COVID-19 and Pregnancy: A Dangerous Mix for Bone Turnover and Metabolism Biomarkers in Placenta and Colostrum.

Background: In pregnant women, COVID-19 can alter the metabolic environment, cell metabolism, and oxygen supply of trophoblastic cells and, therefore, have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the bone turnover and endocrine function of several metabolic biomarkers in colostrum and placenta. Methods: One hundred and twenty-four pregnant mothers were recruited from three hospitals between June 2020 and August 2021 and assigned to two groups: Control group and COVID-19 group. Metabolism biomarkers were addressed in placental tissue and colostrum. Results: Lipocalin-2 and resistin levels were higher in the placenta, revealing an underlying pro-inflammatory status in the gestation period for mothers suffering from COVID-19; a decrease in GLP-1 and leptin was also observed in this group. As for adiponectin, resistin, and insulin, their concentrations showed an increase; a decrease in GLP-1, leptin, and PYY was also reported in the colostrum of mothers suffering from COVID-19 compared with the control group. Conclusions: As for bone turnover, placental samples from mothers with COVID-19 showed lower levels of OPG, while DKK-1 increased compared with the control group. Colostrum samples showed higher levels of OPG, SOST, and PTH in the COVID-19 group, a fact that could have noteworthy implications for energy metabolism, fetal skeletal development, and postnatal bone density and mineralization. Further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in infants' health.

Endometrial whole metabolome profile at the receptive phase: influence of Mediterranean Diet and infertility.

Introduction: Several metabolite classes have been identified in human endometrium, including lipids, nucleotides, amino acids, organic acids, and sugars. The first studies suggest the importance of metabolites in endometrial functions, as imbalance in uterine metabolites has been associated with low implantation rate and endometriosis. Nevertheless, most of studies have put emphasis on specific metabolite classes, and we lack the knowledge of the whole metabolome composition in human uterus. Further, a healthy dietary pattern has been shown to potentially protect against different endometrial dysfunctions and is a potential modulator of metabolomic composition and, consequently, the intrauterine microenvironment. The Mediterranean Diet (MD), characterized by a high intake of fruits, vegetables, cereals, nuts, legumes, fish, and olive oil, and a low consumption of meat, dairy products, and processed foods, has been associated with a wide range of benefits for health. Indeed, the MD pattern has displayed a beneficial role in endometriosis management and fertility; however, the relationship between the MD and the endometrial metabolome is still unknown. In our study, we set out to analyze receptive-phase endometrial metabolome profiles among women with infertility and their associations with MD. Methods: The study included women with male factor infertility (n=8), unexplained infertility (n=10), recurrent implantation failure (n=14), and endometriosis (n=13). The endometrial metabolome was analyzed with ultrahigh-performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS). The MD adherence of the participants was assessed using the 14-point MEDAS questionnaire of adherence to the MD. Results: We provide the whole metabolome profile of the endometrium, where 925 different metabolites were identified. Among these metabolites, lipids comprised the largest part, where polyunsaturated fatty acids (PUFAs) prevailed. Women with endometriosis and recurrent implantation failure were found to have lower levels of PUFAs compared to women with male factor and unexplained infertility (i.e., no clear endometrial alterations), identifying a metabolome profile associated with infertility diagnoses where altered endometrial functions are suspected. Moreover, MD adherence seemed to be associated with the endometrial metabolomic profile in a manner dependent on the health status of the uterus. Conclusion: The study findings provide insight into the molecular background of female infertility and lead to identification of potential molecular biomarkers and possibilities for modulating the endometrial microenvironment and, thereby, endometrial functions involved in embryo implantation and infertility.

Microbial composition across body sites in polycystic ovary syndrome: a systematic review and meta-analysis.

Polycystic ovary syndrome (PCOS) is an endocrine disorder affecting reproductive-aged women, but the cause remains unclear. Recent evidence has linked microbial composition with PCOS; however, the results are inconsistent. The aim of this systematic review was to gather current knowledge of the microbes across body sites (oral cavity, blood, vagina/cervix, gut) in women with PCOS, and meta-analyse the microbial diversity in PCOS. For this purpose, a systematic search using PubMed, Web of Science, Cochrane and Scopus was carried out. After selection, 34 studies met the inclusion criteria. Most of the studies associated changes in the microbiome with PCOS, whereas heterogeneity of the studies in terms of ethnicity, body mass index (BMI) and methodology, among other confounders, made it difficult to corroborate this relationship. In fact, 19 out of 34 of the studies were categorised as having high risk of bias when the quality assessment was conducted. Our meta-analysis on the gut microbiome of 14 studies demonstrated that women with PCOS possess significantly lower microbial alpha diversity compared with controls (SMD = -0.204; 95% CI -0.360 to -0.048; P = 0.010; I2 = 5.508, by Shannon Index), which may contribute to the development of PCOS. Nevertheless, future studies should specifically overcome the shortcomings of the current studies by through well planned and conducted studies with larger sample sizes, proper negative and positive controls and adequate case-control matching.

Microenvironment of the Lower Reproductive Tract: Focus on the Cervical Mucus Plug.

The female lower reproductive tract microbiota is a complex ecosystem comprising various microorganisms that play a pivotal role in maintaining women's reproductive well-being. During pregnancy, the vaginal microbiota undergoes dynamic changes that are important for a successful gestation. This review summarizes the implications of the cervical mucus plug microenvironment and its profound impact on reproductive health. Further, the symbiotic relationship between the vaginal microbiome and the cervical mucus plug is highlighted, with a special emphasis on how this natural barrier serves as a guardian against ascending infections. Understanding this complex host-microbes interplay could pave the way for innovative approaches to improve women's reproductive health and fertility.

COVID-19 during Gestation: Maternal Implications of Evoked Oxidative Stress and Iron Metabolism Impairment.

COVID-19 has reached pandemic proportions worldwide, with considerable consequences for both health and the economy. In pregnant women, COVID-19 can alter the metabolic environment, iron metabolism, and oxygen supply of trophoblastic cells, and therefore have a negative influence on essential mechanisms of fetal development. The purpose of this study was to investigate, for the first time, the effects of COVID-19 infection during pregnancy with regard to the oxidative/antioxidant status in mothers' serum and placenta, together with placental iron metabolism. Results showed no differences in superoxide dismutase activity and placental antioxidant capacity. However, antioxidant capacity decreased in the serum of infected mothers. Catalase activity decreased in the COVID-19 group, while an increase in 8-hydroxy-2'-deoxyguanosine, hydroperoxides, 15-FT-isoprostanes, and carbonyl groups were recorded in this group. Placental vitamin D, E, and Coenzyme-Q10 also showed to be increased in the COVID-19 group. As for iron-related proteins, an up-regulation of placental DMT1, ferroportin-1, and ferritin expression was recorded in infected women. Due to the potential role of iron metabolism and oxidative stress in placental function and complications, further research is needed to explain the pathogenic mechanism of COVID-19 that may affect pregnancy, so as to assess the short-term and long-term outcomes in mothers' and infants' health.

An integrated model with classification criteria to predict vaginal delivery success after cesarean section.

Background: Cesarean delivery (CD) is the most frequently performed surgical procedure worldwide. Trial of labor after cesarean (TOLAC) is associated with an increase in perinatal complications related to uterine rupture. However, in general, vaginal birth after cesarean (VBAC) is considered safe and women have less morbidity than those who undergo an elective repeat CD.Objective: To develop an integrated model with the best performance criteria for predicting vaginal delivery success after CD.Study design: Retrospective observational study including 2367 women who underwent a TOLAC. A predictive model using classification and regression tree modeling was constructed to predict vaginal delivery using maternal demographic, medical history, and labor predictors.Results: Vaginal delivery was best predicted by spontaneous onset of labor, estimated fetal weight <3775 g, maternal body mass index <25, previous CD as an elective or for fetal distress reasons, and interdelivery interval <2290 days. The algorithm showed a sensitivity of 75%, a specificity of 53%, and the area under the curve was 0.69.Conclusions: The classification and regression tree algorithm can be used to develop a predictive model for the success of TOLAC.