Editing Polycystic ovary syndrome (section)

=== Stem cell models ===
[[Human embryonic stem cell]]s (hESCs) derived from the inner cell mass of blastocyst-stage embryos of women with PCOS have shown abnormal lipid metabolism, consistent with the pathophysiology of the disease.<ref name=":6">{{Cite journal |last1=Khatun |first1=Masuma |last2=Lundin |first2=Karolina |last3=Naillat |first3=Florence |last4=Loog |first4=Liisa |last5=Saarela |first5=Ulla |last6=Tuuri |first6=Timo |last7=Salumets |first7=Andres |last8=Piltonen |first8=Terhi T. |last9=Tapanainen |first9=Juha S. |date=January 2024 |title=Induced Pluripotent Stem Cells as a Possible Approach for Exploring the Pathophysiology of Polycystic Ovary Syndrome (PCOS) |journal=Stem Cell Reviews and Reports |language=en |volume=20 |issue=1 |pages=67–87 |doi=10.1007/s12015-023-10627-w |pmid=37768523 |pmc=10799779 |issn=2629-3269}}</ref> When the hESCs are differentiated into adipocytes, gene expression data from these fat cells reveal a downregulation or a decrease in genes linked to glucose, lipid, and steroid metabolism.<ref>{{Cite journal |last1=Li |first1=Peng-fen |last2=Wang |first2=Fang |last3=Kong |first3=Hui-juan |last4=Zhao |first4=Fang |last5=Bai |first5=Ai-hong |last6=Chen |first6=Xue-mei |last7=Sun |first7=Ying-pu |date=January 2012 |title=Establishment of polycystic ovary syndrome-derived human embryonic stem cell lines |url=http://www.tandfonline.com/doi/full/10.3109/09513590.2011.588748 |journal=Gynecological Endocrinology |language=en |volume=28 |issue=1 |pages=25–28 |doi=10.3109/09513590.2011.588748 |pmid=21780950 |issn=0951-3590}}</ref> Despite the significant findings provided by hESC research to understand the earliest stages of PCOS development, there are limitations in studying human embryos due to legal prohibitions and ethical concerns.

Recent studies have successfully developed in vitro PCOS disease models through [[Induced pluripotent stem cell]] technology (iPSC).<ref name=":6" /> Similar to hESCs, iPSC cells can be derived from patients and can differentiate into various cell types. Using adult somatic cells, iPSCs can reprogram the cells into a pluripotent state, which can then be specified to replicate PCOS-like traits. Furthermore, 3D “organoid” models of female reproductive tissue, such as the uterus and ovaries, produced from iPSCs, present a powerful way to stimulate the development of reproductive disorders such as PCOS in vitro.<ref name=":6" />
[[File:IPSC Model for PCOS.png|thumb|Induced pluripotent stem cell model for PCOS research]]

Although not widely utilized, some researchers have explored the use of this biotechnology to model PCOS. One study that characterized the link between obesity and PCOS reprogrammed PCOS-derived urine epithelial cells into adipocytes and found that iPSC lines had greater glucose consumption along with lower insulin response compared to controls.<ref>{{Cite journal |last1=Yang |first1=Sheng |last2=Ding |first2=Shufang |last3=Jiang |first3=Xianglong |last4=Sun |first4=Bolan |last5=Xu |first5=Qianhua |date=June 2016 |title=Establishment and adipocyte differentiation of polycystic ovary syndrome-derived induced pluripotent stem cells |journal=Cell Proliferation |language=en |volume=49 |issue=3 |pages=352–361 |doi=10.1111/cpr.12258 |pmid=27108524 |pmc=6496004 |issn=0960-7722}}</ref> These are results consistent with symptoms of the disease. Studies on iPSCs have also contributed significantly to understanding the behavior of ovarian [[granulosa cell]]s, which maintain follicular development and secrete steroid hormones.<ref>{{Cite journal |last1=Jozkowiak |first1=Malgorzata |last2=Piotrowska-Kempisty |first2=Hanna |last3=Kobylarek |first3=Dominik |last4=Gorska |first4=Natalia |last5=Mozdziak |first5=Paul |last6=Kempisty |first6=Bartosz |last7=Rachon |first7=Dominik |last8=Spaczynski |first8=Robert Z. |date=31 December 2022 |title=Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction |journal=Cells |language=en |volume=12 |issue=1 |pages=174 |doi=10.3390/cells12010174 |doi-access=free |pmid=36611967 |issn=2073-4409|pmc=9818374 }}</ref> The transcriptome data from the PCOS-derived iPSCs indicate dysfunctions in folliculogenesis and disruptions in the oocyte microenvironment.

Current growing data shows a strong association between mitochondrial malfunction and PCOS. iPSCs from PCOS patients have provided some evidence of impairments in glycolytic and mitochondrial functions.<ref name=":6" /> Interestingly, these cells exhibited a higher number of copies of mitochondrial DNA compared to the control. This may support the idea that mitochondrial biosynthesis is elevated in these patients as a compensatory response to the aberrations seen in the metabolic processes.<ref name=":6" />

iPSC models have great advantages over the ethical concerns in hESC research. One challenge to using this technology is controlling or assessing the intra-human variability, especially with a multifaceted disease such as PCOS. Nonetheless, these stem cell models are a valuable approach to gaining more insights into the disease.