What is the cause of PMOS?

According to the 2020 study on Distinct Subtypes of PCOS with Novel Genetic Associations, there are specific genetic variations associated with each of the PMOS sub-types.

PMOS often runs in families with a 5x increased risk of having the condition if your biological mother has it.[1]  You have a 60-70% chance of having PMOS if your biological mother has PMOS[2] and a 50% chance if your biological sister has PMOS.[3]  In this article we explore the link between PMOS and Genetics.

The underlying cause of PMOS is a result of a complex interaction of genetic, epigenetic and environmental factors.[4]

Genetic factors relate to how an individual or a group of genes are implicated in health and disease.[5]  The genetic link underlying PMOS is far more complex than a single inherited gene and genetic factors explain less than 10% of PMOS heritability.[6]

Epigenetic factors relate to how genes are expressed or function in response to the environmental factors within the womb or later in life.[7]

Environmental factors include lifestyle, diet, stress, trauma and exposure to endocrine-disruptors,[8] natural or man-made chemicals that may mimic, block or interfere with the body’s hormones.[9]

There are more than 240 genetic variations and 29 genetic loci (specific regions of DNA) associated with PMOS.[10][11][12][13]  Certain groups of genes have been identified that influence some of the primary characteristics associated with PMOS, including:

• Androgen excess: DENND1A, CYP17A1 and SHBG contribute to elevated androgens and therefore lead to changes in appearance such as acne and hirsutism;[14][15]

• Hormonal regulation: FSHB, FSHR and LHCGR affect signaling of luteinizing hormone (LH) and follicle stimulating hormone (FSH) and therefore influence ovulation and menstrual cycles;[16][17]

• Ovarian function: AMH, ERBB4 and GATA4 regulate follicle maturation and ovarian reserve and therefore influence ovulation and fertility;[18][19]

• Ovarian aging: CHEK2 and RAD50 are believed to play a role in reproductive aging and egg quality and therefore influence fertility;[20]

• Metabolic dysfunction: THADA, FTO, INSR and HMGA2 are associated with insulin resistance, obesity and Type 2 diabetes;[21][22] and

• Inflammation: TOX3, YAP1 and MAPRE1 are linked to chronic inflammation.[23]

Sources

[1] https://www.nature.com/articles/s41591-019-0666-1

[2] https://www.cell.com/cell-metabolism/fulltext/S1550-4131(21)00004-8          

[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883751/

[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883751/

[5] https://www.cdc.gov/genomics/about/basics.htm

[6] https://academic.oup.com/jcem/article/98/12/4565/2833703

[7] https://www.cdc.gov/genomics/disease/epigenetics.htm

[8] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9864804/

[9] https://www.niehs.nih.gov/health/topics/agents/endocrine

[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7310679/

[11] https://www.sciencedirect.com/science/article/pii/S2590161319300948#bib0065

[12] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[13] https://www.nature.com/articles/ncomms9464

[14] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[15] https://pmc.ncbi.nlm.nih.gov/articles/PMC8775814/

[16] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[17] https://academic.oup.com/humupd/article-abstract/20/5/688/2952639?redirectedFrom=fulltext#google_vignette

[18] https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813

[19] https://www.nature.com/articles/ncomms9464

[20] https://www.fertstert.org/article/S0015-0282(17)30535-6/fulltext      

[21] https://www.nature.com/articles/ncomms9464

[22] https://pubmed.ncbi.nlm.nih.gov/21151128/

[23] https://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0035-1556568