25 Jul Early Brigham Study Uses Stem Cells To Restore Ovarian Function
Posted at 12:58h
in Author Interviews, Brigham & Women's - Harvard, Endocrinology, Fertility, Lancet, OBGYNE
MedicalResearch.com Interview with:
[caption id="attachment_60669" align="alignleft" width="150"] Dr. Anchan[/caption]
Raymond M. Anchan, MD, Ph.D.
Director, Stem Cell Biology and Regenerative Medicine Research Laboratory
Assistant Professor, Harvard Medical School
Obstetrics/Gynecology
Center for Infertility and Reproductive Surgery
Brigham and Women's Hospital
MedicalResearch.com: What is the background for this study?
Response: As a reproductive endocrinologist, I have the privilege of caring for patients who unfortunately experience premature ovarian insufficiency- Some of these patients are as young as 17 yo. Additionally, a significant number of patients over the years have been reproductive age women who have breast cancer and ovarian failure from chemotherapy. These patients have been my inspiration to try to find a treatment for them. Since my earlier days as a neurobiologist and stem cell scientist, it was a natural course for me to seek cell-based therapies that are patient specific using autologous iPSCs.
Dr. GALBIATI[/caption]
Francesca Galbiati, MD
Clinical/Research fellow in Endocrinology
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study?
Response: Arginine-vasopressin (AVP) is a neurohormone well known for its role in water balance regulation. It promotes renal water absorption in the kidney, to maintain normal sodium levels in the blood via a tightly controlled osmotic regulation. Besides AVP classical role, data have shown that AVP effects extend beyond water balance regulation. Animal studies have shown that AVP has metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice.
Furthermore, AVP is regulated differently in males and females, and affects cognition differently across sexes, a phenomenon called sexual dimorphism. However, it is unknown whether its dimorphism translates to metabolism. Also, findings on AVP metabolic role are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, which regulation is still largely unknown. We performed this study to better investigate AVP metabolic role, and explore sex differences. We hypothesized that AVP would be positively associated with BMI, adiposity, and lean mass (acting as a signal of energy availability). We also predicted that relationships between AVP and body composition measures would differ by sex. We used the AVP area under the curve around a standardized meal to better capture repeated measures in response to food intake (that directly impacts energy availability). This also allowed to avoid the possible risk of fluctuating AVP levels due to possible pulsatile secretion.
Dr. Goodrich[/caption]
Jesse Goodrich PhD
Assistant Professor
Department of Population and Public Health Sciences
Keck School of Medicine
University of Southern California
MedicalResearch.com: What is the background for this study?
Response: Per- and poly-fluoroalkyl substances (PFAS) are a group of persistent chemicals that are known to interfere with hormones and metabolism. In our previous research, we have found that PFAS exposure is associated several specific diseases, especially in children and adolescents. These include obesity, type 2 diabetes, liver disease, and even liver cancer. However, we are still only just starting to fully understand all of the health effects of the many different PFAS in existence. Previous studies have focused primarily on one or two main PFAS. However, there are over 9,000 known PFAS, and people are exposed not just to a single PFAS but to mixtures of many PFAS. Importantly, the combination of these chemical exposures may affect us differently than single exposures alone.
To address this challenge, we used an innovative approach to study design to examine how exposure to PFAS impacts biological processes which may underly the development of many different diseases in adolescents and young adults. To do this, we first measured thousands of naturally occurring chemicals, known as metabolites, in people's blood. Then, using a new biostatistical method developed by our team, we identified how exposure to a mixture of several PFAS impacted each individual chemical. Finally, we used this information to determine which biological processes are changed by PFAS exposure.
Dr. LeBoff[/caption]
Meryl S. LeBoff, MD
Dr. Manson[/caption]
JoAnn E. Manson, MD, DrPH
Professor, Epidemiology, Harvard T.H. Chan School Of Public Health
Michael and Lee Bell Professor of Women's Health, Medicine, Harvard Medical School
Chief, Preventive Medicine, Brigham And Women's Hospital
Co-Director, Womens Health, Brigham And Women's Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Osteoporosis is a major public health problem. Although supplemental vitamin D has been widely used to reduce the risk of fractures in the general population, studies of the effects of vitamin D on fractures, the most important bone health outcome, have been conflicting.
Randomized controlled trials, the highest quality studies, from around the world have shown benefit, no effect, or even harm of supplemental vitamin D on risk of fractures. Some of the trials used bolus dosing, had small samples sizes or short study duration, and co-administered calcium. No large RCTS of this scale tested whether daily supplemental vitamin D (without co-administration with calcium) prevented fractures in the US population.
To fill these knowledge gaps, we tested the hypothesis in this ancillary study to VITAL, whether daily supplemental vitamin D3 reduced the risk of incident total, non-spine and hip fractures in women and men in the US.
Dr. Grant[/caption]
Leilah K. Grant, PhD
Postdoctoral Research Fellow in Medicine
Brigham and Women’s Hospital
Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: The prevalence of obesity increases in women around the age of menopause which increases the risk of diseases like diabetes and heart disease. Changes in hormones, like estrogen, are thought to contribute to weight gain during menopause, but other common symptoms of menopause such as sleep interruption may also play a role. While short sleep is known to adversely affect metabolism, little is known about the metabolic consequences of the type of sleep disruption most common in menopausal women – increased nighttime awakenings (i.e., sleep interruption) caused by hot flashes, but no change in overall sleep duration. We therefore did this study to see how an experimental model menopause-related sleep interruption would affect metabolic outcomes that may contribute to weight gain. 
Ning Ding[/caption]
Ning Ding MPH, PhD candidate
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