Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period
Abstract
1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Procurement and Maintenance of Experimental Animals
2.3. Experimental Design
2.4. Fertility Studies
2.5. Collection of Blood and Necropsy
2.6. Spermiogram Analysis
2.7. Testicular Cholesterol Levels (TCLs)
2.8. Analysis of Indicators of Oxidative Stress
2.9. Activity of Caspase-3
2.10. Testicular Steroidogenic Marker Enzymes Assay
2.11. Estimation of Proteins
2.12. Molecular Studies
2.13. RT-qPCR Studies to Validate Transcriptomic Data
2.14. Testicular Histology
2.15. Circulatory Levels of Reproductive Hormones
2.16. Testosterone
2.17. Serum FSH and LH
2.18. Statistical Analysis
3. Results
3.1. General Observations
3.2. Effect of Prepubertal Exposure to PFOA on Fertility in Adult Rats With or Without RES Supplementation
3.3. Effect of Prepubertal Exposure to PFOA on Body Weight and Tissue Somatic Indices in Adult Rats With or Without RES Supplementation
3.4. Effect of Prepubertal Exposure to PFOA on Qualitative and Quantitative Sperm Parameters, Testicular Steroidogenesis, and Serum Reproductive Hormones in Adult Rats With or Without RES Supplementation
3.5. Effect of Prepubertal Exposure to PFOA on the Histology of Testis in Adult Rats With or Without RES Supplementation
3.6. Effect of Prepubertal Exposure to PFOA on Pro- and Anti-Oxidant Status in the Testes and Epididymal Regions of Adult Rats With or Without RES Supplementation
3.7. Effect of Prepubertal Exposure to Perfluorooctanoic Acid (PFOA) on Activity Levels of Caspase-3 in Rat Testes at Their Adulthood
3.8. Gene Enrichment Analysis
3.9. Differential Gene Expression Analysis
3.10. Validation of RNA-Seq Data Using RT-qPCR
3.11. Gene Expression Studies
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Parameter | Control | PFOA Exposed | ||
---|---|---|---|---|
Untreated | RES | Untreated | RES | |
Number of litters | 10 | 10 | 10 | 10 |
No. of mating trails (days) | 1.48 a ± 0.27 | 1.52 a ± 0.31 (2.702) | 1.62 a ± 0.42 (9.459) | 1.49 a ± 0.39 (−1.97); (−8.02) |
Mating Index (%) | 100 | 100 | 100 | 100 |
Fertility Index (%) | 100 | 100 | 100 | 100 |
No. of corpora lutea/rat | 13.65 a ± 1.43 | 13.42 a ± 1.31 (−1.68) | 13.58 a ± 1.48 (−0.51) | 13.13 a ± 1.92 (−3.31); (−2.160) |
No. of implantations/rat | 12.78 a ± 1.02 | 12.89 a ± 1.21 (0.86) | 7.68 b ± 0.42 (−39.906) | 10.38 c ± 0.31 (−19.47); (35.156) |
Pre implantation loss (%) | 6.37 | 4.11 | 43.44 | 19.42 |
No. of live foetuses/rat | 12.02 a ± 0.39 | 11.91 b ± 0.28 (−0.92) | 5.07 c ± 0.18 (−57.820) | 10.21 d ± 0.28 (−14.27); (101.38) |
Post implantation loss (%) | 5.94 | 7.60 | 33.984 | 1.637 |
Body weight of pups (g) on PND 1 | 4.81 a ± 0.53 | 4.92 a ± 0.48 (2.286) | 4.84 a ± 0.51 (0.623) | 4.89 a ± 0.49 (−0.609); (1.03) |
Body weight of pups (g) on PND 21 | 30.28 a ± 1.71 | 29.48 a ± 1.68 (−2.642) | 30.09 a ± 1.59 (−0.627) | 30.07 a ± 1.74 (2.001); (−0.066) |
Parameters | Controls | PFOA Exposed | ||
---|---|---|---|---|
untreated | RES | Untreated | RES | |
Daily sperm count (millions/g epididymis) | 26.29 a ± 1.43 | 25.76 a ± 1.62 (−2.015) | 12.68 b ± 2.18 (−51.768) | 17.28 c ± 1.09 (−32.919); (36.277) |
Sperm analysis (epididymis) | ||||
Sperm count (millions/mL) | 74.68 a ± 4.32 | 73.91 a ± 5.21 (−1.031) | 40.31 b ± 4.38 (−46.023) | 59.73 c ± 3.22 (−19.185); (48.176) |
Sperm viability (%) | 73.9 a ± 3.2 | 72.98 a ± 4.33 (−1.244) | 39.28 b ± 4.09 (−46.847) | 60.12 c ± 4.82 (−17.621); (53.054) |
Sperm motility (%) | 70.18 a ± 4.29 | 69.33 a ± 3.47 (−1.211) | 37.28 b ± 3.19 (−46.879) | 59.22 c ± 3.43 (−14.582); (58.851) |
HOS tail coiled sperm (%) | 69.99 a ± 3.33 | 68.72 a ± 2.91 (−1.814) | 35.41 b ± 2.09 (−49.407) | 55.83 c ± 2.19 (−18.757); (57.667) |
Abnormalities of sperm (%) | 2.28 a ± 0.72 | 2.92 a ± 0.16 (28.070) | 22.94 b ± 2.39 (906.140) | 14.97 c ± 3.23 (412.67); (−34.742) |
Pin shaped (%) | 1 | 1 | 12 | 8 |
Rod shaped (%) | 1 | 1 | 10 | 6 |
Sperm transit time (days) | 6.91 a ± 1.02 | 7.01 a ± 1.22 (1.44) | 3.84 b ± 0.83 (−44.42) | 5.93 c ± 0.67 (−14.18); (35.24) |
Controls | PFOA Exposed | |||
---|---|---|---|---|
Parameters | Untreated | RES | Untreated | RES |
Total cholesterol (mg/g) | 6.01 a ± 0.41 | 5.92 a ± 0.31 (−1.497) | 10.08 b ± 0.16 (67.720) | 7.32 c ± 0.16 (23.648); (−27.3809) |
3β-HSD | 16.89 a ± 2.38 | 16.46 a ± 2.24 (−2.545) | 8.04 b ± 1.87 (−52.397) | 13.55 c ± 1.23 (−17.679); (68.532) |
17βHSD | 11.21 a ± 0.94 | 11.33 a ± 0.83 (1.070) | 5.01 b ± 0.32 (−55.307) | 8.05 c ± 0.66 (−28.949); (60.678) |
T (ng/mL) | 7.37 a ± 0.19 | 7.22 a ± 0.23 (−2.035) | 3.47 b ± 0.13 (−52.917) | 5.01 c ± 0.14 (−30.61); (44.380) |
FSH (ng/mL) | 8.27 a ± 0.91 | 8.17 a ± 0.31 (−1.209) | 15.97 b ± 0.81 (93.107) | 11.08 c ± 0.56 (35.62); (−30.62) |
LH (ng/mL) | 6.33 a ± 0.54 | 6.62 a ± 0.67 (4.581) | 16.44 b ± 1.71 (159.715) | 11.21 c ± 1.08 (69.34); (−31.813) |
Parameters | Control | PFOA exposed | |||
---|---|---|---|---|---|
Untreated | RES | Untreated | PFOA + RES | ||
LPx | Testis | 9.18 a ± 2.08 | 10.11 a ± 0.98 (10.130) | 27.14 b ± 2.39 (195.642) | 17.28 c ± 1.97 (70.92); (−36.33) |
Caput | 11.83 a ± 1.82 | 10.27 a ± 1.38 (−13.18) | 22.91 b ± 1.31 (93.660) | 14.38 c ± 0.97 (40.02); (−37.23) | |
corpus | 13.18 a ± 2.09 | 12.18 a ± 1.90 (−7.587) | 24.28 b ± 2.19 (84.218) | 16.18 c ± 0.93 (32.84); (−33.36) | |
Cauda | 10.21 a ± 1.03 | 11.27 a ± 2.03 (10.381) | 24.38 b ± 2.34 (138.785) | 15.28 c ±0.98 (35.58); (−37.33) | |
PC | Testis | 1.91 a ± 0.38 | 1.78 a ± 0.21 (−6.806) | 6.02 c ± 0.71 (215.18) | 3.62 d ± 0.29 (103.37); (−39.86) |
Caput | 1.38 a ± 0.623 | 1.53 a ± 0.531 (10.869) | 1.41 a ± 0.591 (2.173) | 1.43 a ± 0.487 (−6.54); (1.418) | |
corpus | 1.76 a ± 0.528 | 1.64 a ± 0.612 (−6.818) | 1.69 a ± 0.612 (−3.977) | 1.68 a ± 0.712 (2.43); (−0.59) | |
Cauda | 1.49 a ± 0.209 | 1.68 a ± 0.318 (12.751) | 3.12 b ± 0.291 (109.395) | 1.51 a ± 0.337 (−10.12); (−51.6) | |
H2 O2 | Testis | 10.38 a ± 0.42 | 9.27 b ± 0.32 (−10.693) | 22.19 c ± 1.38 (113.776) | 15.91 d ± 1.09 (71.63); (−28.30) |
Caput | 10.13 a ± 1.28 | 9.73 b ± 1.31 (−3.94) | 17.33 c ± 1.228 (71.076) | 13.48 d ± 0.97 (38.54); (−22.22) | |
corpus | 10.13 a ± 1.28 | 9.73 b ± 1.31 (−3.94) | 17.33 c ± 1.228 (71.076) | 13.48 d ± 0.97 (38.54); (−22.22) | |
Cauda | 10.92 a ± 1.08 | 11.32 a ± 1.09 (3.66) | 18.39 b ± 0.981 (68.406) | 14.08 c ± 1.07 (24.38); (−23.44) | |
O2− | Testis | 4.98 a ± 0.32 | 4.72 a ± 0.19 (−5.22) | 10.98 c ± 0.14 (120.481) | 7.27 d ± 0.18 (54.025); (−33.78) |
Caput | 5.17 a ± 0.431 | 4.89 a ± 0.581 (−5.415) | 7.82 b ± 0.281 (51.257) | 5.23 c ± 0.61 (6.95); (−33.12) | |
corpus | 4.27 a ± 0.312 | 4.31 a ± 0.302 (0.936) | 8.31 b ± 0.273 (94.613) | 5.18 c ± 0.428 (20.18); (−37.66) | |
Cauda | 4.39 a ± 0.414 | 4.41 a ± 0.281 (0.455) | 8.21 b ± 0.314 (87.015) | 5.21 c ± 0.513 (18.14); (−36.54) |
Parameters | Controls | Treated | |||
---|---|---|---|---|---|
Control | RES | PFOA | PFOA +RES | ||
SOD | Testis | 0.62 a ± 0.15 | 0.58 a ± 0.11 (−6.45) | 0.23 c ± 0.12 (−62.903) | 0.38 d ± 0.18 (−34.48); (65.217) |
Caput | 1.73 a ± 0.072 | 1.68 a ± 0.061 (−2.89) | 1.02 b ± 0.023 (−41.040) | 1.43 c ± 0.029 (−14.88); (40.196) | |
corpus | 1.54 a ± 0.033 | 1.52 a ± 0.042 (−1.29) | 1.08 c ± 0.019 (−29.870) | 1.39 d ± 0.013 (−8.552); (28.703) | |
Cauda | 1.68 a ± 0.041 | 1.71 a ± 0.038 (1.785) | 1.12 b ± 0.017 (−33.333) | 1.48 c ± 0.019 (−13.45); (32.142) | |
CAT | Testis | 0.48 a ± 0.013 | 0.51 a ± 0.041 (6.25) | 0.22 c ± 0.014 (−54.166) | 0.39 d ± 0.009 (−23.52); (77.27) |
Caput | 5.08 a ± 0.47 | 5.18 a ± 0.37 (1.968) | 3.07 b ± 0.21 (−39.566) | 4.97 a ± 0.38 (−4.05); (61.88) | |
corpus | 5.59 a ± 0.38 | 6.02 a ± 0.44 (7.692) | 3.12 b ± 0.29 (−44.186) | 4.82 c ± 0.37 (−19.93); (54.48) | |
Cauda | 5.73 a ± 0.39 | 6.12 a ± 0.51 (6.806) | 3.24 b ± 0.23 (−43.455) | 4.93 c ± 0.30 (−19.44); (52.160) | |
GR | Testis | 2.83 a ± 0.014 | 2.81 a ± 0.013 (−0.71) | 0.98 c ± 0.021 (−65.371) | 1.48 d ± 0.015 (−47.33); (51.020) |
Caput | 3.28 a ± 0.031 | 3.25 a ± 0.040 (−0.91) | 3.31 a ± 0.039 (0.914) | 3.27 a ± 0.049 (0.615); (−1.208) | |
corpus | 2.14 a ± 0.012 | 2.19 a ± 0.022 (2.23) | 4.29 c ± 0.027 (100.467) | 2.72 d ± 0.039 (24.200); (−36.596) | |
Cauda | 3.91 a ± 0.017 | 3.95 a ± 0.043 (1.02) | 2.44 c ± 0.031 (−37.595) | 3.73 d ± 0.024 (−5.569); (52.868) | |
GPx | Testis | 2.07 a ± 0.014 | 2.04 a ± 0.012 (−1.44) | 0.87 c ± 0.011 (−57.971) | 1.29 d ± 0.009 (−36.76); (48.27) |
Caput | 6.02 a ± 0.042 | 5.98 a ± 0.053 (−0.66) | 6.05 a ± 0.067 (0.49) | 5.95 a ± 0.081 (−0.501); (−1.65) | |
corpus | 5.11 a ± 0.039 | 5.13 a ± 0.023 (0.391) | 8.03 c ± 0.033 (57.142) | 5.13 a ± 0.063 (0); (−36.11) | |
Cauda | 4.74 a ± 0.051 | 4.79 a ± 0.024 (1.054) | 2.18 c ± 0.019 (−54.008) | 3.67 d ± 0.020 (−23.38); (68.34) | |
GSH | Testis | 10.48 a ± 1.21 | 11.29 a ± 2.08 (7.729) | 4.38 b ± 0.82 (−58.206) | 7.19 c ± 1.07 (−36.32); (64.15) |
Caput | 9.38 a ± 0.29 | 9.48 a ± 0.33 (1.066) | 10.02 b ± 0.42 (6.823) | 10.12 c ± 0.36 (6.75); (0.99) | |
corpus | 10.23 a ± 0.41 | 10.71 a ± 0.39 (4.692) | 11.18 b ± 0.46 (9.286) | 10.37 a ± 0.32 (−3.17); (−7.24) | |
Cauda | 9.32 a ± 0.23 | 9.30 a ± 0.29 (−0.22) | 5.27 c ± 0.17 (−43.454) | 7.98 d ± 0.20 (−14.19); (51.42) |
Controls | PFOA exposed | ||
---|---|---|---|
Untreated | RES | Untreated | RES |
190.42 a ± 20.74 | 192.78 a ± 30.44 (1.239) | 392.48 b ± 29.48 (106.112) | 272.28 c ± 22.53 (41.23); (−30.62) |
Term | Count | % | p-Value | Fold Enrichment |
---|---|---|---|---|
Testis | ||||
rno04215: Apoptosis—multiple species (up-regulated) | 6 | 14.28571 | 1.65 × 10−08 | 67.46324 |
rno00480: Glutathione metabolism (down-regulated)−pididymis | 4 | 8.695652 | 0.001779 | 15.92882 |
rno00480: Glutathione metabolism (up-regulated) | 3 | 1.923077 | 0.048064 | 6.371528 |
rno04976: Bile secretion (down-regulated) | 9 | 2.122642 | 9.61 × 10−04 | 4.392287 |
Fold Change * | Fold Change *# | |
---|---|---|
Gene Symbol | PFOA | PFOA + RES |
Testis | ||
hsd17β3 | −2.52 ± 0.04 | 1.23 ± 0.09 (−148.81) |
StAR | −1.84 ± 0.07 | 1.45 ± 0.11 (−178.80) |
AR | −2.04 ± 0.08 | 0.94 ± 0.14 (−146.07) |
Casp3 | 2.67 ± 0.09 | 1.02 ± 0.24 (−61.79) |
Nfe2l2 | −2.07 ± 0.03 | 1.55 ± 0.13 (−174.87) |
lhcgr | −2.79 ± 0.07 | 1.21 ± 0.11 (−143.36) |
Epididymis | ||
AR | −1.97 ± 0.05 | 0.96 ± 0.13 (−148.73) |
Alpha adrenoceptor 1 | −3.18 ± 0.06 | 0.87 ± 0.13 (−127.35) |
Muscarinic acetylcholine receptor 3 | −2.64 ± 0.11 | 1.11 ± 0.15 (−142.04) |
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Pavani, R.; Venkaiah, K.; Prakasam, P.G.; Dirisala, V.R.; Krishna, P.G.; Kishori, B.; Sainath, S.B. Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period. Toxics 2025, 13, 111. https://doi.org/10.3390/toxics13020111
Pavani R, Venkaiah K, Prakasam PG, Dirisala VR, Krishna PG, Kishori B, Sainath SB. Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period. Toxics. 2025; 13(2):111. https://doi.org/10.3390/toxics13020111
Chicago/Turabian StylePavani, R., K. Venkaiah, P. Gnana Prakasam, Vijaya R. Dirisala, P. Gopi Krishna, B. Kishori, and S. B. Sainath. 2025. "Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period" Toxics 13, no. 2: 111. https://doi.org/10.3390/toxics13020111
APA StylePavani, R., Venkaiah, K., Prakasam, P. G., Dirisala, V. R., Krishna, P. G., Kishori, B., & Sainath, S. B. (2025). Protective Effects of Resveratrol Against Perfluorooctanoic Acid-Induced Testicular and Epididymal Toxicity in Adult Rats Exposed During Their Prepubertal Period. Toxics, 13(2), 111. https://doi.org/10.3390/toxics13020111