In order to communicate between different tissues, the body uses molecular signals released by one cell and picked up by others. With age, some of these signal pathways can break down.

Long distance signaling, such as between the brain and ovaries, can occur through neurons, called neurotransmission, or through circulating hormones like progesterone in the bloodstream, called endocrine signaling. Aging can affect the type, strength, and fidelity of both of these types of signals and contribute to the rate of decline of the female reproductive tract. Some scientists believe signaling changes in the brain may also be the first domino to fall, triggering the processes that lead to ovarian aging.

GCRLE Grantee projects

Dr Holly Ingraham: The brain and ovaries participate in extensive crosstalk- hormones from the ovaries and developing eggs activate the hypothalamus of the brain, which in turn stimulates the pituitary gland to release hormones that affect the female reproductive system and the entire body. Recently, scientists have begun to pinpoint which specific estrogen-sensitive neurons mediate the various effects of sex hormones on physiology, metabolism and behavior. Many more of these remain to be uncovered. Dr Ingraham’s lab is searching for more of these neural circuits that have central roles in driving female physiology. They hope to find previously undiscovered pathways in the brain that remodel the workings of the ovary, believing that they may indicate the presence of a ‘master regulatory system’ of the brain on reproductive aging.

Dr Polina Lishko: Endocannabinoids- named for the plant that lead to their discovery- are neurotransmitters that affect many parts of human physiological function. Endocannabinoid signaling is closely tied to sex hormone activity: together they influence normal egg maturation in the ovaries. Research also suggests endocannabinoid levels decrease with aging. The Lishko lab has found that the removal of the gene for an enzyme that breaks down endocannabinoids leads to altered reproductive aging in mice. They are rigorously investigating the mechanism behind this phenomenon to answer questions about how it could be manipulated in healthy individuals, as well as how the endocannabinoid system is involved in ovarian aging more generally.

Dr Malak Olfat: Sympathetic neurons govern ‘rest and digest’ and other every-day automatic bodily processes. Ovaries and their vasculature are contacted by many sympathetic neurons. Mounting evidence suggests that both aging and menopause are accompanied by an increase in sympathetic neurotransmission, a phenomenon that can be seen reflected in the increase in metabolic conditions with age, such as obesity and diabetes. These conditions also in turn compromise ovarian function and egg quality. Dr Malak is mapping the neurons that connect to the ovaries and characterizing the changes they undergo with age. By blocking neurotransmission along these neurons, she is assessing whether pharmacological interventions aimed at these cells can alleviate some of the negative effects of ovarian decline.