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Obesity Triggers Dysregulation of Essential ABC Transporters in Rat Testis and Sperm
Péter Szatmári1, Kata Kira Kemény1, Adrienn Seres-Bokor1
1Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös Street 6, 6720 Szeged, Hungary.
Abstract:
Objectives: Obesity and the associated metabolic dysfunction influence fertility performance at molecular levels and ABC transporters are considered as potential molecular factors affecting fertility both in the testis and sperm; therefore, we aimed to examine the effect of a short-term diet-induced obesity on testicular and spermatic ABC transporters in a rat model focusing on the expressions of P-glycoprotein (P-gp, Abcb1) and breast cancer resistance protein (BCRP, Abcg2). The testicular androgen state involving aromatase enzyme (Cyp19a1), androgen receptor (Ar), and testosterone levels were also evaluated. Methods: Obesity was induced in male Sprague Dawley rats by feeding a high-fat, high-sugar diet (HFHSD) for 10 weeks, and metabolic status was evaluated using a glucose tolerance test. The weight and size of reproductive organs were measured, and Abcb1a/1b, Abcg2, Cyp19a1, and Ar expression in testes or sperm was determined by RT-PCR and Western blotting. At the same time, testosterone levels were measured by ELISA. Results: HFHSD successfully induced higher weight gain with glucose intolerance and reduced reproductive organ size. In obese rats, testicular Abcb1a and Abcb1b mRNA and P-gp protein expression were significantly higher, whereas testicular Abcg2 mRNA levels decreased. Spermatic Abcb1a, Abcb1b and Abcg2 mRNA expression also reduced in obesity. Neither testicular testosterone concentration nor Cyp19a1 and Ar mRNA expression levels changed after the 10-week obesogenic diet compared with controls. Conclusions: Overall, our study revealed infertility-related ABC transporter changes in obese male rats, suggesting that these alterations may predispose obese males to fertility impairments, even before the obesity-induced androgen dysregulation.
Insights
Diet-induced obesity alters ABC transporters in male rats, impacting fertility. These changes in P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) occur even without affecting testosterone levels.
Area of Science:
- Reproductive Biology
- Metabolic Dysfunction
- Molecular Biology
Background:
- Obesity and metabolic dysfunction negatively impact male fertility at a molecular level.
- ABC transporters, including P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), are implicated in testicular and sperm function.
- Diet-induced obesity models are crucial for understanding metabolic impacts on reproductive health.
Purpose of the Study:
- To investigate the effects of short-term diet-induced obesity on testicular and spermatic ABC transporter expression (P-gp/Abcb1 and BCRP/Abcg2) in a rat model.
- To evaluate the impact of obesity on the testicular androgen state, including aromatase (Cyp19a1), androgen receptor (Ar), and testosterone levels.
Main Methods:
- Male Sprague Dawley rats were fed a high-fat, high-sugar diet (HFHSD) for 10 weeks to induce obesity.
- Metabolic status was assessed via glucose tolerance tests; reproductive organ weights were measured.
- Gene and protein expression of Abcb1a/1b, Abcg2, Cyp19a1, and Ar in testes and sperm were analyzed using RT-PCR and Western blotting; testosterone levels were measured by ELISA.
Main Results:
- Obesity induction led to increased weight gain, glucose intolerance, and reduced reproductive organ size.
- Testicular P-gp (Abcb1a/1b) expression increased, while BCRP (Abcg2) expression decreased in obese rats.
- Spermatic expression of Abcb1a/1b and Abcg2 mRNA was reduced in obese rats; no significant changes were observed in testicular testosterone, Cyp19a1, or Ar mRNA levels.
Conclusions:
- Diet-induced obesity causes significant alterations in key ABC transporters within the testes and sperm of male rats.
- These ABC transporter changes may contribute to fertility impairments in obese males, independent of androgen dysregulation.
- The findings highlight ABC transporters as potential early molecular indicators of obesity-related male infertility.
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