Editing Polycystic ovary syndrome (section)

=== Environment ===
PCOS may be related to or worsened by exposures{{clarify|reason=Exposures to what?|date=November 2022}} during the [[Pregnancy|prenatal period]],<ref name="Hoeger-2014">{{cite journal | vauthors = Hoeger KM | title = Developmental origins and future fate in PCOS | journal = Seminars in Reproductive Medicine | volume = 32 | issue = 3 | pages = 157–8 | date = May 2014 | pmid = 24715509 | doi = 10.1055/s-0034-1371086 | s2cid = 32069697 }}</ref><ref name="Abbott-2005">{{cite journal | vauthors = Abbott DH, Barnett DK, Bruns CM, Dumesic DA | title = Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? | journal = Human Reproduction Update | volume = 11 | issue = 4 | pages = 357–374 |date= 2005 | pmid = 15941725 | doi = 10.1093/humupd/dmi013 | doi-access = free }}</ref><ref name="Rasgon-2004">{{cite journal | vauthors = Rasgon N | title = The relationship between polycystic ovary syndrome and antiepileptic drugs: a review of the evidence | journal = Journal of Clinical Psychopharmacology | volume = 24 | issue = 3 | pages = 322–334 | date = June 2004 | pmid = 15118487 | doi = 10.1097/01.jcp.0000125745.60149.c6 | s2cid = 24603227 }}</ref> [[epigenetic]] factors, environmental impacts (especially industrial endocrine disruptors, such as [[bisphenol A]] and certain drugs)<ref name="Rutkowska-2014">{{cite journal | vauthors = Rutkowska A, Rachoń D | title = Bisphenol A (BPA) and its potential role in the pathogenesis of the polycystic ovary syndrome (PCOS) | journal = Gynecological Endocrinology | volume = 30 | issue = 4 | pages = 260–5 | date = April 2014 | pmid = 24397396 | doi = 10.3109/09513590.2013.871517 | s2cid = 5828672 }}</ref><ref name="Palioura-2013">{{cite journal | vauthors = Palioura E, Diamanti-Kandarakis E | title = Industrial endocrine disruptors and polycystic ovary syndrome | journal = Journal of Endocrinological Investigation | volume = 36 | issue = 11 | pages = 1105–11 | date = December 2013 | pmid = 24445124 | doi = 10.1007/bf03346762 | s2cid = 27141519 }}</ref><ref name="Hu-2011">{{cite journal | vauthors = Hu X, Wang J, Dong W, Fang Q, Hu L, Liu C | title = A meta-analysis of polycystic ovary syndrome in women taking valproate for epilepsy | journal = Epilepsy Research | volume = 97 | issue = 1–2 | pages = 73–82 | date = November 2011 | pmid = 21820873 | doi = 10.1016/j.eplepsyres.2011.07.006 | s2cid = 26422134 }}</ref> and the increasing rates of obesity.<ref name="Palioura-2013" />

[[Endocrine disruptor]]s are defined as chemicals that can interfere with the [[endocrine system]] by mimicking hormones such as [[estrogen]]. According to the [[National Institutes of Health|NIH (National Institute of Health)]], examples of endocrine disruptors can include [[dioxins]] and [[triclosan]]. Endocrine disruptors can cause adverse health impacts in animals.<ref>{{Cite web |title=Endocrine Disruptors |url=https://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm |access-date=10 November 2022 |website=National Institute of Environmental Health Sciences |language=en |archive-date=11 June 2020 |archive-url=https://web.archive.org/web/20200611191841/https://www.niehs.nih.gov/health/topics/agents/endocrine/index.cfm |url-status=live }}</ref> Additional research is needed to assess the role that endocrine disruptors may play in disrupting reproductive health in women and possibly triggering or exacerbating PCOS and its related symptoms.<ref>{{cite journal | vauthors = Merkin SS, Phy JL, Sites CK, Yang D | title = Environmental determinants of polycystic ovary syndrome | journal = Fertility and Sterility | volume = 106 | issue = 1 | pages = 16–24 | date = July 2016 | pmid = 27240194 | doi = 10.1016/j.fertnstert.2016.05.011 | doi-access = free }}</ref>

The study of epigenetic changes in PCOS in utero or after birth has become an emerging area of research. While extensive research is not currently available, some studies are looking into the connection between abnormal DNA methylation changes in various tissues and the development of PCOS.<ref name=":4">{{Cite journal |last1=Liu |first1=Yan-Nan |last2=Qin |first2=Yi |last3=Wu |first3=Bin |last4=Peng |first4=Hui |last5=Li |first5=Ming |last6=Luo |first6=Hai |last7=Liu |first7=Lin- Lin |date=August 2022 |title=DNA methylation in polycystic ovary syndrome: Emerging evidence and challenges |url=https://linkinghub.elsevier.com/retrieve/pii/S0890623822000594 |journal=Reproductive Toxicology |language=en |volume=111 |pages=11–19 |doi=10.1016/j.reprotox.2022.04.010|pmid=35562068 |bibcode=2022RepTx.111...11L |doi-access=free }}</ref>  Environmental exposure to endocrine disruptors such as phthalates could alter DNA methylation patterns, particularly in the ovaries, granulosa cells, and adipose tissue.<ref name=":4" />

One study observed early embryonic development of mice subjected to di--(2-ethylhexyl) phthalate (DEHP) and the results showed abnormal methylation patterns in the Stra8 gene involved in meiosis initiation.<ref name=":5">{{Cite journal |last1=Zhang |first1=Teng |last2=Li |first2=Lan |last3=Qin |first3=Xun-Si |last4=Zhou |first4=Yang |last5=Zhang |first5=Xi-Feng |last6=Wang |first6=Lin-Qing |last7=De Felici |first7=Massimo |last8=Chen |first8=Hong |last9=Qin |first9=Guo-Qing |last10=Shen |first10=Wei |date=May 2014 |title=Di-(2-ethylhexyl) phthalate and bisphenol A exposure impairs mouse primordial follicle assembly in vitro |url=https://onlinelibrary.wiley.com/doi/10.1002/em.21847 |journal=Environmental and Molecular Mutagenesis |language=en |volume=55 |issue=4 |pages=343–353 |doi=10.1002/em.21847 |pmid=24458533 |bibcode=2014EnvMM..55..343Z |issn=0893-6692}}</ref> The gene for transcription factor Lhx8, involved in early follicular changes, was also impacted by DEHP when the neonatal mouse ovaries were analyzed. Together, these results showed DEHP induced epigenetic changes via DNA methylation to interfere with folliculogenesis, symptomatic of PCOS.<ref name=":5" /> Although DNA methylation in human embryonic development is not fully characterized, the animal model studies on epigenetic changes provide information to suggest that PCOS may have fetal origins.

Androgen excess is a central feature in the PCOS phenotype, and exposure in utero has shown PCOS-like features in adulthood. A study from 2014 induced DNA hypomethylation in the ovarian tissue of zebrafish exposed to androgens early in development.<ref name="ReferenceA">{{Cite journal |last1=Xu |first1=Ning |last2=Chua |first2=Angela K. |last3=Jiang |first3=Hong |last4=Liu |first4=Ning-Ai |last5=Goodarzi |first5=Mark O. |date=1 August 2014 |title=Early Embryonic Androgen Exposure Induces Transgenerational Epigenetic and Metabolic Changes |journal=Molecular Endocrinology |language=en |volume=28 |issue=8 |pages=1329–1336 |doi=10.1210/me.2014-1042 |pmid=24992182 |pmc=5414805 |issn=0888-8809}}</ref> Glucose homeostasis alterations were also observed. Furthermore, these effects were carried into the next generation, suggesting that epigenetic changes caused by excess androgens in the fetus could be transgenerational.<ref name="ReferenceA"/>