ECE2022 Eposter Presentations Reproductive and Developmental Endocrinology (93 abstracts)
Developmental programming by maternal androgen excess is mediated by androgen receptor pathways
Haojiang Lu 1 , Congru Li 1 , Yu Pei 1 , Gustaw Eriksson 1 , Han-Pin Pui 1 , Sanjiv Risal 1 , Sara Torstensson 1 , Angelo Ascani 2 , Eva Lindgren 1 , Claes Ohlsson 3 , Anna Benrick 4 , 5 , Elisabet Stener-Victorin 1 & Qiaolin Deng 1
1Karolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden; 2Medizinische Universität Graz, Graz, Austria; 3University of Gothenburg, Department of Internal Medicine and Clinical Nutrition, Gothenburg, Sweden; 4University of Gothenburg, Department of Physiology, Gothenburg, Sweden; 5University of Skövde, School of Health and Education, Skövde, Sweden
Introduction: The hyperandrogenic in utero environment in pregnant women with polycystic ovary syndrome (PCOS) can affect embryo development and impair offspring health at adult age. Moreover, long term hyperandrogenic exposure also leads to unfavored changes to the mothers’ reproductive physiology, leading to miscarriage, preterm delivery, and perinatal mortality. The underlying mechanism(s) of pregnancy complications associated with PCOS and the consequence of hyperandrogenic intrauterine environment on the offspring is not well known.
Method: We used a PCOS-like mouse model induced by continuous exposure of dihydrotestosterone from prepuberty that develops obesity, anovulation and dysfunctional ovarian morphology, to study the effects of maternal hyperandrogenism during pregnancy. In addition, slight modifications are applied to the prepubertal PCOS-like mouse model to investigate critical periods in peri-pubertal life that projects to adverse pregnancy outcomes. To explore molecular mechanisms that contribute to the developmental defects, whole genome bisulfite and RNA sequencing of primordial germ cells and placenta were performed.
Results: Lower pregnancy rate and impaired placenta and embryonic development were found in the androgenised group, which was partially prevented by co-treatment with flutamide, an androgen receptor blocker. Moreover, germ cell specification was greatly compromised at embryonic day 10.5 and 13.5. The results of whole genome bisulfite sequencing and RNA sequencing of the primordial germ cells and placentas are currently under analysis. Furthermore, androgen exposure before the onset of vaginal opening may alter the physiology of uterus and vagina causing difficulty in labour.
Conclusion: Our results so far suggest that hyperandrogenism greatly compromise the PCOS-pregnancy and embryo development due to placenta dysfunction. Such effects are mainly mediated by the androgen receptor pathway as administration of flutamide partially prevents the compromised placenta and fetal development.
Article tools
My recent searches
My recently viewed abstracts
Authors
Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
© Bioscientifica 2024 |
Privacy policy |
Cookie settings
BiosciAbstracts
Bioscientifica Abstracts is the gateway to a series of products that provide a permanent, citable record of abstracts for biomedical and life science conferences.
Find out more