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Dissecting the Impact of Maternal Androgen Exposure on Developmental Programming through Targeting the Androgen Receptor

Lu, Haojiang (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Jiang, Hong (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Li, Congru (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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Derisoud, Emilie (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Zhao, Allan (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Eriksson, Gustaw (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Lindgren, Eva (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Pui, Han‐Pin (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Risal, Sanjiv (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Pei, Yu (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Maxian, Theresa (författare)
Department of Obstetrics and Gynaecology Reproductive Biology Unit, Placental Development Group, Medical University of Vienna, Austria
Ohlsson, Claes (författare)
Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sweden
Benrick, Anna, 1979- (författare)
Högskolan i Skövde,Institutionen för hälsovetenskaper,Forskningsmiljön hälsa, hållbarhet och digitalisering,Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden,Translationell medicin TRIM, Translational Medicine TRIM
Haider, Sandra (författare)
Department of Obstetrics and Gynaecology, Reproductive Biology Unit, Placental Development Group, Medical University of Vienna, Austria
Stener‐Victorin, Elisabet (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Deng, Qiaolin (författare)
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
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 (creator_code:org_t)
2024
2024
Engelska.
Ingår i: Advanced Science. - : John Wiley & Sons. - 2198-3844.
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Women with polycystic ovary syndrome (PCOS) exhibit sustained elevation incirculating androgens during pregnancy, an independent risk factor linked topregnancy complications and adverse outcomes in offspring. Yet, furtherstudies are required to understand the effects of elevated androgens on celltype-specific placental dysfunction and fetal development. Therefore, aPCOS-like mouse model induced by continuous androgen exposure isexamined. The PCOS-mice exhibited impaired placental and embryonicdevelopment, resulting in mid-gestation lethality. Co-treatment with theandrogen receptor blocker, flutamide, prevents these phenotypes includinggerm cell specification . Comprehensive profiling of the placenta bywhole-genome bisulfite and RNA sequencing shows a reduced proportion oftrophoblast precursors, possibly due to the downregulation of Cdx2expression. Reduced expression of Gcm1, Synb, and Prl3b1 is associated withreduced syncytiotrophoblasts and sinusoidal trophoblast giant cells, impairsplacental labyrinth formation. Importantly, human trophoblast organoidsexposed to androgens exhibit analogous changes, showing impairedtrophoblast differentiation as a key feature in PCOS-related pregnancycomplications. These findings provide new insights into the potential cellulartargets for future treatments.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Reproduktionsmedicin och gynekologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Obstetrics, Gynaecology and Reproductive Medicine (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

developmental programming
human trophoblast organoids
placental development
polycystic ovary syndrome
Translationell medicin TRIM
Translational Medicine TRIM

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