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Uterus

Studies of the Complexities of the Human Female Reproductive System

The Human Female Reproductive System and Associated Cancers

The female reproductive system is complex. Female gametes, eggs or ova, develop and mature in the two ovaries. Once every month, an egg exits either ovary into the fallopian tube, where it travels until it enters the uterus, or womb. If fertilization does not occur, the egg exits the uterus through the cervix into the vagina, and is expelled from the body. During this time, the epithelial lining of the uterus, the endometrium, thickens in preparation for implantation of a fertilized egg. In the absence of implantation, the endometrium is shed in a process called menstruation.

Endometrial cancer is the most common cancer type that occurs in female reproductive organs. There are roughly 61,380 new endometrial cancer cases diagnosed each year, and almost 11,000 annual deaths. Additionally, one in ten women suffer from endometriosis, a non-malignant disorder that occurs when endometrial tissue grows outside the uterus, causing pain and discomfort, particularly during menstruation. The cause of endometriosis is unknown, but is associated with abnormal endometrial remodeling, which is regulated, in part, by uterine fibroblasts.

Uterine fibroblasts are stromal cells of the uterine wall that induce tissue remodeling through production of matrix remodeling enzymes, known as matrix metalloproteases (MMPs), in response to chemokine and cytokine signaling. Fibroblast-mediated remodeling is important for uterine homeostasis, menstruation, pregnancy, and parturition (the process of labor).

Cervical cancer is diagnosed in 12,820 women per year and causes 4,210 annual deaths. One of the major risk factors for cervical cancer is human papillomavirus (HPV) infection, which is extremely common. However, due to improved screening methods, the rate of cervical cancer has significantly decreased over the last few decades.

Vaginal cancer is more rare, with only 4,810 new cases each year and 1,240 annual deaths. The vaginal canal is lined by an epithelial cell layer, which is composed of squamous epithelial cells, the cell type in which vaginal cancer is initiated. Therefore, the most common type of vaginal cancer is squamous cell carcinoma.

Uterine sarcoma occurs in the smooth muscle cells of the uterus that regulate uterine contraction, performing a critical function during labor and childbirth. Only 4,910 new cases of uterine sarcoma are diagnosed each year. Uterine smooth muscle cells are also the site of uterine fibroid development. Uterine fibroids are benign tumors that may cause pain and discomfort, but are not a cause of malignancy.

Lifeline® Female Reproductive Cell Types

Lifeline® provides multiple female reproductive cell types that can be used to study normal physiology and homeostasis, as well as the cancers and disorders described above. Our catalog includes:

In addition, our female reproductive cells are optimized for growth in specialized media that is free of phenol red, which can bind estrogen receptors and cause off-target estrogen signaling effects. ReproLifeFemale Reproductive  medium is optimized for growth of endometrial and vaginal epithelial cells, VascuLife® SMC media is optimized for growth of uterine smooth muscle cells, and FibroLife® S2 media is optimized for growth of uterine fibroblast cells.

In 2015, Pabona and colleagues published a study using Lifeline® uterine smooth muscle cells, cultured in VascuLife® SMC media to study the role of progesterone signaling in early- and late-term pregnancy. Parturition is a highly regulated process that depends on signaling cues from multiple avenues, including progesterone signaling, to initiate smooth muscle cell contraction. In this study, the authors obtained biopsies from the myometrium (uterine smooth muscle layer) of women who underwent cesarean delivery (C-section) and found that women with late-term pregnancy had decreased levels of myometrial progesterone receptors A and B (PGR-A, PGR-B), as well as Kruppel-like factor 9 (KLF9).

Using Lifeline® uterine smooth muscle cells lacking KLF9, the researchers established that KLF9 plays a critical role in inducing PGR expression, and absence of KLF9 may lead to delayed parturition and late-term pregnancy. For further details regarding this study, please see our previous blog on reproductive cells.

Finally, keep in touch with us! Let us know how you are using Lifeline® cells in your lab and your study could be featured here on our blog.

Statistics from the American Cancer Society (www.cancer.org) and the American Congress of Obstetricians and Gynecologists (www.acog.org).

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