scholarly journals Perinatal Dietary Protein Deficiency Alters Neurodevelopment and Reproductive Health of F0 and F1-Generations of Sprague-Dawley Rat Models

Author(s):  
Abey Nosarieme ◽  
Ebuehi Osaretin

Maternal and child health has been linked to the development of the human conceptus which absolutely depends on adequate and balanced supplies of key nutrients; therefore, an important element of reproductive health and neurodevelopment is improved nutritional status in women of child bearing age. Defect in neurodevelopment of newborn costs the mother both psychological and emotional stress, also reproductive health failure has been a significant public health concern, because it leads to disability in couples and individuals who bear the burden, there is therefore an urgent need to understand the underlying of birth malformation in order to channel possible solution. This study therefore sought to investigate the reproductive and neurodevelopmental defects in rat models of F 0 , F 1 and F 2 generations after modeled dietary protein deficiency, establishing the consequential mechanistic association. Rats in four groups were fed different ration of protein diet (PD); 21% PD, 10%PD, 5%PD and control diet (Normal rat chow), from adolescent through to gestation and Lactation, and next generations were weaned to the maternal diet group. Reproductive function and fertility index (including oestrus cyclicity, sexual response, histopathology and hormone profiling), as well as Neurobehavioral studies to include; Learning Memory tests (Y-maze, Moriz water maze, Elevated Plus Maze and Open field test) and Brain oxidative stress. Result shows significant reduction in the %fertility index and the overall reproductive function in the protein deficient models (5%PD; 35%2.5 10%PD; 66%2.2 as compared to 21%PD; 88.4%0.8, and control 85.8%1.3) which persist in subsequent generation. There was also observable transgenerational cognitive impairment reflected in: The Y-maze (Spatial memory: 5%; 8.3%, 10%; 9.25% 21%; 57.6% and control 55.95%), Morizz water Maze (5%: 26.5; 10%;21, 21%;5 and control; 6, as escape latency time), there was a significant decrease in the antioxidant capacity of the brain, especially in the 5%PD models. Brain serotonin and dopamine levels respectively; 5%: 2.70.3; 36.25 0.57., 10%; 2.90.3; 17.75 0.94., 21%;7.80.9; 7.951.1., and control; 70.2; 11.550.7. were significantly perturbed in the test model brains. Therefore, Protein deficiency is capable of causing a dysfunction in the reproductive health of models, by altering the oestrus cyclicity which is partly dependent on the changes in hormonal events, the brain redox status and neurotransmitter system. Therefore, persistent perinatal exposure to protein malnutrition increases the risk of cognitive defect and other brain disorders in subsequent generations. There was an evidence of metabolic reset in the malnourished group; this may be due in part to epigenetic regulation of transposable element.

Author(s):  
Abey Nosarieme

The maintenance of fertility status critically depends on the proper functioning of the ovary, which is also a reflect of normal development of ovarian follicles. Malnourished males and females have been scientifically proven to form a major infertile population in developing countries. Proper nutrition therefore forms a baseline for functional reproductive makeup. This study seeks to assess the mRNA expression level of ovarian inhibin alpha (IHA), Estrogen receptor (ERα), Aromatase, CCAAT-enhancer binding protein alpha (CEBPA) and Fibroblast Growth Factor Receptor 1 (FGFR1) in the F 0 and F 1 rat progeny subjected to perinatal dietary protein deficiency. Rats in four (4) groups were fed different grade of protein deficient diets (5%, 10%, 21% protein diets and rat chow). Total RNA was extracted from the snap frozen ovary excised from the different rat groups, checked for quality, converted the cDNA and RT-qPCR was used to quantify amount of each mRNA expressed in the tissue. Result shows severe alteration in the level of expression of some of the key genes assessed essential for sustenance of reproductive health from one generation to another. Inhibin alpha was downregulated while CEBPA was upregulated in 5%PD groups at F 1 and F 2, ERα was downregulated only at first generation but normalized in the second generation. Aromatase in the 10% group was upregulated at F 1 and F 2 generation, while in the 5%PD, it was downregulated only at F 2. These modulations mediate the effects of dietary protein deficiency on the ovarian and reproductive function from one generation to another.


2021 ◽  
Author(s):  
Nosarieme Omoregie Abey ◽  
Osaretin Albert Taiwo Ebuehi ◽  
Ngozi Awa Imaga

Abstract Background: The ability to reproduce efficiently is an important characteristic that has evolved through natural selection. Nutrition can modulate reproductive activities at different levels, its effect on nutrition is therefore complex and less predictable. This study aims at investigating the underlying effect of persistent dietary protein deficiency during early life on reproductive parameters of subsequent (F1 and F2) generations.Method: Rats in group of four (4) were fed daily, with different ration of protein diet (PD) formulated as: 21% protein diet, 10%protein diet, 5%protein diet and control diet (rat chow, containing 16-18% protein). They were fed ad libitum before mating, throughout gestation and lactation, and next generations were weaned to the maternal diet. Reproductive function analysis (which include; gestation and pubertal hormonal profiling, onset of puberty, oestrus cyclicity, sexual response) and morphometric analysis of the ovarian structure were carried out to assess associated consequences.Results: showed significant reduction in the fertility index as a consequence of altered reproductive function in the protein deficient models at P≤ 0.05. Low protein diet posed suboptimal intrauterine condition, which was linked to increased prenatal morbidity and mortality, lowered birthweight delayed onset of puberty, induced cycle irregularity, altered follicular maturation and endocrine dysfunction in the protein deficient groups. Reproductive status of an individual female organism critically depends on the maintenance of ovarian structure and function that has been associated with the hypothalamic pituitary-gonadal axis, hormonal events and sexual maturity.Conclusion: There is therefore an association between persistent early life protein deficiency and reproductive response which mechanistically involves life-long changes in key ovarian cytoarchitecture and function.


2016 ◽  
pp. 98-101
Author(s):  
Vl.V. Podolsky ◽  
◽  
V.V. Podolsky ◽  

The objective: the developing of a system of preventive measures and principles of pregravid preparation for women with somatoform disorders and violation of autonomic homeostasis (VAH), in which observed changes in reproductive health (CRH) in the shape of states after undergoing artificial abortion, infertility and uterine fibroids. Patients and methods. Conducted clinical and epidemiological studies in the population of women of fertile age (WFA) allowed identifying for further examination of women with CRH in the form of state after undergoing artificial abortion, infertility and uterine fibroids in women with VAH. Further women were examined, in particular the conducted clinical and instrumental methods of research; determined the state of autonomic homeostasis and psycho emotional health of the biotopes of the organism, immunity; analyzed the hormonal regulation of the menstrual cycle; performed genetic studies and determined the morphofunctional state of reproductive system. Results. The most frequent complications during pregnancy in women who had CRH in history in the form of abortions, infertility and uterine fibroids and in the background of the PAF, there was a threat of interruption of pregnancy (often in I and II trimester – 56%) and preterm delivery (21%). The study of the catamnesis of further reproductive health found that in the case of well-conducted therapeutic measures in women undergoing artificial abortion, had infertility and uterine leiomyoma in the background of VAH, restore reproductive function, and in 82% of cases occurred a pregnancy. Conclusion. The the provided study of reproductive health, and state of various organs and systems of fertile aged women with somatoform disorders and violations of the autonomic homeostasis allowed to develop preventive measures for these women and pregravid preparation with the inclusion to the therapy Magnesium and vitamins (Magne-В6®). Key words: somatoform disorders, violation of autonomic homeostasis, changes in reproductive health, prevention and treatment, women of fertile age, Magne-В6®.


Author(s):  
Burbaeva G.Sh. ◽  
Androsova L.V. ◽  
Vorobyeva E.A. ◽  
Savushkina O.K.

The aim of the study was to evaluate the rate of polymerization of tubulin into microtubules and determine the level of colchicine binding (colchicine-binding activity of tubulin) in the prefrontal cortex in schizophrenia, vascular dementia (VD) and control. Colchicine-binding activity of tubulin was determined by Sherlinе in tubulin-enriched extracts of proteins from the samples. Measurement of light scattering during the polymerization of the tubulin was carried out using the nephelometric method at a wavelength of 450-550 nm. There was a significant decrease in colchicine-binding activity and the rate of tubulin polymerization in the prefrontal cortex in both diseases, and in VD to a greater extent than in schizophrenia. The obtained results suggest that not only in Alzheimer's disease, but also in other mental diseases such as schizophrenia and VD, there is a decrease in the level of tubulin in the prefrontal cortex of the brain, although to a lesser extent than in Alzheimer's disease, and consequently the amount of microtubules.


Author(s):  
M. A. Fesenko ◽  
G. V. Golovaneva ◽  
A. V. Miskevich

The new model «Prognosis of men’ reproductive function disorders» was developed. The machine learning algorithms (artificial intelligence) was used for this purpose, the model has high prognosis accuracy. The aim of the model applying is prioritize diagnostic and preventive measures to minimize reproductive system diseases complications and preserve workers’ health and efficiency.


2020 ◽  
Vol 16 ◽  
Author(s):  
Dang Kim Thu ◽  
Dao Thi Vui ◽  
Nguyen Thi Ngoc Huyen ◽  
Nguyen Thi Thanh Binh ◽  
Nguyen Thi Huyen ◽  
...  

Background: Huperzia phlegmaria has been used for the treatment of neurological disorder. Alkaloids are main bioactive compounds found in Huperzia phlegmaria. We aimed to investigate the acetylcholinesterase (AChE) inhibitory activity in vitro of Huperzia phlegmaria alkaloid extract (HpAE) and protective effects on mice which were induced cognitive deficits by scopolamine. Methods: AChE inhibitory activity and kinetic inhibition mechanism was investigated by Ellman's assay. Mice were administrated orally HpAE (30 mg/kg and 60 mg/kg) for fourteen days, and injected scopolamine at a dose of 1 mg/kg intraperitoneally for four days to induce cognitive impairment. The Y-maze and the Morris water maze were used for evaluating the memory behaviors. Acetylcholine (ACh) levels and AChE activity were measured in brain tissue. Glutathione peroxidase (GPx), superoxide dismutase (SOD) activities, and malondialdehyde (MDA) groups were also evaluated in the mouse brain tissues. Results: Our data showed that HpAE had the strong AChE inhibitory activity with an IC50 value of 5.12 ± 0.48 μg/mL in a concentration-dependent manner. Kinetic inhibition analysis demonstrated that HpPAE inhibited AChE followed the mixed inhibition type with Ki (representing the affinity of the enzyme and inhibitor) was 4.37 ± 0.35 µg/mL. Scopolamine induced the cognitive impairment in Morris Water Maze and Y-maze test along with reduced brain levels of ACh and antioxidant enzyme and increased AChE activity in mouse brain tissues. Treatment with HpAE at both dose (30 mg/kg and 60 mg/kg) decreased the SCP-induced cognitive impairment in both behavioral tests along with decreased acetylcholinesterase activity and MDA level, and increased ACh level and antioxidant enzyme in mouse brain tissues. Conclusion: Our results suggested that the HpAE at both dose (30 mg/kg and 60 mg/kg) may be used for prevent and treatment of Alzheimer’s disease.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 134
Author(s):  
Stephanie Dooves ◽  
Arianne J. H. van Velthoven ◽  
Linda G. Suciati ◽  
Vivi M. Heine

Tuberous sclerosis complex (TSC) is a genetic disease affecting the brain. Neurological symptoms like epilepsy and neurodevelopmental issues cause a significant burden on patients. Both neurons and glial cells are affected by TSC mutations. Previous studies have shown changes in the excitation/inhibition balance (E/I balance) in TSC. Astrocytes are known to be important for neuronal development, and astrocytic dysfunction can cause changes in the E/I balance. We hypothesized that astrocytes affect the synaptic balance in TSC. TSC patient-derived stem cells were differentiated into astrocytes, which showed increased proliferation compared to control astrocytes. RNA sequencing revealed changes in gene expression, which were related to epidermal growth factor (EGF) signaling and enriched for genes that coded for secreted or transmembrane proteins. Control neurons were cultured in astrocyte-conditioned medium (ACM) of TSC and control astrocytes. After culture in TSC ACM, neurons showed an altered synaptic balance, with an increase in the percentage of VGAT+ synapses. These findings were confirmed in organoids, presenting a spontaneous 3D organization of neurons and glial cells. To conclude, this study shows that TSC astrocytes are affected and secrete factors that alter the synaptic balance. As an altered E/I balance may underlie many of the neurological TSC symptoms, astrocytes may provide new therapeutic targets.


Reproduction ◽  
2018 ◽  
Author(s):  
Susana B Rulli ◽  
María Julia Cambiasso ◽  
Laura D Ratner

In mammals, the reproductive function is controlled by the hypothalamic-pituitary-gonadal axis. During development, mechanisms mediated by gonadal steroids exert an imprinting at the hypothalamic-pituitary level, by establishing sexual differences in the circuits that control male and female reproduction. In rodents, the testicular production of androgens increases drastically during the fetal/neonatal stage. This process is essential for the masculinization of the reproductive tract, genitals and brain. The conversion of androgens to estrogens in the brain is crucial for the male sexual differentiation and behavior. Conversely, feminization of the brain occurs in the absence of high levels of gonadal steroids during the perinatal period in females. Potential genetic contribution to the differentiation of brain cells through direct effects of genes located on sex chromosomes is also relevant. In this review, we will focus on the phenotypic alterations that occur on the hypothalamic-pituitary-gonadal axis of transgenic mice with persistently elevated expression of the human chorionic gonadotropin hormone (hCG). Excess of endogenously synthesized gonadal steroids due to a constant hCG stimulation is able to disrupt the developmental programming of the hypothalamic-pituitary axis in both transgenic males and females. Locally produced estrogens by the hypothalamic aromatase might play a key role in the phenotype of these mice. The “four core genotypes” mouse model demonstrated a potential influence of sex chromosome genes in brain masculinization before critical periods of sex differentiation. Thus, hormonal and genetic factors interact to regulate the local production of the neurosteroids necessary for the programming of the male and female reproductive function.


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