Menopause & ovarian aging: aging of the female reproductive tract

Welcome, everyone. Today I'll talk to you about "Menopause and Ovarian Aging" and this is Part 2 on this talk. My name is Mimi Ghosh. I'm an associate professor at the Department of Epidemiology at the Milken Institute School of Public Health George Washington University in Washington DC.

Today I will focus on the aging of the female reproductive tract, particularly ovarian aging in Part 2 of this talk.

I will begin with the biology of the female reproductive tract and then discuss aging and menopause associated changes.

In this next slide I show you the structure of the female reproductive tract which I will refer to as FRT and I'm showing you a schematic of the upper and the lower tract. The upper tract consists of the ovary and the Fallopian tubes and the uterus and then the lower tract is the vagina and the cervix. The cervix is also the endo and the ectocervix. But the ectocervix, if you look in the picture has multiple layers of cells. This is a thick epithelial layer that is difficult to breach by pathogens and then the endocervix is the monolayer that is right above the ectocervix.

There are multiple levels of immune protection in the female reproductive tract and I want to summarize some of these. On the right-hand side you see a schematic again showing you the ectocervix and the endocervix. You see the lower half of the reproductive tract has multiple layers of epithelial cells. This provides barrier protection against pathogen and then the upper part is a single layer of cells. There's a layer of mucus typically covering the epithelial cells which also provides protection and then everything else you see inside the epithelial cells are the stromal fibroblasts and then the immune cells that populate the reproductive tract. First level of protection is really the barrier which can be measured by something we call trans epithelial resistance which is basically measuring the strength of the barrier by measuring resistance to electric current. If you pass an electric current through this barrier, you will measure the resistance and know how strong the barrier is. Under the microscope it actually looks like this. The picture you see now with a nice cobblestone appearance in green that shows an intact barrier. Then you have the layer of mucus which is slippery and slimy and prevents pathogen from entering. We also think about the pH in the female reproductive tract. The vaginal pH is typically acidic which also stops pathogens from entering and then you have a whole host of mucosal immune responses. These are the immune responses that happen right there in the reproductive tract at the entry point of the pathogen. This is what the host and the pathogens meet and this is where you need the immediate innate immune protection. This mucosal immune response consists of pattern recognition receptors which are basically receptors that recognize something non-self as in a pathogen. It also consists of antimicrobial peptides, cytokines, chemokines, interferons proteases, a number of different types of immune cells such as T cells, B cells, macrophages, dendritic cells and natural killer cells, as well as antibodies. These all comprise the mucosal innate immune response. Further there is the microbiome which is protective. Vaginal microbiome has commensal bacteria which are beneficial typically Lactobacillus. These bacteria are protective.