Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Elevated prenatal anti-Mullerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood
Jean Pierre Aubert Res Ctr JPArc, Lab Dev & Plast Neuroendocrine Brain, Inserm, UMR S 1172, Lille, France;Univ Lille, FHU Days Hlth 1000, Lille, France.
Jean Pierre Aubert Res Ctr JPArc, Lab Dev & Plast Neuroendocrine Brain, Inserm, UMR S 1172, Lille, France;Univ Lille, FHU Days Hlth 1000, Lille, France.
Jean Pierre Aubert Res Ctr JPArc, Lab Dev & Plast Neuroendocrine Brain, Inserm, UMR S 1172, Lille, France;CHU Lille, Inst Biol Reprod Spermiol CECOS, Lille, France.
Jean Pierre Aubert Res Ctr JPArc, Lab Dev & Plast Neuroendocrine Brain, Inserm, UMR S 1172, Lille, France;Univ Lille, FHU Days Hlth 1000, Lille, France.
Show others and affiliations
2018 (English)In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 24, no 6, p. 834-846Article in journal (Refereed) Published
Abstract [en]

Polycystic ovary syndrome (PCOS) is the main cause of female infertility worldwide and corresponds with a high degree of comorbidities and economic burden. How PCOS is passed on from one generation to the next is not clear, but it may be a developmental condition. Most women with PCOS exhibit higher levels of circulating luteinizing hormone, suggestive of heightened gonadotropin-releasing hormone (GnRH) release, and anti-Mullerian hormone (AMH) as compared to healthy women. Excess AMH in utero may affect the development of the female fetus. However, as AMH levels drop during pregnancy in women with normal fertility, it was unclear whether their levels were also elevated in pregnant women with PCOS. Here we measured AMH in a cohort of pregnant women with PCOS and control pregnant women and found that AMH is significantly more elevated in the former group versus the latter. To determine whether the elevation of AMH during pregnancy in women with PCOS is a bystander effect or a driver of the condition in the offspring, we modeled our clinical findings by treating pregnant mice with AMH and followed the neuroendocrine phenotype of their female progeny postnatally. This treatment resulted in maternal neuroendocrine-driven testosterone excess and diminished placental metabolism of testosterone to estradiol, resulting in a masculinization of the exposed female fetus and a PCOS-like reproductive and neuroendocrine phenotype in adulthood. We found that the affected females had persistently hyperactivated GnRH neurons and that GnRH antagonist treatment in the adult female offspring restored their neuroendocrine phenotype to a normal state. These findings highlight a critical role for excess prenatal AMH exposure and subsequent aberrant GnRH receptor signaling in the neuroendocrine dysfunctions of PCOS, while offering a new potential therapeutic avenue to treat the condition during adulthood.

Place, publisher, year, edition, pages
2018. Vol. 24, no 6, p. 834-846
National Category
Obstetrics, Gynecology and Reproductive Medicine
Identifiers
URN: urn:nbn:se:uu:diva-357700DOI: 10.1038/s41591-018-0035-5ISI: 000434281300028PubMedID: 29760445OAI: oai:DiVA.org:uu-357700DiVA, id: diva2:1240561
Funder
EU, Horizon 2020, 725149/REPRODAMHEU, Horizon 2020, H2020-MSCA-IF-2014Available from: 2018-08-21 Created: 2018-08-21 Last updated: 2018-08-21Bibliographically approved

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Dewailly, DidierSundström Poromaa, IngerPrevot, Vincent
By organisation
Reproductive Health
In the same journal
Nature Medicine
Obstetrics, Gynecology and Reproductive Medicine

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 35 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf