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ARTIFICIAL OVARIES
Activity Packet
Carnegie Mellon University - Department of Biomedical Engineering
Note : This educational resource was developed as a project by the Carnegie Mellon student Meghan McGraw for the summer 2020 course, Experiential Learning through Projects [99-520], inspired by a project completed by student Carolyn Bolz in the spring of 2020. Editing and additional project development was also completed by Claire Kenny.
Background
Making artificial ovaries is a relatively new (~2015 - present) technology that is still in animal trials. The creation of artificial ovaries aims to restore or create fertility in those who are infertile, as well as balance hormones. It has been tested in mice, where some were able to ovulate and produce viable offspring, showing promise for being able to be used in humans in the future, although some major issues remain in making them accessible for human use (“Researchers Create”).
Students will learn how to think like engineers--they will be able to identify a problem (ovarian pathophysiology and infertility) and explore viable solutions (tissue engineering and artificial ovaries) to it based on constraints (ovarian anatomy and physiology). It is recommended for a high school audience with general biology knowledge (anatomy and physiology is also useful, but not required).
There are three activities included--a lecture, a sugar crystal biomaterials activity, and an interactive ovarian histology lab. While doing all three provides students with the most complete knowledge of the field, they can be done separately. From the lecture students will gain a ‘bird’s eye view’ of all aspects of creating an artificial ovary. The sugar crystal activity will allow students to make a familiar craft with an analogy to the components of tissue engineering. An optional competition to see who can grow the largest sugar crystals can be held and related back to the process of trying to successfully grow cells on scaffolds. The ovarian histology lab allows students to examine normal functioning ovarian tissue, as well as diseased tissue that requires engineering interventions. Supplemental worksheets for the sugar crystals and histology lab as well as vocab quizzes are also included.
Objectives
After these activities, students should be able to:
Lecture
Demonstrate knowledge of basic ovarian anatomy and physiology o Name stages of the ovarian cycle Name and describe conditions that cause ovarian damage Identify the stages of tissue engineering o Name each component of an artificial ovary and describe how each serve to help solve infertility problems Discuss who can benefit from artificial ovaries Discuss the ethical questions that go into consideration with new technology
Sugar Crystal Biomaterials
Name the components required to make an artificial ovary and briefly describe their purpose Compare and contrast sugar crystal making to growing cells
Interactive Ovarian Histology Lab
Define histology and explain why it is useful for understanding ovarian anatomy Name, define, and draw stages of the ovarian cycle Name conditions that affect ovarian tissue and describe some of the histological characteristics of the conditions
Materials
Lecture
Projector A computer able to display PowerPoint slides
Sugar Crystal Biomaterials
*Note: The following resources are enough for 16 individual students. This can be done in teams to save resources. *
24 cups of sugar (with extra sugar for seeding) 8 cups of water 16 pipe cleaners 16 pencils Tape 16 cups (Note: glass cups or Mason Jars are best. However, plastic cups may be substituted)
Vocabulary
Note: The following are terms students may be unfamiliar with. They are not required to know all of them. Depending on the classroom environment, it is the educator’s decision on how many terms that the students should know. The definitions were drawn from the sources named at the end of this packet.
Lecture and Kahoot
- Biocompatibility - the property of a material being compatible with tissue Bioreactor- a chamber for cells to grow in
- Chemotherapy - a drug treatment with chemicals to kill fast-growing cells
- Decellularization - stripping the cells off of the extracellular matrix (ECM)
- Endometriosis - a condition where uterine tissue grows outside the uterus
- Estrogen - signals the buildup on the uterine lining; a surge in this leads to ovulation
- Fertility - the ability to produce offspring
- Fertilization - union of a sperm and an egg
- Follicle - an ovum and the cells around it
- Menstrual Cycle - the process of ovulation and menstruation; broken into three phases
- Oocyte - the cell that develops into an egg
- Ovaries - a female reproductive organ that is responsible for producing and releasing eggs, estrogen, and progesterone
- Ovulation - the release of an egg from the ovary
- Ovum - a mature egg
- Polycystic Ovary Syndrome (PCOS) - a condition where follicular growth is arrested and the developing follicle turns into a large fibrotic ‘cyst’
- Progesterone - a hormone released by the ovary (corpus luteum) that maintains the uterine lining in preparation for fertilization
- Radiation - using high energy waves to kill cancer cells
- Reproductive system - all organs involved in sexual reproduction
- Scaffold - a structures where cells can grow
- Tissue Engineering - combining scaffolds, cells, and other biologically active molecules into functional tissues
Extra:
- Androgens - male hormones
- Corpus Luteum - the remainder of the follicle structure--maintains high progesterone levels
- Cortex - the area of the ovaries that contains follicles and connective tissue
- Endocrine system - organs and glands that make hormones
- Epithelial cells - cells that cover tissue
- Follicle-Stimulating Hormone (FSH) - helps stimulate the growth of eggs
- Follicular Phase - the phase in which the follicle matures before ovulation
- Integrins-proteins on a cell that attach it to the environment
- Luteal Phase - the phase in which the corpus luteum maintains the uterine lining in preparation for pregnancy
- Luteinizing Hormone (LH) - a surge in this hormone triggers ovulation
- Medulla - in the center of the ovary
- Oogenesis - the development of eggs into viable gametes that are fertilizable
- Pituitary - an endocrine gland responsible for secreting hormones
Sugar Crystal Biomaterials
- Biocompatibility- the property of a material being compatible with tissue
- Bioreactor- a chamber for cells to grow in
- Decellularization- stripping the cells off of the extracellular matrix (ECM)
- Oocyte- the cell that develops into an egg
- Scaffold- a structures where cells can grow
Virtual Histology Lab
- Corpus Albicans - the stage where the corpus luteum is degrading after LH levels fall
- Corpus Luteum - the remainder of the follicle structure--maintains high progesterone levels
- Endometriosis - a condition where uterine tissue grows outside
- Granulosa Lutein cells - in the corpus luteum, these cells surround a blood clot located where the egg was previously located
- Lipid - fat
- Luteinized - process of lipid accumulation and formation of the corpus luteum
- Luteinizing Hormone (LH) - a surge in this hormone triggers ovulation
- Metastasize - a tumor spreading to other parts of the body
- Radiation - using high energy waves to kill cancer cells
- Squamous - flat cells
- Stroma - the supportive tissue of an organ
- Theca cells - produce androgens
- Tumor - abnormal cell grow (neoplasm)
- Vascularization - the presence of blood vessels
- Zona pellucida - recognition coating for sperm cells
Procedure
Lecture
Note: The lecture can be distributed to students for independent remote learning.
- Review the PowerPoint slides and slide guide to become familiar with the terms and topics used in the slides.
- Present a lecture to students using the PowerPoint slides. They are welcome to (and should be encouraged to) take notes.
Sugar Crystals Biomaterials
Note: This activity can be done remotely if students have access to the materials and a parent is available to help them.
- Print out the supplemental worksheet for students from the website, listed under Sugar Crystals Biomaterials.
- Gather materials. The instructor should give the cups/Mason jars, pencils, Sharpies, and pipe cleaners to the students.
- Bring water to a boil in the saucepan.
- Pour sugared water into each cup, almost filling to the top.
- Cover the top of each cup with a paper towel.
- Wait 3-5 days to take the pipe cleaners out of the water.
- After leaving the sugar crystals to set, give students the worksheet and let them match the components of tissue engineering to those of sugar crystals.
Optional:
- Conclude with the discussion questions, listed on the website under Additional Resources.
- After letting the sugar crystals set, take them out and let them dry for a few
minutes.
- Place weighing paper on a scale, and tare the scale.
- Weigh each person’s or team’s sugar crystals, using and taring new piece of weighing paper each time. Have the students record the weight on their worksheet. A winner (or winners) can be declared by seeing which sugar crystals grew the largest. A prize can be distributed to the winner(s).
Interactive Ovarian Histology Lab Note: This activity can be done remotely.
- Print out the supplemental worksheets
- Open the Virtual Histology Lab PowerPoint
- Go through the “How to Play” instructions with the students
- Let students complete the activity
- Students can turn in the worksheet for grading
Additional Resources
- Ovarian Histology -- An article showing and explaining every stage of the ovarian cycle. Histology@Yale. medcell.med.yale.edu/histology/ovary_follicle.php.
- Detailed Ovarian Anatomy -- An article providing information on female reproductive anatomy. Sokol, E. “ Clinical Anatomy of the Uterus, Fallopian Tubes, and Ovaries.” Glowm, July 2010, https://www.glowm.com/section_view/heading/Clinical+Anatomy+of+the+Uterus,+ Fallopian+Tubes,+and+Ovaries/item/
- Infertility -- An article listing causes of female infertility. “What Causes Female Infertility?.” https://web.stanford.edu/class/siw198q/websites/reprotech/New%20Ways%20of%20Maki ng%20Babies/Causefem.htm
- Menstrual Cycle -- Articles going through the phases of the menstrual cycle. Wakim, S. and Grewal, M. ‘22.7: Menstrual Cycle.’ Biology LibreTexts , Libretexts, 16 June 2020, https://bio.libretexts.org/Bookshelves/Human_Biology/Book:Human_Biology (Wakim_and_Grewal)/22: Reproductive_System/22.07:_Menstrual_Cycle
Watson, S. ‘Stages of Menstrual Cycle.” Healthline, 23 October 2010, https://www.healthline.com/health/womens-health/stages-of-menstrual-cycle
- Endometriosis -- An article explaining every aspect of endometriosis.
- The Patent for Artificial Ovaries--The current patent for artificial ovaries. “US10479980B2 – Artificial ovary. https://patents.google.com/patent/US10479980B2/en
Next Generations Science Standards Alignment
HS-ETS1-1. Analyze a major global challenge to specify qualitative and quantitative criteria and constraints for solutions that account for societal needs and wants.
HS-ETS1-2. Design a solution to a complex real-world problem by breaking it down into smaller, more manageable problems that can be solved through engineering.
Authors
Lesson idea from Carolyn Botz, final product developed by Meghan McGraw as a project for 99-520O Development of Biomedical Engineering Educational Outreach Activities for Middle and High School Audiences
Sources
AFIP. “Outer Cortex Is Collagenized with Several Follicle Cysts Arrayed beneath It.” Polycystic Ovary Disease , Pathology Outlines, 2012, www.pathologyoutlines.com/topic/ovaryPCO.html.
Baier, A. “Nano-delivered Therapy Inhibits Spread of Ovarian, Uterine Cancer Cells.” USF Health, 24 July 2019. https://hscweb3.hsc.usf.edu/blog/2019/07/24/ nano- delivered-therapy-inhibits-spread-of-ovarian-uterine-cancer-cells/
“Cardiac Surgery Operating Room.” Surgery , Wikipedia, 2014,https://upload.wikimedia.org /wikipedia/commons/2/2e/Cardiac_surgery_operating_room.jpg Dictionary.com , www.dictionary.com/.
Dolmans, M. and Amorim, C. “FERTILITY PRESERVATION:Construction and use of artificial ovaries” Reproduction , BioScientifica, 12 November 2019, https://rep.bioscientifica.com/view/journals/rep/158/5/REP-18-0536.xml Garcia, Alexandra. “Oogenesis Labeled.” Ovary , Wikipedia, 2020, https://en.wikipedia.org/wiki/File:Oogenesis_Labeled.svg
Gleadall, A. et al. “Figure 6.” Review of additive manufactured tissue engineering scaffolds: relationship between geometry and performance , Burns and Trauma, 3 July 2018, https://burnstrauma.biomedcentral.com/articles/10.1186/s41038-018-0121- 4#Fig
“Filter.” Wikimedia, https://upload.wikimedia.org/wikipedia/commons/thumb/3/37/Filter.svg/ 1016px-Filter.svg.png Han, L. and Garcia, R. “Endometriosis.” Pathology Outlines, 16 March 2020,
http://www.pathologyoutlines.com/topic/uterusendometriosis.ht ml
Hill, Mark. “Monkey- Ovary Primordial Follicle.” Ovary Development , Embryology, 2010, embryology.med.unsw.edu.au/embryology/index.php/Ovary_Development. Hill, Mark. “Ova44he.” Ovary Development , Embrology, 2010, embryology.med.unsw.edu.au/embryology/index.php/Ovary_Development. Histology@Yale. medcell.med.yale.edu/histology/ovary_follicle.php.
“How Cancer and Cancer Treatment Can Affect Fertility in Females.” American Cancer Society, 6 February 2020. https://www.cancer.org/treatment/ treatments-and- side-effects/physical-side-effects/fertility-and-sexual-side-effects/ fertility-and- women-with-cancer/How-cancer-treatments-affect-fertility.html Human Eggs , www.sizes.com/people/eggs.htm. Keeffe, Jillian. “What Are Tissue Engineering Scaffolds?” Wisegeek , 2020, www.wisegeek.net/what-are-tissue-engineering-scaffolds.htm. Kershner, Kate. “Why Do We Experiment on Mice?” HowStuffWorks Science , HowStuffWorks, 30 June 2020, science.howstuffworks.com/innovation/scientific- experiments/experiment-on-mice.htm. Kim, J., Perez, A., Claflin, J., David, A., Zhou, H., and Shikanov, A. “Synthetic hydrogel supports the function and regeneration of artificial ovarian tissue in mice.” Nature, 7 July 2016, https://www.nature.com/articles/npjregenmed Laronda, M., et al.“Follicles Attached to Corners of Pores in Filament Scaffolds.” A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice , PubMed, 16 May 2017, https://pubmed.ncbi.nlm.nih.gov/28509899/
Meirow, D., et al. “Cortical Fibrosis and Blood-Vessels Damage in Human Ovaries Exposed to Chemotherapy.” Cortical Fibrosis and Blood-Vessels Damage in Human Ovaries Exposed to Chemotherapy. Potential Mechanisms of Ovarian Injury , Research Gate, 2007, www.researchgate.net/publication/6481366_Cortical_fibrosis_and_ blood- vessels_damage_in_human_ovaries_exposed_to_chemotherapy_potential_mechani sms_of_ovarian_injury.
“Micrograph of Endometriosis of the Ovary.” Endometriosis , Libre Pathology, 2010, librepathology.org/wiki/Endometriosis.
“Microscope.” PNG All , 2016, www.pngall.com/microscope-png/download/15108. “Mouse implanted with ovaries made by 3D printer gives birth, offering new hope for infertile women.” National Post, 18 May 2017, https://nationalpost.com/health/mouse-implanted-with-ovaries-made-by-3d- printer -gives-birth-offering-new-hope-for-infertile-women/ Mrabet, J. “Bioreactor Principle.” Bioreactor , Wikipedia, 2009, https://en.wikipedia.org/wiki/Bioreactor#/media/File:Bioreactor_principle.svg “Mucinous Lmp Ovarian Tumour Intermed Mag.” Ovarian Cancer , Wikipedia, 2009, en.wikipedia.org/wiki/Ovarian_cancer. Mullin, E. “Bioengineered Ovaries Can Survive in Mice. Humans Are Next.” Medium, 20 September 2018. https://medium.com/neodotlife/artificial-ovaries- f84ecc7beb6a
