GENDER-SPECIFIC INFLUENCE  OF Aу MUTATION ON PROGENY METABOLIC PHENOTYPE, FETAL GROWTH AND PLACENTAL GENE EXPRESSION IN MICE

Obesity during pregnancy increases the risk of obesity in offspring. To correct the offspring development in obese mothers, it is necessary to reveal the molecular mechanisms that mediate the influence of the maternal environment on the offspring ontogenesis. Leptin levels increase with obesity. In C57Bl mice, the Ау mutation is associated with elevated blood levels of leptin in pregnant females and exerts a gender-specific effect on the metabolic phenotype of mature offspring. Aim: to study the influence of Ау mutation on sensitivity to diet-induced obesity in male and female offspring, on fetal and placental weight and on the expression of genes in the placentas of the fetuses of different sexes. Body weight and food intake on a standard and an obesogenic diet, fetal and placental weights on pregnancy days 13 and 18, and gene expression of glucose transporters (GLUT1, GLUT3), neutral amino acid transporters (SNAT1, SNAT2, SNAT4), insulin-like growth factor 2 IGF2 and its receptor IGF2R were measured in male and female offspring of и ɑ/ɑ (control) and Ау/ɑ mothers. Ay mutation influenced the body weight only in male offspring, which consumed a standard diet, and did not influence obesity development in both male and female offspring. The weight of fetuses and placentas in Ау/ɑ as compared to ɑ/ɑ females was reduced on day 13 of pregnancy and was not different on day 18. On day 13 of pregnancy, the mRNA levels of the examined genes did not differ in placentas of male and female fetuses in ɑ/ɑ females. In Ау/ɑ females, the gene expression of GLUT1, GLUT3, SNAT1 and SNAT4 was reduced in female placentas compared to male placentas. The results suggest that the sex-specific transcription response of placentas to elevated leptin levels in pregnant Ау/ɑ females can mediate the gender-specific impact of Ау mutation on the offspring metabolism in postnatal life.

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Effect of neonatal hyperthyroidism on GH gene expression reprogramming and physiological repercussions in rat adulthood

Journal of Endocrinology ◽

10.1677/joe.1.06371 ◽

2006 ◽

Vol 190 (2) ◽

pp. 407-414 ◽

Cited By ~ 7

Author(s):

Kely de Picoli Souza ◽

Francemilson Goulart da Silva ◽

Maria Tereza Nunes

Keyword(s):

Gene Expression ◽

Body Weight ◽

Adult Life ◽

Control Group ◽

Postnatal Life ◽

Mrna Levels ◽

Mineral Density ◽

Thyroid State ◽

Gh Gene ◽

Neonatal Hyperthyroidism

The neonatal period (NP) is a critical phase of the development in which the expression pattern of most genes is established. Thyroid hormones (TH) play a key role in this process and, alterations in its availability in the NP may lead to different patterns of gene expression, which might reflect in the permanent expression of several genes in the adulthood. GH gene expression in the pituitary is greatly dependent on TH in the early postnatal life; thus, modifications of thyroid state in NP might lead to alterations in GH gene expression as well as to physiological repercussions in the adult life. This study aimed to investigate this possibility by means of the induction of a neonatal hyperthyroidism in rats (4 μg of 3,5,3′-triiodo-l-thyronine (T3)/100 g body weight, s.c.) for 5, 15 or 30 days, and further evaluation of GH gene expression, as well as its physiological consequences in adult rats subjected to a transient hyperthyroidism in the first 30 days of life. GH mRNA level was shown to be increased in T3-treated rats for 5 days; when the treatment was extended to 15 or 30 days, the GH mRNA levels were similar to the control group. Moreover, rats treated with T3 for 30 days and killed when 90 days old, i.e., 60 days at the end of the T3 treatment, showed decreased GH mRNA content, body weight, bone mineral density, and lean body mass. In conclusion: (1) T3 effects on GH gene expression depend on the period of life in which the hyperthyroidism is set and on the length of T3 treatment in the NP and (2) transient neonatal hyperthyroidism leads to a lower GH mRNA expression in adult life accompanied by physiological repercussions indicative of GH deficiency.

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Metformin-Mg2+ adjunct therapy synergistically modulates insulin and PDX-1 gene signatures in STZ-NAD induced diabetic model

Endocrinology&Metabolism International Journal ◽

10.15406/emij.2020.08.00281 ◽

2020 ◽

Vol 8 (3) ◽

pp. 66-71

Author(s):

Oluwaseun FAPOHUNDA ◽

Femi Abiola OGUNLEYE ◽

Tomisin Happy OGUNWA ◽

Idowu Olaposi OMOTUY ◽

Titilola Titilayoaderonke SAMUEL ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Treated Group ◽

Diabetic Rats ◽

The Body ◽

Distilled Water ◽

Mrna Levels ◽

Sprague Dawley ◽

Magnesium Supplementation ◽

Adjunct Therapy

Diabetes mellitus (DM) is a multi-factorial debilitating disorder of metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia) as a result of defects in either insulin secretion or insulin action in the body. DM is usually accompanied by hypomagnesemia. This study was aimed at investigating the effect of oral magnesium supplementation on pancreatic gene expression of insulin and PDX-1 in type-2 streptozotocin-nicotinamide induced Sprague dawley diabetic rats. A total of 24Sprague dawleyrats (Four groups of six rats each), were used for this study; Group 1: Normal rats (CONTROL) given distilled water for 4weeks; Group 2: Metformin + Magnesium treated rats (DMM) orally given 100mg/kg and 1000mg/kg body weight respectively for 4weeks; Group 3: Metformin treated diabetic rats (DM), orally given 100mg/kg body weight for 4weeks; Group 4: Diabetic untreated control rats (DU) given distilled water for 4weeks. Measured data were analyzed statistically. The result revealed that there was significant (p<0.05) increase in the feed and water intake of the treated rats but the metformin-magnesium supplement treated group showed more increase when compared with only metformin treated group. PDX-1 and insulin gene expression levels were significantly (p<0.05) higher in the control when compared with all the diabetic groups. However, PDX-1 and insulin mRNA levels were significantly (p<0.05) higher in DMM, when compared with DM. DMM showed improvements when compared with DM which suggests magnesium supplementation as an adjunct therapy with metformin may help inthe regeneration of the beta cells of the pancreas.

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Liver choline metabolism and gene expression in choline-deficient mice offspring differ with gender

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbaa047 ◽

2021 ◽

Vol 85 (2) ◽

pp. 447-451

Author(s):

Yukino Miyachi ◽

Kei Akiyama ◽

Yoshiko Tsukuda ◽

Thanutchaporn Kumrungsee ◽

Noriyuki Yanaka

Keyword(s):

Gene Expression ◽

Female Offspring ◽

Male Offspring ◽

Mrna Levels ◽

Choline Deficiency ◽

Deficient Diet ◽

Choline Metabolism ◽

Pregnancy And Lactation ◽

Gender Specific ◽

Deficient Mice

ABSTRACT Choline is an important nutrient during pregnancy and lactation. Maternal choline deficiency in CD-1 mice lowers liver betaine levels in male offspring. By contrast, it increases elovl3 and vanin-1 mRNA levels in female offspring. Taken together, these observations suggest gender-specific responses to a choline-deficient diet.

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Maternal obesity and fetal programming: effects of a high-carbohydrate nutritional modification in the immediate postnatal life of female rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.90460.2008 ◽

2008 ◽

Vol 295 (4) ◽

pp. E895-E903 ◽

Cited By ~ 25

Author(s):

Malathi Srinivasan ◽

Catherine Dodds ◽

Husam Ghanim ◽

Tao Gao ◽

Peter J. Ross ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Plasma Levels ◽

Body Weight Gain ◽

The Body ◽

Female Rats ◽

Milk Formula ◽

Postnatal Life ◽

Mrna Levels ◽

High Carbohydrate

Our earlier studies have shown that the artificial rearing of newborn rat pups [first generation high carbohydrate (1-HC)] on an HC milk formula resulted in chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Offspring [second-generation HC (2-HC)] of 1-HC female rats spontaneously acquired the HC phenotype in the postweaning period. In this study, we have characterized the development of the abnormal intrauterine environment in the 1-HC female rats and the effects on fetal development under such pregnancy conditions for the offspring. 1-HC female rats demonstrated hyperphagia on laboratory chow and increased body weight gain beginning from the immediate postweaning period along with hyperinsulinemia and hyperleptinemia. During pregnancy, 1-HC female rats showed several metabolic alterations including increased body weight gain and increased plasma levels of insulin, leptin, proinflammatory markers, and lipid peroxidation products. Although there were no significant changes in the body weights or litter size of term 2-HC fetuses, the plasma levels of insulin and leptin were significantly higher compared with those of control term fetuses. Quantitation of mRNA levels by real-time RT-PCR indicated significant increases in the mRNA levels of orexigenic neuropeptides in the hypothalamus of 2-HC term fetuses. Collectively, these results indicate that the HC diet in infancy results in an adverse pregnancy condition in female rats with deleterious consequences for the offspring.

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Maternal Exposure to Dibutyl Phthalate (DBP) or Diethylstilbestrol (DES) Leads to Long-Term Changes in Hypothalamic Gene Expression and Sexual Behavior

International Journal of Molecular Sciences ◽

10.3390/ijms22084163 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4163

Author(s):

Damien Hunter ◽

Kee Heng ◽

Navdeep Mann ◽

Ravinder Anand-Ivell ◽

Richard Ivell

Keyword(s):

Gene Expression ◽

Body Weight ◽

Sexual Behavior ◽

Reproductive Behavior ◽

Dibutyl Phthalate ◽

Female Offspring ◽

Male And Female ◽

Xenobiotic Exposure ◽

Long Term Changes

Xenobiotic exposure during pregnancy and lactation has been linked to perinatal changes in male reproductive outcomes and other endocrine parameters. This pilot study wished to assess whether brief maternal exposure of rats to xenobiotics dibutyl phthalate (DBP) or diethylstilbestrol (DES) might also cause long-term changes in hypothalamic gene expression or in reproductive behavior of the resulting offspring. Time-mated female Sprague Dawley rats were given either DBP (500 mg/kg body weight, every second day from GD14.5 to PND6), DES (125 µg/kg body weight at GD14.5 and GD16.5 only), or vehicle (n = 8–12 per group) and mild endocrine disruption was confirmed by monitoring postnatal anogenital distance. Hypothalamic RNA from male and female offspring at PND10, PND24 and PND90 was analyzed by qRT-PCR for expression of aromatase, oxytocin, vasopressin, ER-alpha, ER-beta, kisspeptin, and GnRH genes. Reproductive behavior was monitored in male and female offspring from PND60 to PND90. Particularly, DES treatment led to significant changes in hypothalamic gene expression, which for the oxytocin gene was still evident at PND90, as well as in sexual behavior. In conclusion, maternal xenobiotic exposure may not only alter endocrine systems in offspring but, by impacting on brain development at a critical time, can have long-term effects on male or female sexual behavior.

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PRE-MATERNAL ISOLATION EFFECTS ON BEHAVIOUR AND ENDOCRINE FUNCTION OF OFFSPRING

Acta Endocrinologica ◽

10.1530/acta.0.0620367 ◽

1969 ◽

Vol 62 (2) ◽

pp. 367-384 ◽

Cited By ~ 2

Author(s):

A. M. Sackler ◽

A. S. Weltman ◽

R. Schwartz ◽

P. Steinglass

Keyword(s):

Locomotor Activity ◽

Growth Rates ◽

Female Offspring ◽

The Body ◽

Endocrine Function ◽

Male And Female ◽

Isolation Stress ◽

Developmental Growth ◽

Body Weights ◽

And Control

ABSTRACT This report was designed to determine combined effects of maternal endocrine imbalances and abnormal behaviour due to prolonged isolation stress of female mice on the behaviour, developmental growth rate and endocrine function of their offspring. Sixty female albino mice averaging 19 g were divided equally into isolated and control groups. The isolated females were housed singly; control females were maintained in groups of 2 mice per cage. After observation of behavioural and physiological effects characteristic of isolation stress in the test mice, all isolated and control mice were mated after a 6½ month experimental, isolation period. No differences were observed in fertility and fecundity of the two groups of mothers. Analyses of developmental growth rates of the litters of the isolated versus control mothers showed significantly lower body weights in the test offspring at 3 and 4 weeks of age. The body weights of the female offspring remained significantly lower from the 4th to 11th weeks. The effects on the body weights of the male offspring declined and were no longer statistically significant at the 5th to 11 weeks. Locomotor activity at 4½ and 8 weeks of age was markedly or significantly higher in the male and female mice from isolated mothers. Tail-blood samples taken prior to autopsy at 5 and 11 weeks of age revealed significant decreases in the total leukocyte and eosinophil counts of both sexes. At the two ages, the absolute and relative spleen and thymus weights of the male and female offspring were markedly and/or significantly lower than the values observed in counterpart young from control females. Significant decreases were also observed in the absolute gonadal organ weights of both sexes at 11 weeks of age. The various data indicated inhibited growth rates, heightened locomotor activity and evasiveness, as well as evidence of increased adrenocortical function in the offspring from test mothers. The gonadal weight decreases suggested retarded gonadal development. Further studies using split-litter techniques are required to differentiate the effects of prenatal endocrine imbalances versus postnatal maternal influence (i. e., nursing care) on the offspring.

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Maternal low-protein diet programmes offspring growth in association with alterations in yolk leptin deposition and gene expression in yolk-sac membrane, hypothalamus and muscle of developing Langshan chicken embryos

British Journal Of Nutrition ◽

10.1017/s0007114509276434 ◽

2009 ◽

Vol 102 (6) ◽

pp. 848-857 ◽

Cited By ~ 25

Author(s):

Kaiqing Rao ◽

Jingjing Xie ◽

Xiaojing Yang ◽

Lei Chen ◽

Roland Grossmann ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Leptin Receptor ◽

Pectoralis Major Muscle ◽

Yolk Sac ◽

Pectoralis Major ◽

The Body ◽

Low Protein ◽

Igf I ◽

Offspring Growth

The present study was aimed to investigate the mechanism underlying the influence of maternal low-protein (LP) diet on offspring growth in the chicken. One hundred and twenty Chinese inbred Langshan breeder hens were allocated randomly into two groups fed diets containing low (10 %, LP) or normal (15 %) crude protein levels. Low dietary protein did not affect the body weight of hens, but significantly decreased the laying rate and egg weight. The yolk leptin content was significantly lower in eggs laid by LP hens, while no differences were detected for yolk contents of corticosterone, tri-iodothyronine (T3) or thyroxine. Despite significantly lower hatch weight, the LP offspring demonstrated obviously higher serum T3 concentration, which is in accordance with the faster post-hatch growth rate achieving significantly heavier body weight and pectoralis major muscle weight 4 weeks post-hatching. Expression of 20-hydroxysteroid dehydrogenase (20-HSD) mRNA in the yolk-sac membrane was significantly down-regulated at embryonic day 14, whereas that of transthyretin and leptin receptor (LepR) was not altered. Moreover, hypothalamic expression of 20-HSD, glucocorticoid receptors, thyrotropin-releasing hormone and LepR mRNA was significantly up-regulated in the LP group compared with their control counterparts. In the pectoralis major muscle, significantly higher expression of insulin-like growth factor (IGF)-I and IGF-I receptor mRNA was observed in LP embryos. The present study provides evidence that maternal LP diet programmes post-hatch growth of the offspring. The associated alterations in yolk leptin deposition as well as in yolk-sac membrane, fetal hypothalamus and muscle gene expression may be involved in mediating such programming effect in the chicken.

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Early Weaning Affects Liver Antioxidant Function in Piglets

Animals ◽

10.3390/ani11092679 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2679

Author(s):

Lihuai Yu ◽

Hongmin Li ◽

Zhong Peng ◽

Yuzhu Ge ◽

Jun Liu ◽

...

Keyword(s):

Gene Expression ◽

Body Weight ◽

Antioxidant Enzymes ◽

Liver Weight ◽

The Body ◽

Early Weaning ◽

Large White ◽

Enzymes Activity ◽

Antioxidant Function ◽

The Impact

This study examined the impact of early weaning on antioxidant function in piglets. A total of 40 Duroc × Landrace × Large White, 21-day-old piglets (half male and half female) were divided into suckling groups (SG) and weaning groups (WG). Piglets in WG were weaned at the 21st day, while the piglets in SG continued to get breastfed. Eight piglets from each group were randomly selected and slaughtered at 24th-day (SG3, WG3) and 28th-day old (SG7, WG7). The body weight, liver index, hepatocyte morphology, antioxidant enzymes activity, gene expression of antioxidant enzymes, and Nrf2 signaling in the liver of piglets were measured. The results showed that weaning caused decreased body weight (p < 0.01), lower liver weight (p < 0.01), and decreased the liver organ index (p < 0.05) of piglets. The area and size of hepatocytes in the WG group was smaller than that in the SG group (p < 0.05). We also observed that weaning reduced the activity of superoxide dismutase (SOD) and catalase (CAT) (p < 0.05) in the liver of piglets. Relative to the SG3 group, the gene expression of GSH-Px in liver of WG3 was significantly reduced (p < 0.05). The gene expression of Nrf2 in the SG3 group was higher than that in the WG3 group (p < 0.01). The gene expression of NQO1 in the SG7 group was higher than that in the WG7 group (p < 0.05). In conclusion, weaning resulted in lower weight, slowed liver development, and reduced antioxidant enzymes activity, thereby impairing liver antioxidant function and suppressing piglet growth.

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