High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles
Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation....
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/21/3447 |
| _version_ | 1797468685290438656 |
|---|---|
| author | Chalikkaran Thilakan Rejani Ajit Kumar Navin Thekkey Madathil Valappil Mumthaz Venugopal Bhuvarahamurthy |
| author_facet | Chalikkaran Thilakan Rejani Ajit Kumar Navin Thekkey Madathil Valappil Mumthaz Venugopal Bhuvarahamurthy |
| author_sort | Chalikkaran Thilakan Rejani |
| collection | DOAJ |
| description | Pituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERβ, PR; and signaling proteins Wnt2 and β-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3β were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats. |
| first_indexed | 2024-03-09T19:11:03Z |
| format | Article |
| id | doaj.art-06e634a221c342b182e0118bbca382a1 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T19:11:03Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-06e634a221c342b182e0118bbca382a12023-11-24T04:08:54ZengMDPI AGCells2073-44092022-10-011121344710.3390/cells11213447High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian FolliclesChalikkaran Thilakan Rejani0Ajit Kumar Navin1Thekkey Madathil Valappil Mumthaz2Venugopal Bhuvarahamurthy3Department of Medical Biochemistry, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai 600113, Tamil Nadu, IndiaDepartment of Pharmaceutical Sciences, Texas A&M Health Science Centre, Texas A&M University, College Station, TX 77843, USADepartment of Zoology, Sir Syed College, Kannur 670142, Kerala, IndiaDepartment of Medical Biochemistry, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Chennai 600113, Tamil Nadu, IndiaPituitary gonadotropins directly govern ovarian functions, which are in turn regulated by the ovarian steroid hormones. The precise interplay of gonadotropins and steroid hormones is critical for follicle growth and differentiation. Furthermore, autophagy regulates ovarian follicle differentiation. However, how the high-fat-high fructose (HFD-HF) diet regulates gonadotropins and facilitates autophagy-mediated follicular differentiation in the ovary is obscure. We fed prepubertal rats (PND 25) an HFD-HF diet until PND 90. The results showed diminished adenohypophyseal GnRHR, PR, and aromatase expression, whereas AR, ERα, PRLR, and inhibin were augmented, resulting in gonadotropins decline. Interestingly, autophagy biomarkers, Beclin-1, ATG5, ATG12, LC3-II, and LAMP1 were reduced but SQSTM1/p62 was augmented in the ovaries of HFD-HF-fed rats, causing autolysosome to aggregation. The diet altered T, E2, P4, PRL, and their receptors status in the ovary, disturbed estrous cyclicity, and delayed vaginal opening. Ovarian histomorphology exhibited numerous cystic and atretic follicles, along with disturbed follicular maturation and ovulation. Moreover, the reduction of FSHR; steroidogenic proteins; receptor proteins AR, ERβ, PR; and signaling proteins Wnt2 and β-catenin was also noticed in the ovary, whereas PRLR, inhibin, and pGSK3β were augmented. In conclusion, exposure to a prepubertal HFD-HF diet leads to hypogonadotropism and the autophagy-mediated defective differentiation of ovarian follicles, abating fertility in adult rats.https://www.mdpi.com/2073-4409/11/21/3447autophagyGnRHRhypogonadotropism hypogonadismfolliculogenesissteroidogenesisinfertility |
| spellingShingle | Chalikkaran Thilakan Rejani Ajit Kumar Navin Thekkey Madathil Valappil Mumthaz Venugopal Bhuvarahamurthy High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles Cells autophagy GnRHR hypogonadotropism hypogonadism folliculogenesis steroidogenesis infertility |
| title | High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles |
| title_full | High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles |
| title_fullStr | High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles |
| title_full_unstemmed | High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles |
| title_short | High Fat-High Fructose Diet Elicits Hypogonadotropism Culminating in Autophagy-Mediated Defective Differentiation of Ovarian Follicles |
| title_sort | high fat high fructose diet elicits hypogonadotropism culminating in autophagy mediated defective differentiation of ovarian follicles |
| topic | autophagy GnRHR hypogonadotropism hypogonadism folliculogenesis steroidogenesis infertility |
| url | https://www.mdpi.com/2073-4409/11/21/3447 |
| work_keys_str_mv | AT chalikkaranthilakanrejani highfathighfructosedietelicitshypogonadotropismculminatinginautophagymediateddefectivedifferentiationofovarianfollicles AT ajitkumarnavin highfathighfructosedietelicitshypogonadotropismculminatinginautophagymediateddefectivedifferentiationofovarianfollicles AT thekkeymadathilvalappilmumthaz highfathighfructosedietelicitshypogonadotropismculminatinginautophagymediateddefectivedifferentiationofovarianfollicles AT venugopalbhuvarahamurthy highfathighfructosedietelicitshypogonadotropismculminatinginautophagymediateddefectivedifferentiationofovarianfollicles |