Extracellular vesicle research in reproductive science— Paving the way for clinical achievements

Mammalian conception involves a multitude of reciprocal interactions via a molecular dialogue between mother and conceptus. Extracellular vesicles (EVs) are secreted membrane-encapsulated particles that mediate cell-to-cell communication in various contexts. EVs, which are present in seminal, follicular, oviductal, and endometrial fluids, as well as in embryo secretions, carry molecular constituents that impact gamete maturation, fertilization, early embryo development, and embryo-maternal communication. The distribution, concentration, and molecular cargo of EVs are regulated by steroid hormones and the health status of the tissue of origin, and thus are influenced by menstrual phase, stage of conception, and the presence of infertility-associated diseases. EVs have been recognized as a novel source of biomarkers and potential reproductive medicine therapeutics, particularly for assisted reproductive technology (ART). There are still many technological and scientific hindrances to be overcome before EVs can be used in clinical diagnostic and therapeutic ART applications. Issues to be resolved include the lack of standardized measurement protocols and an absence of absolute EV quantification technologies. Additionally, clinically suitable and robust EV isolation methods have yet to be developed. In this review, we provide an overview of EV-mediated interactions during the early stages of reproduction from gamete maturation to embryo implantation and then outline the technological progress that must be made for EV applications to be translated to clinical settings.

An Evaluation of Hot Water Intake and Relief from Menstrual Cramps among Healthy Females - A Cross Sectional Study

Background: Primary dysmenorrhea is menstrual pain that very women undergo during her menstrual phase. It may vary in its frequency and duration in each and every woman. Many home remedies have been followed by females to combat these menstrual cramps. One such treatment is intake of hot water for three days during the menstrual phase Objective: To aim of the study is to observe the changes experienced by female who consume hot water regularly during menstruation Methods: The study was conducted in 100 female subjects with regular cycles of menstruation. The participants were administered with a self developed questionnaire consisting of 16 questions relating to the menstrual cramps and the remedies they chose and their regularity of hot water intake and the relief they obtained. The responses were collected using google forms. Descriptive statistics, frequency analysis and chi square test was used to analyze the data. Results: The study observed that female subjects experienced better results after regular hot water intake during menstruation. It relieves menstrual cramps and improves mental health. Conclusion: The present study concluded that the majority of the population had a regular habit of taking hot water and experienced improvement and relief from menstrual cramps.

Effects of menstrual cycle on appetite-regulating hormones and energy intake in response to cycling exercise in physically active women

Although ample evidence supports the notion that an acute bout of endurance exercise performed at or greater than 70% of maximum oxygen uptake suppresses appetite partly through changes in appetite-regulating hormones, no study has directly compared the influence between the phases of the menstrual cycle in women. The present study compared the effects of an acute bout of exercise on orexigenic hormone (acylated ghrelin) and anorexigenic hormones (peptide YY and cholecystokinin) between the early follicular phase (FP) and the mid luteal phase (LP) of the menstrual cycle in physically active women. Ten healthy women (age, 20.6 ± 0.7 years) completed two 3.5-h trials in each menstrual phase. In both trials, participants performed cycling exercises at 70% of heart rate reserve (at a corresponding intensity to 70% of maximum oxygen uptake) for 60 min followed by 90 min of rest. Following 90 min of rest, participants were provided with an ad libitum meal for a fixed duration of 30 min. Blood samples and subjective appetite were collected and assessed before, during, immediately post-, 45 min post-, and 90 min post-exercise. The exercise increased estradiol (327 %) and progesterone (681 %) in the LP more than the FP respectively (P < 0.001, f = 1.33; P < 0.001, f = 1.20). There were no between-trial differences in appetite-regulating hormones, subjective appetite, or energy intake of ad libitum meal. These findings indicate that exercise-induced increases in ovarian hormones in the LP may not influence appetite-regulating hormones in physically active women.

Evaluation of Blood Pressure and Heart Rate Variability during Different Phases of Menstrual Cycle

Introduction: Every month, between puberty and menopause, a woman’s body goes through a number of changes to get it ready for a possible pregnancy. This series of hormone-driven events is called the menstrual cycle. A woman’s menstrual cycle is divided into three phases- proliferative phase, secretory phase and menstrual phase. The hormonal surge during each phase causes profound effects on the cardiovascular system as well. However, previous research reported conflicting results in this concept. Thus the controversial statements associating blood pressure and heart rate variability with menstrual cycle promoted this research. Objective: The aim of this study is to evaluate the blood pressure and heart rate variability during different phases of the menstrual cycle. Materials and Methods: 20 healthy women belonging to the proliferative, secretory and menstrual phase of the menstrual cycle were analyzed for autonomic functions tests using systolic blood pressure, diastolic blood pressure, pulse rate and heart rate variability. Results: It showed that there was a statistically significant increase in systolic blood pressure, diastolic blood pressure, and pulse rate during the secretory phase. There was an increase in heart rate variability during the menstrual phase but this was statistically insignificant. Conclusion: The study concluded that there were significant changes in blood pressure during the secretory phase and pulse rate and insignificant increase in heart rate variability during the menstrual phase. Thus, the study also concluded that sympathetic nervous activity in the secretory phase is significantly greater than in the proliferative phase, whereas parasympathetic nervous activity is predominant in the proliferative phase.

Sphingosine 1-Phosphate (S1P) in the Peritoneal Fluid Skews M2 Macrophage and Contributes to the Development of Endometriosis

Sphingosine 1-phosphate (S1P), an inflammatory mediator, is abundantly contained in red blood cells and platelets. We hypothesized that the S1P concentration in the peritoneal cavity would increase especially during the menstrual phase due to the reflux of menstrual blood, and investigated the S1P concentration in the human peritoneal fluid (PF) from 14 non-endometriosis and 19 endometriosis patients. Although the relatively small number of samples requires caution in interpreting the results, S1P concentration in the PF during the menstrual phase was predominantly increased compared to the non-menstrual phase, regardless of the presence or absence of endometriosis. During the non-menstrual phase, patients with endometriosis showed a significant increase in S1P concentration compared to controls. In vitro experiments using human intra-peritoneal macrophages (MΦ) showed that S1P stimulation biased them toward an M2MΦ-dominant condition and increased the expression of IL-6 and COX-2. An in vivo study showed that administration of S1P increased the size of the endometriotic-like lesion in a mouse model of endometriosis.

The expression of BECN1, LC3B, and BCL2 genes in eutopic endometrium of patients with adenomyosis: A cross-sectional study

Introduction: Both autophagy and apoptosis play a role in the cyclic remodeling of the endometrium. The abnormal regulation of genes and signaling pathways in the eutopic endometrium plays a role in the abnormal migration and implantation in adenomyosis. Objective: The present study investigates the mRNA expression of autophagy and apoptosis-related genes BECN1, LC3B, and BCL2 in the eutopic endometrium of patients with adenomyosis compared with healthy premenopausal women. Materials and methods: The present work was a cross-sectional study conducted between July 2018 and April 2019. The participants were 32 premenopausal women who attended the surgery for adenomyosis and other benign gynecological conditions. The participants were divided into two groups, with 16 women in the adenomyosis group and 16 healthy women in the control group. Endometrial tissues were collected during the proliferative menstrual phase for a quantitative real-time polymerase chain reaction. Results: The mRNA expression of BECN1, LC3B, and BCL2 were normalized by geometric mean mRNA expression of actin and GAPDH. There was no significant difference in mRNA expression for all three genes when comparing the control and adenomyosis groups. Conclusions: The mRNA expressions of autophagy-related genes BECN1 and LC3B and anti-apoptosis-related gene BCL2 were not significantly different in the eutopic endometrium of patients with adenomyosis compared with healthy premenopausal women during the proliferative menstrual phase.

Sonoelastographic assessment of the normal uterus and ovaries using the Shear Wave Elastography according to different menstrual phases

Objective: In most of the gynecological studies conducted using the Shear Wave Elastography (SWE) method in the literature, the menstrual cycle period was not taken into account. Current study, we aimed to describe the sonoelastographic features of normal myometrium and ovaries in healthy women and to define their variability during the different phases of the menstrual cycle using the SWE method. Material and methods: All cases were selected from individuals between the ages of 24-31, with regular menstrual cycles and no systemic disease. Each case was called in, 1-5th, 12-16th, 21-24th day of their menstrual cycles and was evaluated by B-mode imaging and SWE in pelvic ultrasonography. The relationship of menstrual phases with uterine and ovarian elasticity was investigated by comparing all measurements made in different menstrual phases. Results: No statistically significant difference was observed between the volume of right and left ovaries in terms (p> 0.05). There was no statistically significant difference in terms of elastography measurements obtained from the uterus, right and left ovaries for each menstrual phase according to Bonferroni Correction (p> 0.0163). Conclusion: Although there was a slight decrease in myometrial SWE measurements in the follicular phase, there was no significant difference regarding the SWE measurements of uterus and ovaries in early follicular, peri-ovulatory, and luteal menstrual stages. Further studies with a large number of participants are needed to suggest whether gynecological studies planned to be carried out with the shear wave elastography method should be planned in a specific menstrual phase.