Mimicking mechanics in the ovary may offer key to infertility treatment

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According to the Centers for Disease Control and Prevention, about 6% of married women ages 15 to 44 in the U.S. are unable to get pregnant after one year of trying, the definition of infertility.

Conditions affecting a woman’s ovaries, fallopian tubes or uterus are the predominant causes of female infertility. New research by engineers at The Ohio State University is focused on ovarian problems, specifically when eggs cannot be released into the fallopian tubes.

A $1.4 million National Institutes of Health (NIH) grant will fund Biomedical Engineering Professor Shawn He’s work on a treatment for polycystic ovarian syndrome (PCOS) and premature ovarian failure (POF). PCOS is the most common cause of female infertility. He and his team will collaborate with Dr. Thomas Toth at Massachusetts General Hospital.

Ovarian follicles—which contain one oocyte surrounded by multiple follicular cells—are the fundamental functional tissue unit of the ovary. An oocyte in a primordial follicle is an immature ovum, or egg cell. In a healthy ovary, the primordial follicles continuously develop through several levels including primary, pre-antral, and antral toward egg maturity.

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Schematic illustration of (A) the mammalian ovary

In vitro culture of ovarian follicles to produce healthy fertilizable eggs is widely regarded as a promising solution to female infertility. However, none of the current follicle culture methods matches the mechanical environment of development of follicles in the ovaries.

Using a microfluidic device in the lab, He’s team fabricated a biomimetic ovarian microtissue with alginate hydrogel and collagen that closely resembles varying mechanical features within the ovary. Their mouse-based research results showed that mimicking an ovary’s mechanobiological features is essential in the gradual maturation of an egg cell up to the moment of ovulation. Moreover, their recent studies reveal that alginate hydrogel is exceptional in inhibiting ice formation to improve the survival of various stem cells after freezer storage.

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Shawn He in his Biomedical Research Tower lab
The NIH funding will allow He and Toth to build on the early success in the lab.

“Currently we have a success rate of 30%, of creating an implantable, fertilizable egg from a pre-antral stage ovarian follicle,” He said. “We think we can improve that to 90% for both pre-antral and primary follicles.”

He also has applied biomimetic stem cell research to other common maladies. His team recently invented a new stem cell therapy method for treatment of damage caused by heart attack. Their novel preparation of pluripotent stem cells for implantation into the heart is similar to how the female body prepares embryonic cells for implantation into the uterus wall during reproduction.

“I feel that any design by nature is the best design,” He added. “We have to learn from nature’s innovation.”