in mice decreased the abundance of hypothalamic neurokinin B and subsequently contributed to shifting the fuel source for energy consumption from lipids to glucose. Collectively, this study demonstrated that gut microbes modulate brain peptides contributing to energy metabolism, providing a data resource for understanding the regulatory mechanism of energy homeostasis upon cold exposure.

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.

Concern has been growing over the potential hazard of nanoparticles to human health because of increasing ambient particulate air pollution.