scholarly journals Hypercaloric diets impair ovarian follicular development by inducing hyperinsulinemia and hyperlipidemia in female mice

2020 ◽  
Author(s):  
Qiaoli Zhang ◽  
Yan Wang ◽  
Jiansheng Liu ◽  
Zi-Jiang Chen ◽  
Yanzhi Du

Abstract Long-term hypercaloric diets adversely impact ovarian follicular development and fecundity. We investigated the effects of high sugar (HS), high fat low sugar (HFLS), and high fat normal sugar (HFNS) diets on ovarian follicular development by feeding mice for up to 180 days. Body weight, gonadal fat, glucose, lipid, insulin, estrous cycle, sex hormones, ovarian tissues, and follicle ultrastructure were examined, and the expression of metabolism-related proteins was evaluated immunoblotting in ovarians. The mice on hypercaloric diets showed hyperinsulinemia and hyperlipidemia and exhibited heavier body and gonadal fat weights, longer estrous cycles, and fewer numbers of preantral and antral follicles; and the follicles that did form had impaired organelle morphology. The sex hormone levels in blood were similar to controls, excepting significantly elevated estradiol levels for the HS diet. In ovarian tissues, AMPKα phosphorylation was reduced while AKT phosphorylation and caspase-3 were increased in ovarian tissues in mice on all three hypercaloric diets. The data from our study collectively indicates possible mechanisms through which long-term exposure to unhealthy hypercaloric diets may impair ovarian follicular development: hyperinsulinemia and hyperlipidemia.

Animals ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 1111 ◽  
Author(s):  
Yuxin Zheng ◽  
Lizhu Ma ◽  
Ning Liu ◽  
Xiaorong Tang ◽  
Shun Guo ◽  
...  

Follicular atresia is closely related to both apoptosis and autophagy of granulosa cells (GCs) in ovarian follicles. In the present study, GCs were isolated from pig ovaries in small, medium and large antral follicles, and the current results showed that the proliferation of GCs was higher in medium follicles, and lower in large follicles compared to small follicles. The Bax and Caspase 3 mRNA levels were significantly higher, but the ratio of Bcl-2/Bax was lower in GCs of large follicles. The marker genes of autophagy, Atg3, Atg7 and LC3 mRNA levels were higher in GCs from medium follicles. Apoptosis- and autophagy-related proteins had a similar expression pattern to the mRNA level. Our results showed that phosphorylated ERK (p-ERK) was activated in GCs of large follicles, while phosphorylated AKT (p-AKT) and phosphorylated mTOR (p-mTOR) were inhibited in GCs of medium follicles. Labeling of autophagic vesicles with 4’,6-diamidino-2-phenylindole (DAPI) and monodansylcadaverine (MDC) confirmed the results of gene transcription and protein expression in GCs of different size follicles. We conclude that autophagy and apoptosis of GCs occurred in different size follicles during follicular development, and autophagy was mainly found in GCs of medium follicles, while apoptosis was mainly found in GCs of large follicles.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1145-1145
Author(s):  
Lirong Shen ◽  
Xin Liu ◽  
Yong Chen ◽  
Fangxiong Shi ◽  
Chao-Qiang Lai

Abstract Objectives Estrogen plays an important role in for growth and development of reproductive system in female. The major royal jelly (RJ) has a significant estrogenic-like effect for many female animals. The major RJ proteins (MRJPs) are the central constituents responsible for the physiological activities of RJ. In recent years, we have found that MRJPs possesses functions to increase fecundity associated with estrogenic effect in Drosophila. However, if MRJPs are the specific active ingredient mediating estrogenic effect of RJ and related action mechanism in mammalians remains unclear. Methods Neonatal immature female mice (FC) were divided into four groups fed MRJPs with doses of 0, 125, 250 and 500 mg/kg/body weight (M125, M250 and M500), respectively. The freeze-dried MRJPs powder was administrated daily for 45 consecutive days. The effects of MRJPs on the puberty onset, ovarian follicular development and serum estradiol levels in FC were evaluated. Results The times of estrus in M125, M250 and M500 were accelerated by 10.7%, 15.5% and 10.7%, the ovarian index of M125 and M250 and M500 were increased by 26.8% and 32.1% and 1.7%. The number of secondary follicles in M125 and M250 and M500 were increased by 50.7%,78.8% and 38.6%, the Graafian follicles in M125 and M250 and M500 were increased by 600.0% and 774.0% and 150.0%. M500 induced multi-oocyte follicles. The serum estradiol levels of M125, M250 and M500 were increased by 47.1%, 64.9% and 31.1%, the action of MRJPs raising hormone secretion level is mainly via upregulating expression of ERβ gene. Antioxidant parameters of ovarian tissue showed that the malondialdehyde levels in M125 and M250 were decreased, the superoxide dismutase activities and glutathione peroxidase activities in M125 and M250 were increased, respectively. Conclusions Oral administration of MRJPs may accelerate onset of puberty and promote follicular development in immature FM. The reproductive performance promotion of MRJPs was associated with raising estrogenic activity and antioxidant potential to reproductive system, upregulating expression of ERβ gene to raise hormone secretion and promote ovary development in FM. Funding Sources The National Natural Science Foundation of China and US Department of Agriculture, Agriculture Research Service.


2008 ◽  
Vol 70 (6) ◽  
pp. 946-955 ◽  
Author(s):  
J. Cavalieri ◽  
V.M. Smart ◽  
G. Hepworth ◽  
M. Ryan ◽  
K.L. Macmillan

2016 ◽  
Vol 7 (4) ◽  
pp. 384-390 ◽  
Author(s):  
L. Paixão ◽  
L. M. Velez ◽  
B. R. Santos ◽  
C. Tusset ◽  
S. B. Lecke ◽  
...  

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.


Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 416-424 ◽  
Author(s):  
Ningning Dang ◽  
Xianguang Meng ◽  
Shanshan Ma ◽  
Qian Zhang ◽  
XiYa Sun ◽  
...  

AbstractObjectiveTo investigate the effect of MDA-19 on progression of melanoma, and explore the relevant mechanism.MethodsThe melanoma cell lines, M14 and UACC257, were treated with different concentrations of MDA-19, then CCK8, clone formation assay, Transwell and flow cytometry assays were performed to examine cell proliferation, migration, invasion and apoptosis, respectively. The expression of apoptosis-related proteins (Bcl-2, Bax and caspase 3 P17), EMT and signaling pathway-related proteins were also detected by Western blot.ResultsMDA-19 inhibited melanoma cells in a dose-dependent manner. Compared to the NC group, MDA-19 significantly inhibited cell growth capacity, migration and invasion of M14 and UACC257 cells, and accelerated cell apoptosis in a mitochondrial pathway through regulating Bcl-2/Bax and Caspase 3 in M14 and UACC257 cells. Moreover, MDA-19 was observed to up-regulate the expression of E-cad and down-regulate the expression of N-cad, Vimentin and Slug in melanoma cells in vitro. Furthermore, MDA-19 could inhibit the PI3K/Akt pathway by blocking Akt phosphorylation (p-Akt) and downstream proteins, P70 and Cyclin D1 in M14 and UACC257 cells.ConclusionOur data demonstrate that MDA-19 could inhibit progression of melanoma by suppressing the PI3K/Akt pathway, suggesting that MDA-19 is a potential anti-cancer agent for therapy of melanoma.


2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 34-34
Author(s):  
Po-Ching P. Lin ◽  
CheMyong J. Ko

Reproduction ◽  
2006 ◽  
Vol 131 (4) ◽  
pp. 641-649 ◽  
Author(s):  
Inger B Carlsson ◽  
Mika P E Laitinen ◽  
Jennifer E Scott ◽  
Henna Louhio ◽  
Louiza Velentzis ◽  
...  

The receptor tyrosine c-Kit and its cognate ligand, c-Kit ligand (KL, stem cell factor, SCF), are involved in ovarian follicular development in several animal species. We studied the expression of KL and c-Kit usingin situhybridization and immunohistochemistry in donated human ovarian cortical tissue. The KL transcripts were expressed in granulosa cells of primary follicles, whereas the expression of c-Kit was confined to the oocyte and granulosa cells in primary and secondary follicles. We employed an ovarian organ culture using firstly serum-containing and then serum-free medium to study the effects of KL and an anti-c-Kit antibody, ACK2, on the development and survival of ovarian folliclesin vitro. Culture of ovarian cortical slices for 7 days resulted in a 37% increase in the number of primary follicles and a 6% increase in secondary follicles. The proportion of viable follicles decreased in all cultures. The addition of KL (1, 10 and 100 ng/ml) into the culture media did not affect the developmental stages of the follicles or the proportion of atretic follicles. Inclusion of ACK2 (800 ng/ml) in the culture medium significantly increased the proportion of atretic follicles on days 7 (49 vs 28% in control cultures) and 14 (62 vs 38%) of culture. In conclusion, c-Kit and KL are expressed in human ovaries during follicular development. Blocking the c-Kit receptor induces follicular atresia. The KL/c-Kit signaling system is likely to control the survival of human ovarian follicles during early follicular development.


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