Imbalance Of M1/M2 Macrophages In Ovaries Of Hypertensive Mice Is Associated With Reproductive Dysfunction And Lymphangiogenesis Conference Paper uri icon


  • Macrophages are the principal immune cells in ovaries. Besides protecting against invading pathogens and antigens, macrophages also play an essential role in folliculogenesis, ovulation, luteinization, lymphangiogenesis, and other functions. An imbalance in M1/M2 macrophages is observed in systemic circulation in patients and animals with hypertension (HTN). Although studies have demonstrated an association between HTN and reproductive dysfunction in females, the effect of HTN on ovarian M1/M2 ratio and lymphatics is largely unknown. We hypothesized that L-NAME-induced HTN (LHTN) and salt-sensitive hypertension (SSHTN) may increase the M1/M2 balance in ovaries which is associated with lymphangiogenesis and reproductive dysfunction in mice. Female mice were either provided L-NAME (0.5 mg/mL) in their drinking water for 3 weeks or L-NAME for 2 weeks, followed by a 2-week washout period and subsequent 3-week 4% high salt diet (SSHTN). Control mice (C) received tap water and normal diet. Flow cytometry analysis revealed a significant decrease in M1 (C: 46%1, LHTN: 33%2; p<0.05) and an increase in M2 (C: 7%1, LHTN: 12%1; p<0.05) macrophages in ovaries from LHTN mice. In SSHTN mice, ovaries had significantly increased M1 (C: 24%1, SSHTN: 44%2; p<0.05) and decreased M2 (C: 12%1, SSHTN: 4%1; p<0.05) macrophages. There was a significant increase in gene expression of the hormone receptors AR, FSHR, ERa, ERb, and LHR, and the steroidogenic enzymes StAR, 3bHSD, CYP11a1, and CYP17a1. Ovaries of hypertensive mice had a significant increase in gene expression of the lymphatic vessel markers Lyve-1, Podoplanin, and Prox-1, the lymphangiogenic growth factor VEGF-C and receptors VEGFR-2 and VEGFR-3. Taken together these data demonstrate that HTN disturbs M1/M2 macrophages in ovaries and is associated with reproductive dysfunction and lymphangiogenesis. Manipulation of M1/M2 ratio may be a therapeutic opportunity to improve reproductive health in hypertensive women.

published proceedings


author list (cited authors)

  • Navaneethabalakrishnan, S., Wilcox, B. K., Goodlett, B. L., & Mitchell, B. M.

citation count

  • 0

complete list of authors

  • Navaneethabalakrishnan, Shobana||Wilcox, Brooke K||Goodlett, Bethany L||Mitchell, Brett M

publication date

  • September 2021