Sex-related external factors influence pulmonary vascular angiogenesis in a sex-dependent manner

Abstract

Bronchopulmonary dysplasia (BPD) is a devastating disease with a significant sexual dimorphism where males have a disadvantage compared to their female counterparts. Although mechanisms behind this sexual dimorphism are poorly understood, sex differences in angiogenesis have been identified as one possible source of the male disadvantage in BPD. Pulmonary angiogenesis was assessed in vitro using a bead sprouting assay with pooled male or female human pulmonary microvascular endothelial cells (HPMEC, 18-19 weeks gestation, canalicular stage of human lung development) in standard (sex-hormone containing) and hormone-stripped medium. We identified sex-specific phenotypes in angiogenesis where male HPMECs produce fewer but longer sprouts compared to female HPMECs. The presence of sex hormones from standard culture medium modifies the male HPMEC phenotype with shorter and fewer sprouts but does not influence the female phenotype. Using a conditioned medium model, we further characterized the influence of the sex-specific secretome. Male and female HPMECs secrete factors that increase the maximum length of sprouts in female, but not male HPMECs. The presence of sex hormones abolishes this response. The male HPMEC secretome inhibits angiogenic sprouting in male HPMECs in the absence of sex hormones. Taken together, these results demonstrate that the pulmonary endothelial cell phenotypes are influenced by sex hormones and sex-specific secreted factors in a sex-dependent manner.

Stochastic to Deterministic: A straightforward approach to create serially perfusable multiscale capillary beds

“…The creation and then subsequent refinement and remodeling of a self-assembled vascular plexus results in a highly efficient hierarchical architecture. However, all vascular networks are not the same; studies have demonstrated that microvascular networks are distinct within different tissues and vary with sex (67–70). Remodeling of vascular networks is, in part, regulated by fluid flow and the local mechanical microenvironment and these factors continue to play a significant role in proper endothelial function throughout the entirety of the vessel lifespan (71–73).…”

A straightforward cell culture insert model to incorporate biochemical and biophysical stromal properties into transplacental transport studies

“…and naturally derived (e.g., collagen, hyaluronic acid, alginate, fibrin, etc. ), have been used for studies that mimic the ECM and can also allow for embedding stromal cells within the bulk of the hydrogel (22)(23)(24)(25); however, independent control of biophysical properties and protein or peptide identity are difficult and require more care.…”