Reproductive Profile of Neuronal Androgen Receptor Knockout Female Mice With a Low Dose of DHT

Author:

Ubba Vaibhave1,Joseph Serene1,Awe Olubusayo2,Jones Dustin2,Dsilva Milan K1,Feng Mingxiao3,Wang Junjiang34,Fu Xiaomin35,Akbar Razeen J1,Bodnar Brittany H1,Hu Wenhui1,Wang Hong1,Yang Xiaofeng1,Yang Ling6,Yang Peixin7,Taib Bouchra8,Ahima Rexford8,Divall Sara9,Wu Sheng13ORCID

Affiliation:

1. Center for Metabolic Disease Research, Temple University School of Medicine , Philadelphia, PA, 19140 , USA

2. Department of Cellular and Molecular Physiology, Johns Hopkins University School of Medicine , Baltimore, MD, 21287 , USA

3. Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD, 21087 , USA

4. Departments of Gastrointestinal Surgery and General Surgery, Guangdong Provincial People’s Hospital, Southern Medical University , Guangzhou, 510080 , China

5. Department of Endocrinology, The First Medical Center, Chinese PLA General Hospital , Beijing, 100853 , China

6. Department of Medical Genetics & Molecular Biochemistry, Temple University School of Medicine , Philadelphia, PA, 19140 , USA

7. Department of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine , Baltimore, 21201 , USA

8. Department of Medicine, Johns Hopkins University School of Medicine , Baltimore, MD, 21287 , USA

9. Department of Pediatrics, University of Washington, Seattle’s Children’s Hospital , Seattle, WA, 98145-5005 , USA

Abstract

Abstract Hyperandrogenism and polycystic ovarian syndrome result from the imbalance or increase of androgen levels in females. Androgen receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron-specific AR knockout (KO) mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone, and estradiol were comparable between the control and the SynARKO mice. There were no differences in cyclicity and fertility between the control and SynARKO mice, with similar impairment in both groups on DHT treatment. Neuronal AR KO, as in this SynARKO mouse model, did not alleviate the infertility associated with DHT treatment. These studies suggest that neuronal AR KO neither altered reproductive function under physiological androgen levels, nor restored fertility under hyperandrogenic conditions.

Funder

National Institutes of Health

Publisher

The Endocrine Society

Subject

Endocrinology

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