Ovariectomy Induces Selective Alterations in Dura Mater Blood and Lymphatic Microvascular Network Architecture in Mice

TL;DR

Removing ovaries in mice causes specific changes in the blood and lymphatic vessels in the skull's dura mater, linked to hormonal deficiency and early fibrosis.

Contribution

This study reveals selective microvascular and profibrotic changes in the dura mater following ovariectomy, highlighting hormonal regulation of vascular architecture.

Findings

OVX reduces total microvessel length, mainly due to arteriolar shortening and fragmentation.

Lymphatic vessels near the coronal suture show increased surface area after OVX.

Elevated α-SMA and TGF-β levels suggest early profibrotic changes in the dura mater post-OVX.

Abstract

Ovarian hormones are essential regulators of vascular homeostasis, yet their deficiency’s effects on the meningeal microvasculature remain incompletely understood. We used high-resolution imaging to assess the cranial dura mater (CDM) blood and lymphatic microvasculature in ovariectomized (OVX) and control (intact or sham-operated) mice, followed by morphometric analysis of microvessel architecture. Immunofluorescent staining and Western blotting were employed to evaluate markers of vascular remodeling and profibrotic signaling. Blood microvascular quantification revealed a significant reduction in total microvessel length two weeks post-OVX, primarily due to arteriolar, but not venular, shortening. At the same time, the lengths of individual segments of both arterioles and venules were also significantly decreased, indicating microvascular fragmentation. Despite these changes, total vessel surface area remained preserved, suggesting compensatory dilation, particularly in arterioles. OVX also increased overall vessel tortuosity, again selectively affecting arterioles. Region-specific analysis of lymphatic networks associated with the coronal suture (CS) showed significantly increased surface area of podoplanin-positive lymphatic vessels. Elevated α-smooth muscle actin (α-SMA) expression in vascular and stromal compartments in OVX animals, along with increased transforming growth factor beta (TGF-β) levels, indicated early profibrotic changes. These findings highlight the selective vulnerability of arterial and lymphatic microvascular structures to hormonal deficiency post-OVX and suggest an association between hormonal status, microvascular remodeling, and profibrotic alterations in the CDM.

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