miércoles, 15 de julio de 2020

DNA changes linked to endometriosis | National Institutes of Health (NIH)

DNA changes linked to endometriosis

At a Glance

Researchers found changes to DNA in the uterine cells of women with endometriosis that weren’t seen in women without the condition.
The results suggest a new strategy for diagnosing endometriosis and its severity.

Currently, a diagnosis of endometriosis can only be made using a surgical procedure. sturti / E+ via Getty Images

In endometriosis, tissue similar to that in the lining of the uterus grows in other places in the body. It may grow in the ovaries, fallopian tubes, bowels, or bladder. Endometriosis affects 5 to 10% of women in the United States. The main symptoms are pain, especially during menstrual periods, and infertility.

The lining of the uterus, or endometrium, undergoes changes in response to two hormones: estrogen and progesterone. These hormones cause changes in gene expression, or activity, that help prepare the uterus for pregnancy. But with endometriosis, abnormal responses to progesterone are thought to cause inflammation of the uterine lining. This inflammation makes pregnancy more difficult. Researchers aren’t sure exactly what causes endometriosis, but many factors likely underlie its development, including hormones, genes, and other influences.

To better understand how cells in the uterus respond to these two hormones, a research team led by Drs. Sahar Houshdaran and Linda C. Giudice at the University of California, San Francisco examined endometrial stromal fibroblast cells, which regulate cells in the lining of the uterus. They compared cells from women with stage I (minimal) and stage IV (severe) endometriosis as well as those without the condition. The work was funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Results appeared on June 17, 2020 in Plos Genetics.

The researchers exposed the cells to four different hormonal conditions for two weeks. These included a control condition, estradiol (a type of estrogen) alone, progesterone alone, and a combination of the two hormones. The hormone levels mimicked the changes that normally occur during the menstrual cycle. The team analyzed a chemical modification in the cells called DNA methylation. While DNA methylation doesn’t affect the genetic sequence, it can change gene expression.

The regions of DNA that were methylated were different for endometrial cells in stage I and stage IV. The cells also showed different patterns of gene expression. These findings suggest there may be two distinct subtypes of endometriosis, rather than different degrees of the condition.

The cells also showed distinct DNA methylation and gene expression patterns for each of the hormone conditions. Cells from women with endometriosis showed abnormal genetic responses to both progesterone and estrogen.

“The data indicate that the proper interactions of hormones and DNA methylation are critical in normal uterine function,” Houshdaran says. “The changes in these interactions that we’ve seen could play a role in the infertility that often accompanies endometriosis.”

“The findings raise the possibility that differences in methylation patterns could one day be used to diagnose endometriosis and develop customized treatment plans for patients,” explains Dr. Stuart B. Moss of NICHD. Currently, the only definitive way to diagnose endometriosis is with a surgical procedure called a laparoscopy.

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miércoles, 15 de julio de 2020