Bone strength is reduced in a neonatal androgenized rat model

Lady Katerine Serrano Mujica; Carolina Dos Santos Amaral; Fernanda Soldatelli Valente; Ligia Gomes Miyazato; Soraia Macari; Tarcília Aparecida da Silva; Breno Rocha Barrioni; Bruna Leonel Carlos; Guilherme Jafroni Alves Silva; Antônio Carlos Shimano; Alfredo Quites Antoniazzi; Melissa Orlandin Premaor; Fabio Vasconcellos Comim

doi:10.1016/j.bonr.2023.101710

Bone strength is reduced in a neonatal androgenized rat model

Bone Rep. 2023 Aug 19:19:101710. doi: 10.1016/j.bonr.2023.101710. eCollection 2023 Dec.

Authors

Affiliations

¹ Animal Science Department, Cooperative University of Colombia (UCC), Bucaramanga, Colombia.
² Laboratory of Biotechnology and Animal Reproduction - BioRep, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
³ Animal Care Facility, Federal University of Santa Maria (UFSM), Santa Maria, Brazil.
⁴ Department of Oral Pathology and Surgery, Faculty of Dentistry, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
⁵ Department of Metallurgical and Materials Engineering, Faculty of Engineering, Federal University of Minas Gerais, Belo Horizonte (UFMG), Minas Gerais, Brazil.
⁶ Department of Biomechanics, Medicine and Locomotor Apparatus Rehabilitation, Faculty of Medicine, University of Sao Paulo (USP), Ribeirão Preto, São Paulo, Brazil.
⁷ Department of Clinical Medicine, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, Brazil.

Abstract

Background: Whether polycystic ovary syndrome (PCOS) affects bone health during a woman's lifespan remains controversial. An androgenized rodent model replicated many metabolic and reproductive features of women with PCOS, and we aimed to use it to investigate the impact of androgens on microarchitecture (by micro-CT), bone mechanical strength, bone formation and resorption markers in rats with intact ovaries (SHAM) who underwent oophorectomy.

Methods: Wistar rats (Rattus norvegicus albinus) were employed for the experiments in this study. The protocol of androgenization consisted of the application of 1.25 mg s.c. testosterone propionate beteween days 2-5 of life, while the controls received the same amount of corn oil s.c. as previously established. Androgenized SHAM rats exhibited chronic anovulation identified by vaginal cytology and a reduction in the proportion of corpus luteum in the ovary in comparison to control SHAM rats. The realization of the ovariectomy or SHAM procedure occurred on Day 100 of life. All groups (n = 8) were followed-up for 180 days to address the study endpoints.

Results: Micro-CT from androgenized female rats (SHAM) showed a divergence between the trabecular and cortical bone profiles. Compared to SHAM controls, these rats had an increase in trabecular bone mass with a diminution in bone resorption C-terminal telopeptide of type 1 collagen (CTX) (p < 0.05), a concomitant decrease in cortical area and thickness in the femur, and a reduction in the strength of the femur on the mechanical test (p < 0.01).

Conclusions: Our results suggest that a reduction in the cortical thickness and cortical area observed in PCOS model rats was associated with a reduced strength of the femur, despite increased trabecular formation. Ovariectomy in the androgenized OVX group limited the progression rate of cortical bone loss, resulting in bone resistance and cortical thickness comparable to those observed in the control OVX group.

Keywords: Animal models of PCOS; Bone; Mechanical test; Polycystic ovary syndrome; microCT.

Associated data

figshare/10.6084/m9.figshare.17088803