Activation of PPARG inhibits dominant follicle development in cattle

Ferst, Juliana Germano; Rovani, Monique Tomazele; Dau, Andressa Minussi Pereira; Gasperin, Bernardo Garziera; Antoniazzi, Alfredo Q.; Bordignon, Vilceu; Oliveira, D.A; Gonçalves, Paulo Bayard Dias; Ferreira, Rogério

doi:10.1016/j.theriogenology.2019.10.032

Cited by 13 publications

(10 citation statements)

References 51 publications

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“…During all tested stages of the estrous cycle and pregnancy, Pparg activator reduces E2 secretion by the porcine corpora lutea explants (Kurzynska et al, 2014). In cattle, Pparg activation blocked follicle development (Ferst et al, 2020). In mammals, Pparg participate in follicular atresia by influencing boxidation of fatty acids, synthesis of cholesterol and sex steroid hormones (Cheng et al, 2021).…”

Section: Growth Performance and Ovarian Development In Spotted Scatmentioning

confidence: 99%

Ovary transcriptomic analysis reveals regulation effects of dietary fish oil on hormone, lipid, and glucose metabolism in female adult spotted scat (Scatophagus argus)

Wang

Liu

et al. 2022

Front. Mar. Sci.

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In the aquaculture industry, fish oil is widely used as a nutritional supplement to promote the gonadal maturation of broodstocks, while the mechanism of fish oil on ovary development remain unclear. Herein, female adult spotted scat (Scatophagus argus) with most ovaries at phase II were fed with diets containing 8% soybean oil (SO) or 8% fish oil (FO) for 60 days. The final average fish body weight was similar between FO and SO groups. The average gonadosomatic index (GSI) of FO group was higher (non-significant) than that of SO group. Finally, the phase IV ovary of the FO and SO groups were 7 and 5 out of 10, respectively. The serum estradiol (E2) level of the FO group was significantly higher than that of the SO group. The proportions of n-3 long-chain polyunsaturated fatty acids (LC-PUFA, such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA)) in the ovaries were much higher in the FO group than in the SO group. These results suggest that the maturity level of the FO group is relatively higher than that of the SO group. Transcriptome sequencing was used to detect the ovary gene expression. Comparatively, the ovary transcriptome analysis showed 68 up-regulated and 193 down-regulated genes in the FO group. The expression levels of Jund and Jun necessary for the ovary maturation were up-regulated in the FO group, while Pparγ and Cxcl12, which could inhibit the ovary development, were down-regulated in the FO group. Cyp3a27 coding the enzyme for degrading the estrogen was significantly down-regulated in the FO group and coincided with the increase of its serum E2. Kif5b which could regulate the glucose metabolism was up-regulated in the FO group. Serum insulin level was also increased in the FO group. Additionally, Aldh3a2 and Plin2 related to lipid metabolism were significantly down-regulated in the FO group. Briefly, dietary fish oil can influence the expression of genes related to steroid hormone, glucose and lipid metabolism. This study will clarify the mechanism of dietary fish oil in promoting ovary development in teleost fish.

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Section: Growth Performance and Ovarian Development In Spotted Scatmentioning

confidence: 99%

Ovary transcriptomic analysis reveals regulation effects of dietary fish oil on hormone, lipid, and glucose metabolism in female adult spotted scat (Scatophagus argus)

Wang

Liu

et al. 2022

Front. Mar. Sci.

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Section: Discussionmentioning

confidence: 99%

“…Although the exact functions of PPARs in the ovary are not fully understood, PPARγ has been shown to regulate granulosa cell proliferation, ovarian steroidogenesis, and tissue remodeling [143]. For instance, the overactivation of PPARγ through synthetic agonists (e.g., troglitazone) has been found to inhibit granulosa cell proliferation [67, 70], aromatase expression [117–119], and E2 secretion [67, 68, 70, 117–119, 144, 145]. In addition, the active metabolites of phthalates, such as mono-(2-ethylhexyl) phthalate (MEHP), have been found to activate PPARγ to inhibit aromatase expression and E2 secretion in both mouse primary granulosa cells [144, 146] and immortalized human KGN granulosa cells [147].…”

Section: Discussionmentioning

confidence: 99%

Ovarian disrupting effects and mechanisms of long- and short-chain per- and polyfluoroalkyl substances in mice

Pattarawat,

Zhan,

Fan

et al. 2024

Preprint

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BackgroundThe extensive use of per- and polyfluoroalkyl substances (PFAS) has led to environmental contamination and bioaccumulation. Previous research linked PFAS exposure to female reproductive disorders, but the mechanism remains elusive. Further, most studies focused on legacy long-chain PFOA and PFOS, yet the reproductive impacts of other long-chain PFAS and short-chain alternatives are rarely explored.ObjectivesWe investigated the effects and mechanisms of long- and short-chain PFAS on the ovary and associated ovarian functions.MethodsA 3Din vitroovarian follicle culture system and anin vivomouse model, together with approaches of reverse transcription-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, RNA-sequencing, pharmacological treatment,in situzymography, histology,in situhybridization, analytical chemistry, and benchmark dose modeling (BMD), were used to test environmentally relevant exposure levels of six long- and short-chain PFAS on follicle maturation, hormone secretion, and ovulation.ResultsIn vitroexposure revealed that long-but not short-chain PFAS interfered with gonadotropin-dependent follicle maturation, ovulation, and hormone secretion. Mechanistically, long-chain perfluorononanoic acid (PFNA) acted as a peroxisome proliferator-activated receptor gamma (PPARγ) agonist in granulosa cells to disrupt follicle-stimulating hormone (FSH)-dependent follicle maturation, luteinizing hormone (LH)-stimulated ovulation, and associated gene regulatory pathways.In vivomouse exposure confirmed the ovarian accumulation of PFNA and the mechanism of PPARγ-mediated ovarian toxicities of PFNA observedin vitro. The BMD analysis ofin vitroandin vivoresults suggested human relevant exposure levels of long-chain PFAS in our study pose an extra risk of ovarian defects, with follicular rupture as the most sensitive endpoint.DiscussionUsingin vitrofollicle culture andin vivomouse models, we discovered that long-chain PFAS interfere with gonadotropin-dependent follicle maturation, hormone secretion, and ovulation, posing a non-negligible risk to women’s reproductive health including anovulation, irregular menstrual cycles, and sub- or infertility.

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“…79,86 PPARG participates in lipid metabolism, estradiol and progesterone synthesis, and cell apoptosis. 87,88 Previous studies suggested that granulosa cells expressed AR, and could receive androgen and AR signaling regulation. 89 In the present study, the results of the co-culture experiments showed that compared to a single hyperandrogenic environment, the transcript levels of functional genes, IGF1, WT1, FOXO1, GATA6, and PPARG, were significantly decreased in granulosa cells in the presence of macrophages in a hyperandrogenic environment, the protein levels of CYP19a and FSHR were significantly reduced, granulosa cells were blocked in the G2-M phase and proliferation was inhibited, while the proinflammatory cytokine TNF-α was significantly elevated in the cell culture medium.…”

Section: Discussionmentioning

confidence: 99%

Hyperandrogenic environment regulates the function of ovarian granulosa cells by modulating macrophage polarization in PCOS

Chen,

Hong,

Diao

et al. 2024

American J Rep Immunol

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BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine‐metabolic disorder characterized by oligo‐anovulation, hyperandrogenism, and polycystic ovaries, with hyperandrogenism being the most prominent feature of PCOS patients. However, whether excessive androgens also exist in the ovarian microenvironment of patients with PCOS, and their modulatory role on ovarian immune homeostasis and ovarian function, is not clear.MethodsFollicular fluid samples from patients participating in their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment were collected. Androgen concentration of follicular fluid was assayed by chemiluminescence, and the macrophage M1:M2 ratio was detected by flow cytometry. In an in vitro model, we examined the regulatory effects of different concentrations of androgen on macrophage differentiation and glucose metabolism levels using qRT‐PCR, Simple Western and multi‐factor flow cytometry assay. In a co‐culture model, we assessed the effect of a hyperandrogenic environment in the presence or absence of macrophages on the function of granulosa cells using qRT‐PCR, Simple Western, EdU assay, cell cycle assay, and multi‐factor flow cytometry assay.ResultsThe results showed that a significantly higher androgen level and M1:M2 ratio in the follicular fluid of PCOS patients with hyperandrogenism. The hyperandrogenic environment promoted the expression of pro‐inflammatory and glycolysis‐related molecules and inhibited the expression of anti‐inflammatory and oxidative phosphorylation‐related molecules in macrophages. In the presence of macrophages, a hyperandrogenic environment significantly downregulated the function of granulosa cells.ConclusionThere is a hyperandrogenic microenvironment in the ovary of PCOS patients with hyperandrogenism. Hyperandrogenic microenvironment can promote the activation of ovarian macrophages to M1, which may be associated with the reprogramming of macrophage glucose metabolism. The increased secretion of pro‐inflammatory cytokines by macrophages in the hyperandrogenic microenvironment would impair the normal function of granulosa cells and interfere with normal ovarian follicle growth and development.

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Activation of PPARG inhibits dominant follicle development in cattle

Cited by 13 publications

References 51 publications

Ovary transcriptomic analysis reveals regulation effects of dietary fish oil on hormone, lipid, and glucose metabolism in female adult spotted scat (Scatophagus argus)

Ovary transcriptomic analysis reveals regulation effects of dietary fish oil on hormone, lipid, and glucose metabolism in female adult spotted scat (Scatophagus argus)

Ovarian disrupting effects and mechanisms of long- and short-chain per- and polyfluoroalkyl substances in mice

Hyperandrogenic environment regulates the function of ovarian granulosa cells by modulating macrophage polarization in PCOS

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