Approximately one in six female cancer survivors suffer from early menopause due to the serious side-effects of chemotherapy. Clinically known as premature ovarian insufficiency, this condition manifests as an inability of the ovaries to release eggs and the female sex hormone estrogen. Early menopause has long-term effects beyond fertility issues such as osteoporosis, low thyroid function, and increased risk of heart disease.

Scientists at Northwestern University, U.S., have worked on a possible solution to this probleman artificial ovary. Dr. Monica Laronda and her team at Northwestern University Feinberg School of Medicine have been working on developing an artificial ovary. In 2017, they implanted a functional 3-D printed artificial ovary in a sterile mouse that was then able to become pregnant and had live pups. Building on this groundbreaking work, Dr. Laronda and her team have taken a major step forward towards translating this technique for human use in the future. They have identified and mapped proteins in the pig ovary that form the scaffold for the different compartments within the ovary, similar to compartments found in the human ovary. Identifying and mapping these structural proteins are the first step towards developing a bio-ink or suitable biological material that can be used to 3-D print a bioprosthetic ovary for human use. The results of their latest work were recently published in Scientific Reports.

A major challenge in the field of bioprinting is the development of suitable biomaterials that can mimic the structure and functions of tissues and organs. This is especially true in the case of complex organs such as the ovaries that are comprised of different compartments with distinct functions. The human ovary is divided into two distinct compartments: the cortex that contains the immature follicles, which are maintained in a quiescent state, and the medulla that contains and supports the growing follicles. The ovarian follicle responds to molecular signals such as hormones as well as physical stress, to mature and eventually ovulate, releasing the single egg contained in the follicle.

It is hypothesized that the extracellular matrix plays a major role in the follicles remaining dormant or being activated into maturation. For instance, in mouse ovaries, physical compression of the primordial follicles in the cortex is necessary to maintain them in a quiescent state. Thus the work carried out by Dr. Laronda in identifying and mapping the structural proteins that make up the extracellular matrix is a key step towards being able to construct a functional artificial ovary for human use. As Dr. Laronda remarked in a recent press release, Our goal is to use the ovarian structural proteins to engineer a biological scaffold capable of supporting a bank of potential eggs and hormone-producing cells. Once implanted, the artificial ovary would respond to natural cues for ovulation, enabling pregnancy.

The technique developed by these researchers to process, identify, and map structural proteins in the extracellular matrix can be extended to study other organs and hence improve bioengineering methods involved in tissue regeneration or bioprinting. Dr. Laronda says, We have developed a pipeline for identifying and mapping scaffold proteins at the organ level. It is the first time that this has been accomplished and we hope it will spur further research into the microenvironment of other organs.

While there is a long way to go before we can print a functioning ovary for human use, the work presented in this report is a huge step forward for girls who undergo fertility-damaging cancer treatments.

Written by Bhavana Achary, Ph.D

References:

Henning, N.F., LeDuc, R.D., Even, K.A.et al.Proteomic analyses of decellularized porcine ovaries identified new matrisome proteins and spatial differences across and within ovarian compartments.Sci Rep9,20001 (2019). https://doi.org/10.1038/s41598-019-56454-3

Press release retrieved from https://www.eurekalert.org/pub_releases/2020-01/arh-st010620.php

Impact of premature ovarian insufficiency- https://www.nichd.nih.gov/health/topics/poi/conditioninfo/conditions

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Are we closer to being able to print a functioning artificial ovary? - Medical News Bulletin