Menstrual Fluid Factors Mediate Endometrial Repair

Menstruation is a process whereby the outer functionalis layer of the endometrium is shed each month in response to falling progesterone and estrogen levels in a non-conception cycle. Simultaneously with the tissue breakdown, the surface is re-epithelialized, protecting the wound from infection. Once menstruation is complete and estrogen levels start to rise, regeneration progresses throughout the proliferative phase of the cycle, to fully restore endometrial thickness. Endometrial repair is unique compared to tissue repair elsewhere in the adult, in that it is rapid, scar-free and occurs around 400 times during each modern woman's reproductive life. The shedding tissue and that undergoing repair is bathed in menstrual fluid, which contains live cells, cellular debris, fragments of extracellular matrix, activated leukocytes and their products, soluble cellular components and extracellular vesicles. Proteomic and other analyses have revealed some detail of these components. Menstrual fluid, along with a number of individual proteins enhances epithelial cell migration to cover the wound. This is shown in endometrial epithelial and keratinocyte cell culture models, in an ex vivo decellularized skin model and in pig wounds in vivo. Thus, the microenvironment provided by menstrual fluid, is likely responsible for the unique rapid and scar-free repair of this remarkable tissue. Insight gained from analysis of this fluid is likely to be of value not only for treating endometrial bleeding problems but also in providing potential new therapies for poorly repairing wounds such as those seen in the aged and in diabetics.

Relics and Historical Uses of Human Zootherapeutic Products in Contemporary Spanish Ethnoveterinary Medicine

(1) Background: this review documents the wide repertoire of practices and remedies based on the use of human-derived products in Spanish ethnoveterinary medicine (EVM) from the early 20th century to the present. These practices are compared with historical data and those of other countries; (2) Methods: a search using advanced functions in the most important databases in the fields of ethnobiology, EVM, folklore, and ethnography was performed. Information was obtained from 29 documentary sources; (3) Results: from the search of the literature, 46 use-reports related to the veterinary use of human urine, menstrual fluid, saliva, breast milk, and faeces were recorded. These zootherapeutic resources are/were used to treat 20 animal diseases, in particular dermatological ailments. In addition, many practices of the magical–religious type are documented; (4) Conclusions: the veterinary uses described and analysed here are fundamental to the development of therapeutic tools and creating teaching and learning processes in new popular veterinary practices adapted to the users and those who demand them. The information collected could form a scientific foundation for future inventories of local veterinary knowledge (LVK) and research addressing the discovery of new drugs for livestock. This work contributes to the inventory of some uses, traditional practices, and rituals seriously threatened by the progressive loss of LVK in Europe.

Comparative Study on Vit. E & Mefenamic acid vs Mefenamic acid alone on mean reduction in pain in Primary Dysmenorrhea

Background: Pelvic pain around the time of mensturation without any identifiable pathologic lesion present from menarche is called primary dysmenorrhea. The pain is believed to be related to prostaglandin (PG). Women with dysmenorrhoea have a relatively high concentration of PGF 2 alpha in menstrual fluid and suppression of PG synthesis has become the main treatment. Aim: To compare mean reduction in pain in patients presenting with primary dysmenorrhea given vitamin E & Mefenamic acid versus Mefenamic acid alone. Results: It was a randomized controlled trial which was conducted in Department of Obstetrics & Gynecology, THQ Raiwind Hospital, Lahore for 6 months duration w.e.f 01/02/2017 to 31/07/2017. In this study, 18(36%) in Vitamin-E group and 21(42%) in Mefenamic acid group were between 15-20 years while 32(64%) in Vitamin-E group and 29(58%) in Mefenamic acid group were between 21-25 years, mean±sd was calculated as 20.86±2.92 and 20.66±2.86 years respectively, mean dysmenorrheal pain at baseline was recorded as 50.06±10.27 in Vitamin-E group and 50.14±10.28 in Mefenamic acid group, p value < 0.754, showing that both groups are insignificant, mean dysmenorrheal pain after treatment was recorded as 20.50±10.04 in Vitamin-E group and 30.22±10.28 in Mefenamic acid group, p value was < 0.002 showing significant difference between the two group, comparison of mean reduction in dysmenorrheal pain after treatment was recorded as 20.56±0.91 in Vitamin-E group and 10.92±0.75 in Mefenamic acid group, p value was < 0.000, showing significant difference. Conclusion: We concluded that there is a significant mean reduction in dysmenorrhic pain in patients given Mefenamic Acid + Vitamen E as compared to patients given Mefenamic Acid alone. Keywords: Dysmenorrhic pain, Mefenamic Acid + Vitamen E, mean reduction in dysmenorrhic pain

Comparison of Organoids from Menstrual Fluid and Hormone-Treated Endometrium: Novel Tools for Gynecological Research

Endometrial organoids (EMO) are an important tool for gynecological research but have been limited by generation from (1) invasively acquired tissues and thus advanced disease states and (2) from women who are not taking hormones, thus excluding 50% of the female reproductive-aged population. We sought to overcome these limitations by generating organoids from (1) menstrual fluid (MF; MFO) using a method that enables the concurrent isolation of menstrual fluid supernatant, stromal cells, and leukocytes and (2) from biopsies and hysterectomy samples from women taking hormonal medication (EMO-H). MF was collected in a menstrual cup for 4–6 h on day 2 of menstruation. Biopsies and hysterectomies were obtained during laparoscopic surgery. Organoids were generated from all sample types, with MFO and EMO-H showing similar cell proliferation rates, proportion and localization of the endometrial basalis epithelial marker, Stage Specific Embryonic Antigen-1 (SSEA-1), and gene expression profiles. Organoids from different disease states showed the moderate clustering of epithelial secretory and androgen receptor signaling genes. Thus, MFO and EMO-H are novel organoids that share similar features to EMO but with the advantage of (1) MFO being obtained non-invasively and (2) EMO-H being obtained from 50% of the women who are not currently being studied through standard methods. Thus, MFO and EMO-H are likely to prove to be invaluable tools for gynecological research, enabling the population-wide assessment of endometrial health and personalized medicine.

Are You There, Law? It's Me, Semen

Joining a conversation about menstruation and the law, this Essay interprets “law” to mean regulation––a source of burden, constraint, and interference justified by reason. The object of my regulatory agenda is a substance perceived by Western thinkers at least since Aristotle as the superior counterpart to menstrual fluid.1 Traditions that celebrate semen as vital or affirmative, while recoiling from and controlling the other gendered emission that hurts no one, get reality backward. Law as burden, constraint, and interference ought to regulate semen and leave menstrual fluid alone. Contrast the two substances. One of them started out with the potentially useful function of building a uterine lining. That possibility concluded, menstrual fluid is benign. The other effluvium started out with the potentially useful function of launching a pregnancy. Pregnancy is a good thing when it is desired by the person who has to live with the bulk of pregnancy’s detriments. Along with its capacity to do an important job, semen causes quite the array of harms. A statute on point for this purpose, the Federal Hazardous Substances Act, regulates material that “may cause substantial personal injury or substantial illness during or as a proximate result of any customary or reasonably foreseeable handling or use.”2 Because semen “has the capacity to produce personal injury or illness to man through ingestion, inhalation, or absorption through any body surface,” it also aligns with the definition of “toxic” in the statute.3 Judges, policymakers, litigants, and ordinary people can all learn from well-established legal labels to understand semen as a stark example of an externality. Nothing in this statute impedes the characterization I propose: The FHSA lists substances that lie outside its purview,4 and semen is not among them. Labeling, containment, and emergency protocols—splash protection, if you like—are the hazardous-substance safety impositions I would apply to semen.

Menstruation Dysregulation and Endometriosis Development

Endometriosis is a common gynecological condition characterized by the growth of endometrial-like tissue outside of the uterus which may cause symptoms such as chronic pelvic pain or subfertility. Several surgical and medical therapies are available to manage symptoms, but a cure has yet to be determined which can be attributed to the incomplete understanding of disease pathogenesis. Sampson's theory of retrograde menstruation is a widely accepted theory describing how shed endometrial tissue can enter the peritoneal cavity, but other factors are likely at play to facilitate the establishment of endometriosis lesions. This review summarizes literature that has explored how dysregulation of menstruation can contribute to the pathogenesis of endometriosis such as dysregulation of inflammatory mediators, aberrant endometrial matrix metalloproteinase expression, hypoxic stress, and reduced apoptosis. Overall, many of these factors have overlapping pathways which can prolong the survival of shed endometrial debris, increase tissue migration, and facilitate implantation of endometrial tissue at ectopic sites. Moreover, some of these changes are also implicated in abnormal uterine bleeding and endometrial diseases. More research is needed to better understand the underlying mechanisms driving dysregulation of menstruation in endometriosis specifically and identifying specific pathways could introduce new treatment targets. Analyzing menstrual fluid from women with endometriosis for inflammatory markers and other biomarkers may also be beneficial for earlier diagnosis and disease staging.

Cyclical endometrial repair and regeneration

ABSTRACT Uniquely among adult tissues, the human endometrium undergoes cyclical shedding, scar-free repair and regeneration during a woman's reproductive life. Therefore, it presents an outstanding model for study of such processes. This Review examines what is known of endometrial repair and regeneration following menstruation and parturition, including comparisons with wound repair and the influence of menstrual fluid components. We also discuss the contribution of endometrial stem/progenitor cells to endometrial regeneration, including the importance of the stem cell niche and stem cell-derived extracellular vesicles. Finally, we comment on the value of endometrial epithelial organoids to extend our understanding of endometrial development and regeneration, as well as therapeutic applications.

1710. Comparison of herpes simplex prevalence in serum and semen-cervical sample of infertility patients: A systematic review and meta-analysis

Background Herpes simplex virus (HSV) is a common pathogen of sexually transmitted infections, however the role it plays in the development of infertility is unknown. In animal studies, inoculating murine rete testis with HSV-1 revealed irreversible atrophy of the germinal epithelium. Another study found that human herpesvirus 1 thymidine kinase (HHV-1 TK) protein disrupts spermatogenesis by creating immature sperm and accelerating apoptotic cell death in rodent. Although it is well established that herpes virus affects fertility in male animal models, the question remains as to the effect of HSV in human infertility. Routine testing of serum HSV IgG/IgM/DNA or HSV PCR in semen-cervical sample is not commonly done in clinical practice, and there are no set guidelines as when to screen. We aim to review the available literature and compare the prevalence of HSV in serum versus semen-cervical samples, focusing on the infertile patient population. Methods We searched PubMed, Embase, Cochrane Library, and ClinicalTrials.gov from inception to December 2019. Our search terminology included: “Herpes, Human herpesvirus, infertility.” Inclusion criteria required testing to be done on either serum, sperm, menstrual fluid, or endocervical sample in infertile patients. PRISMA Flow Diagram for study selection. Results 17 retrospective studies were included in this review. In the male-infertility cohort, a total of 11 studies were compared. The random-effects pooled prevalence was 12.7% in semen sample, and 16.8% in serum sample. In the female-infertility cohort, a total of 6 studies were compared. The random-effects pooled prevalence was 12.1% in menstrual fluid /endocervical sample, and 17.8% in serum sample. Figure 1. Studies enroll in this meta-analysis, Male Figure 2. Studies enroll in this meta-analysis, Female Conclusion The prevalence of HSV in semen-cervical sample was about 12%, compared to HSV in serum sample is about 17%. Therefore, HSV contribution to infertility will be overestimated when we use serum sample for diagnosis. It is noteworthy to mention that the seroprevalence of HSV IgG is much higher in general population, previously reported at 35% to 50%. In addition, given that current antiviral treatment for HSV has side effects that could cause infertility on its own, as seen in animal studies. More studies are needed to evaluate the role HSV plays in causation of infertility. Disclosures All Authors: No reported disclosures