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Alteration in follistatin gene expression detected in prenatally androgenized rats
Marziyeh Salehi Jahromi1,2, Fahimeh Ramezani Tehrani2, Jennifer W Hill3
1a Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences , Tehran , Iran.
Abstract:
Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.
Insights
Prenatal androgen excess in rats disrupts ovarian follicle development, a key feature of polycystic ovarian syndrome (PCOS). This study found altered follistatin (FST) gene expression, not promoter methylation, in PCOS-like rats, impacting reproductive health.
Area of Science:
- Reproductive Endocrinology
- Developmental Biology
- Genetics
Background:
- Polycystic ovarian syndrome (PCOS) is characterized by impaired ovarian follicle development.
- Altered gene expression, including follistatin (FST), is implicated in PCOS pathogenesis.
- Prenatal exposure to excess androgens is a proposed risk factor for PCOS development.
Purpose of the Study:
- To investigate the impact of prenatal androgen excess on FST gene expression and promoter methylation in theca cells of adult female rats.
- To compare these molecular changes across different phases of the estrus cycle.
- To understand the role of FST in PCOS-like phenotypes induced by prenatal androgen exposure.
Main Methods:
- Wistar rats were exposed to testosterone or solvent in utero.
- Adult female offspring were categorized based on estrus cycle phases.
- Serum hormone levels, FST gene expression (RT-PCR), and promoter methylation (BSP) were analyzed.
Main Results:
- Prenatal androgen exposure resulted in a significant decrease in FST gene expression (0.85-fold) in the PCOS-like rat group compared to controls.
- While FST expression varied across estrus cycle phases, promoter methylation remained unchanged.
- Hormonal profiles and gonadotropin levels were also assessed.
Conclusions:
- Prenatal androgen excess leads to a PCOS-like phenotype in female rats.
- Irregular FST gene expression during the estrus cycle is associated with this phenotype.
- FST gene regulation, rather than promoter methylation, appears critical in PCOS development following prenatal androgen exposure.
