Having a reduced amount of HDAC3 renders mice sterile
A missing protein may help explain why some women with endometriosis are infertile.
In samples of lining from the uterus, infertile women with the disorder had lower amounts of a protein called histone deacetylase 3, or HDAC3, than fertile women without endometriosis, a study finds. When mice were engineered to have a decreased amount of HDAC3 in the uterus, the animals became sterile, researchers report online January 9 in Science Translational Medicine.
The new work brings scientists a step closer to understanding what’s driving infertility in women with endometriosis, says Linda Giudice, a reproductive endocrinologist at the University of California, San Francisco who was not involved in the study. Such research could potentially offer ways to improve these women’s ability to become pregnant, she says.
Endometriosis — a disorder in which tissue from the lining of the uterus invades other parts of the body, such as the ovaries, lining of the pelvis and bowels — can cause severe pain and infertility. Researchers don’t know why endometriosis strikes. Women whose menstruation began before age 10, were of low birth weight or were exposed to a synthetic estrogen called diethylstilbestrol, or DES, in the womb are at an increased risk for the disorder. Having family members with the disease also puts one at risk.
The disorder is estimated to affect up to 10 percent of women of childbearing age. Among women with infertility, the prevalence of the condition may be as high as 50 percent. Reproductive biologist Jae-Wook Jeong at Michigan State University in Grand Rapids and colleagues wanted to study why fertility may be reduced during endometriosis.
In mice with a protein called HDAC3 (left), the embryo (arrow) was able to successfully attach to the lining of the uterus. But in mice lacking HDAC3 (right), the embryo (arrow) couldn’t connect with the lining.
In the new work, Jeong and his colleagues demonstrated that mice with sufficient amounts of HDAC3 — which plays a role in increasing or decreasing other genes’ activity — remained fertile. In these mice, the uterus was able to receive an embryo, which nestles into the organ’s tissue for protection and nourishment during development. But in mice lacking the protein, the uterus and embryo don’t connect. The embryo drifts unmoored in the empty space within the organ, making pregnancy impossible.
The loss of the protein didn’t just keep the uterus from being receptive to an embryo. The researchers also found that mice lacking HDAC3 had more collagen, a structural protein, in the uterus. Collagen is a component of abnormal, fibrous areas that develop in endometriosis. Learning more about HDAC3’s role in how the fibrous areas arise, Jeong says, may lead to new treatments for the disease.
T.H. Kim et al. Loss of HDAC3 results in nonreceptive endometrium and female infertility. Science Translational Medicine. Published online January 9, 2019. doi:10.1126/scitranslmed.aaf7533.
G. Marino. Protein missing in endometriosis cases. Science News. Vol. 146, August 20, 1994, p. 118.