A Lifelong Impact on Endometriosis: Pathophysiology and Pharmacological Treatment.

Endometriosis is a chronic inflammatory disease associated with bothersome symptoms in premenopausal women and is complicated with long-term systemic impacts in the post-menopausal stage. It is generally defined by the presence of endometrial-like tissue outside the uterine cavity, which causes menstrual disorders, chronic pelvic pain, and infertility. Endometriotic lesions can also spread and grow in extra-pelvic sites; the chronic inflammatory status can cause systemic effects, including metabolic disorder, immune dysregulation, and cardiovascular diseases. The uncertain etiologies of endometriosis and their diverse presentations limit the treatment efficacy. High recurrence risk and intolerable side effects result in poor compliance. Current studies for endometriosis have paid attention to the advances in hormonal, neurological, and immunological approaches to the pathophysiology and their potential pharmacological intervention. Here we provide an overview of the lifelong impacts of endometriosis and summarize the updated consensus on therapeutic strategies.

Oocyte-specific disruption of adrenomedullin 2 gene enhances ovarian follicle growth after superovulation.

Background: Adrenomedullin 2 (ADM2), adrenomedullin (ADM), and calcitonin gene-related peptides (α- and ß-CGRPs) signal through heterodimeric calcitonin receptor-like receptor/receptor activity-modifying protein 1, 2 and 3 (CLR/RAMP1, 2 and 3) complexes. These peptides are important regulators of neurotransmission, vasotone, cardiovascular development, and metabolic homeostasis. In rodents, ADM is essential for regulating embryo implantation, fetal-placental development, and hemodynamic adaptation during pregnancy. On the other hand, ADM2 was shown to affect vascular lumen enlargement, and cumulus cell-oocyte complex (COC) communication in rodent and bovine ovarian follicles. To investigate whether oocyte-derived ADM2 plays a physiological role in regulating ovarian folliculogenesis, we generated mice with oocyte-specific disruption of the Adm2 gene using a LoxP-flanked Adm2 transgene (Adm2 loxP/loxP) and crossed them with Zp3-Cre mice which carry a zona pellucida 3 (Zp3) promoter-Cre recombinase transgene. Results: While heterozygous Adm2 +/-/Zp3-Cre and homozygous Adm2 -/-/Zp3-Cre mice were fertile, Adm2 disruption in oocytes significantly increased the number of ovulated oocytes following a superovulation treatment. Oocyte-specific Adm2 disruption also significantly impaired the developmental capacity of fertilized eggs and decreased the size of the corpus luteum following superovulation, perhaps due to a reduction of ovarian cyclin D2-associated signaling. Conclusions: The disruption of intrafollicular ADM2 signaling leads to follicular dysfunction. These data suggested that oocyte-derived ADM2 plays a facilitative role in the regulation of hormonal response and follicle growth independent of the closely related ADM and CGRP peptides, albeit in a subtle manner.

Nasal Methicillin-Resistant Staphylococcus aureus Colonization in Patients with Type 1 Diabetes in Taiwan.

Nasal methicillin-resistant Staphylococcus aureus (MRSA) colonies are an essential reservoir of infection, especially for patients with diabetes. However, data on MRSA colonization in patients with type 1 diabetes are limited. We investigated the epidemiology of MRSA colonization in patients with type 1 diabetes. This prospective cross-sectional study was conducted in a medical center (Chang Gung Memorial Hospital) in Taiwan from 1 July to 31 December 2020. Nasal sampling and MRSA detection were performed. The molecular characteristics of MRSA isolates were tested, and factors associated with MRSA colonization were analyzed. We included 245 patients with type 1 diabetes; nasal MRSA colonization was identified in 13 (5.3%) patients. All isolates belonged to community-associated MRSA genetic strains; the most frequent strain was clonal complex 45 (53.8%), followed by ST59 (30.8%) (a local community strain). MRSA colonization was positively associated with age ≤ 10 years, body mass index < 18 kg/m2, and diabetes duration < 10 years; moreover, it was negatively associated with serum low-density lipoprotein cholesterol ≥ 100 mg/dL. No independent factor was reported. The nasal MRSA colonization rate in type 1 diabetes is approximately 5% in Taiwan. Most of these colonizing strains are community strains, namely clonal complex 45 and ST59.