Vaginal biomechanical function in premenopausal and postmenopausal women with and without pelvic organ prolapse.

The vagina plays a vital role in childbirth, and compromised vaginal mechanical integrity can lead to pelvic organ prolapse (POP). Animal studies highlight the biaxial mechanical response of pelvic organs, however, it has not yet been assessed in the human vagina with POP. Therefore, the objective of this study was to quantify the biaxial biomechanical properties of vaginal tissue in pre-and postmenopausal women across POP stages.

The Benefits of Estradiol on Cognitive Aging in Rats Are Independent From Its Effects on Cardiometabolic Health.

Research in preclinical models of menopause indicates that exogenously administered estrogens positively affect cognitive aging. However, clinical evidence indicates that the effects of estrogen therapy on cognition are inconsistent and may be modulated by preexisting cardiometabolic conditions. The extent to which cardiometabolic health affects the cognitive outcomes of estrogen therapy remains unclear.

Pregnancy-Dependent Cardioprotection via GPER Activation in Dahl Salt-Sensitive Rats.

Background: Preeclampsia is a hypertensive disorder of pregnancy that affects multiple organs, including the heart, increasing long-term cardiovascular risks for both the mother and offspring. While the G protein-coupled estrogen receptor (GPER) has cardioprotective effects, its role in pregnancy-associated cardiac dysfunction, particularly in chronic hypertension, remains unclear, given the significant physiological adaptations that occur during pregnancy, including hormonal fluctuations and hemodynamic changes. This study investigated whether LNS8801, a selective and orally bioavailable GPER agonist, could improve cardiac function in virgin and pregnant Dahl salt-sensitive (SS/Jr) rats, a model of chronic hypertension exacerbated by pregnancy.

Hypertension disrupts the vascular clock in both sexes.

Blood pressure (BP) displays a circadian rhythm and disruptions in this pattern elevate cardiovascular risk. Although both central and peripheral clock genes are implicated in these processes, the importance of vascular clock genes is not fully understood. BP, vascular reactivity, and the renin-angiotensin-aldosterone system display overt sex differences, but whether changes in circadian patterns underlie these differences is unknown.

Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement.

Background: Sex hormones and sex chromosomes play a vital role in cardiovascular disease. Testosterone plays a crucial role in men's health. Lower testosterone level is associated with cardiovascular and cardiometabolic diseases, including inflammation, atherosclerosis, and type 2 diabetes.

Ovariectomy-Induced Arterial Stiffening Differs From Vascular Aging and Is Reversed by GPER Activation.

Background: Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging and whether activation of the G-protein-coupled estrogen receptor could reverse stiffness.

Methods: Female C57Bl/6J mice were ovariectomized at 10 weeks of age or aged to 52 weeks, and some mice were treated with G-protein-coupled estrogen receptor agonists.

In vivo noninvasive systemic myography of acute systemic vasoactivity in female pregnant mice.

Altered vasoactivity is a major characteristic of cardiovascular and oncological diseases, and many therapies are therefore targeted to the vasculature. Therapeutics which are selective for the diseased vasculature are ideal, but whole-body selectivity of a therapeutic is challenging to assess in practice. Vessel myography is used to determine the functional mechanisms and evaluate pharmacological responses of vascularly-targeted therapeutics.

Ovariectomy-Induced Arterial Stiffening Differs from Vascular Aging and is Reversed by GPER Activation.

Arterial stiffness is a cardiovascular risk factor and dramatically increases as women transition through menopause. The current study assessed whether a mouse model of menopause increases arterial stiffness in a similar manner to aging, and whether activation of the G protein-coupled estrogen receptor (GPER) could reverse stiffness. Female C57Bl/6J mice were ovariectomized (OVX) at 10 weeks of age or aged to 52 weeks, and some mice were treated with GPER agonists.

Connecting G protein-coupled estrogen receptor biomolecular mechanisms with the pathophysiology of preeclampsia: a review.

Background: Throughout the course of pregnancy, small maternal spiral arteries that are in contact with fetal tissue undergo structural remodeling, lose smooth muscle cells, and become less responsive to vasoconstrictors. Additionally, placental extravillous trophoblasts invade the maternal decidua to establish an interaction between the fetal placental villi with the maternal blood supply. When successful, this process enables the transport of oxygen, nutrients, and signaling molecules but an insufficiency leads to placental ischemia.

Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.

Research in preclinical models indicates that estrogens are neuroprotective and positively impact cognitive aging. However, clinical data are equivocal as to the benefits of menopausal estrogen therapy to the brain and cognition. Pre-existing cardiometabolic disease may modulate mechanisms by which estrogens act, potentially reducing or reversing protections they provide against cognitive decline.

High-plasma soluble prorenin receptor is associated with vascular damage in male, but not female, mice fed a high-fat diet.

Plasma soluble prorenin receptor (sPRR) displays sexual dimorphism and is higher in women with type 2 diabetes mellitus (T2DM). However, the contribution of plasma sPRR to the development of vascular complications in T2DM remains unclear. We investigated if plasma sPRR contributes to sex differences in the activation of the systemic renin-angiotensin-aldosterone system (RAAS) and vascular damage in a model of high-fat diet (HFD)-induced T2DM.

Dihydrotestosterone Induces Arterial Stiffening in Female Mice.

Background: Testosterone is the predominant sex hormone in men and is increased in women with polycystic ovarian syndrome. These patients also experience an increased risk for cardiovascular diseases including hypertension and arterial stiffness. Since our previous work shows an important role for the G protein-coupled estrogen receptor (GPER) in arterial stiffness, we hypothesized that other hormones including androgens may impact arterial stiffness in female mice via regulation of GPER.

Smooth muscle contribution to vaginal viscoelastic response.

Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial loading remains unknown. The vagina is a fibromuscular viscoelastic organ that is exposed to prolonged and increased pressures with daily activities and physiologic processes such as vaginal birth. The vagina changes in geometry over time under prolonged pressure, known as creep.

Estrogen-mediated mechanisms in hypertension and other cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of death globally for men and women. Premenopausal women have a lower incidence of hypertension and other cardiovascular events than men of the same age, but diminished sex differences after menopause implicates 17-beta-estradiol (E2) as a protective agent. The cardioprotective effects of E2 are mediated by nuclear estrogen receptors (ERα and ERβ) and a G protein-coupled estrogen receptor (GPER).

Sex differences in vascular aging and impact of GPER deletion.

Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein-coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice.

Efficacy of glucagon-like peptide-1 and estrogen dual agonist in pancreatic islets protection and pre-clinical models of insulin-deficient diabetes.

We study the efficacy of a glucagon-like peptide-1 (GLP-1) and estrogen dual agonist (GLP1-E2) in pancreatic islet protection. GLP1-E2 provides superior protection from insulin-deficient diabetes induced by multiple low-dose streptozotocin (MLD-STZ-diabetes) and by the Akita mutation in mice than a GLP-1 monoagonist. GLP1-E2 does not protect from MLD-STZ-diabetes in estrogen receptor-α (ERα)-deficient mice and fails to prevent diabetes in Akita mice following GLP-1 receptor (GLP-1R) antagonism, demonstrating the requirement of GLP-1R and ERα for GLP1-E2 antidiabetic actions.

NAMS 2021 Utian Translational Science SymposiumSeptember 2021, Washington, DCCharting the path to health in midlife and beyond: the biology and practice of wellness.

Charting the Path to Health in Midlife and Beyond: The Biology and Practice of Wellness was a Translational Science Symposium held on Tuesday, September 21, 2021. Foundational psychosocial and behavioral approaches to promote healthy aging and strategies to disseminate this information were discussed. The following synopsis documents the conversation, describes the state of the science, and outlines a path forward for clinical practice.

Biaxial Murine Vaginal Remodeling With Reproductive Aging.

Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown.

Glycolytic and Oxidative Phosphorylation Defects Precede the Development of Senescence in Primary Human Brain Microvascular Endothelial Cells.

Alterations of mitochondrial and glycolytic energy pathways related to aging could contribute to cerebrovascular dysfunction. We studied the impact of aging on energetics of primary human brain microvascular endothelial cells (HBMECs) by comparing the young (passages 7-9), pre-senescent (passages 13-15), and senescent (passages 20-21) cells. Pre-senescent HBMECs displayed decreased telomere length and undetectable telomerase activity although markers of senescence were unaffected.

Sex and the G Protein-Coupled Estrogen Receptor Impact Vascular Stiffness.

[Figure: see text].