BACKGROUND: Reducing cardiovascular disease burden among women remains challenging. Epidemiologic studies have indicated that polycystic ovary syndrome (PCOS), the most common endocrine disease in women of reproductive age, is associated with an increased prevalence and extent of coronary artery disease. However, the mechanism through which PCOS affects cardiac health in women remains unclear. METHODS: Prenatal anti-Müllerian hormone treatment or peripubertal letrozole infusion was used to establish mouse models of PCOS. RNA sequencing was performed to determine global transcriptomic changes in the hearts of PCOS mice. Flow cytometry and immunofluorescence staining were performed to detect myocardial macrophage accumulation in multiple PCOS models. Parabiosis models, cell-tracking experiments, and in vivo gene silencing approaches were used to explore the mechanisms underlying increased macrophage infiltration in PCOS mouse hearts. Permanent coronary ligation was performed to establish myocardial infarction (MI). Histologic analysis and small-animal imaging modalities (eg, magnetic resonance imaging and echocardiography) were performed to evaluate the effects of PCOS on injury after MI. Women with PCOS and control participants (n=200) were recruited to confirm findings observed in animal models. RESULTS: Transcriptomic profiling and immunostaining revealed that hearts from PCOS mice were characterized by increased macrophage accumulation. Parabiosis studies revealed that monocyte-derived macrophages were significantly increased in the hearts of PCOS mice because of enhanced circulating Ly6C ⁺ monocyte supply. Compared with control mice, PCOS mice showed a significant increase in splenic Ly6C ⁺ monocyte output, associated with elevated hematopoietic progenitors in the spleen and sympathetic tone. Plasma norepinephrine (a sympathetic neurotransmitter) levels and spleen size were consistently increased in women with PCOS when compared with those in control participants, and norepinephrine levels were significantly correlated with circulating CD14 ⁺⁺ CD16 ⁻ monocyte counts. Compared with animals without PCOS, PCOS animals showed significantly exacerbated atherosclerotic plaque development and post-MI cardiac remodeling. Conditional Vcam1 silencing in PCOS mice significantly suppressed cardiac inflammation and improved cardiac injury after MI. CONCLUSIONS: Our data documented previously unrecognized mechanisms through which PCOS could affect cardiovascular health in women. PCOS may promote myocardial macrophage accumulation and post-MI cardiac remodeling because of augmented splenic myelopoiesis.

Rationale: Gliomatosis peritonei (GP) refers to the implantation of glial tissue on the visceral and parietal peritoneal surface, often associated with immature teratoma. It is a rare condition and the pathogenesis is not fully understood. In addition, the indistinguishable radiological appearance of immature and mature teratomas, and limited pathology samples make an accurate diagnosis difficult in most cases. More importantly, patients are also at risk of recurrence after surgery. This report aims to describe the process of diagnosis and treatment of GP with immature teratoma. Patient concerns: The patient, a 38-year-old woman presented with GP complicated with immature teratoma after laparoscopic ovarian cyst excision. Diagnoses: On physical examination, a 15 cm-pelvic mass, with poor mobility, was palpated. And tumor marker demonstrated a moderate increase in α-fetoprotein and carbohydrate antigen 125. We suspected malignancy according to the comprehensive preoperative evaluation, the postoperative pathology revealed an immature teratoma of the left ovary and complicated with gliomatosis peritonei. Three months after the second surgery, possible recurrence of immature teratoma was considered and the patient underwent the third laparotomy. But the postoperative pathology indicated mature teratoma and mature glial components in the pelvic lesions. Interventions and outcome: The patient underwent 2 more surgical resections after the initial resection and 3 cycles of bleomycin, etoposide, and cisplatin regimen chemotherapy. She was regularly followed up in the outpatient after surgery, and no recurrence has been reported in the pelvic cavity till date. Lesson: The case illuminated that the primary diagnosis of GP complicated with immature teratoma is critical but highly challenging for both gynecologists and pathologists and more attention should be paid to “GP complicated with immature cystic teratoma” patients to avoid inappropriate treatment.