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Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.

ABSTRACT: To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring.Animal (rat) study.Research laboratory.Female Sprague-Dawley rats.Food restriction during the second half of pregnancy in rats.Circulating gonadotropins, antimüllerian hormone (AMH), ovarian morphology, estrous cyclicity, and gene expression studies in the hypothalamus and ovary in 1-day-old (P1) and aging adult offspring.Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. In addition, 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age, with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity, with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating T, increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma LH/FSH levels, a reduction in E2 levels, and no changes in AMH in adult LBW offspring compared with in control offspring. Hypothalamic expression of leptin receptor (ObRb), estrogen receptor-? (ER-?), and GnRH protein was altered in an age-dependent manner with increased ObRb and ER-? expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami.Our data indicate that the maternal nutritional environment programs the reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to the development of obesity and hyperleptinemia in these animals in adult life.

SUBMITTER: Khorram O

PROVIDER: S-EPMC4282592 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.

Khorram Omid O Keen-Rinehart Erin E Chuang Tsai-Der TD Ross Michael G MG Desai Mina M

Fertility and sterility 20141028 1

<h4>Objective</h4>To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring.<h4>Design</h4>Animal (rat) study.<h4>Setting</h4>Research laboratory.<h4>Animal(s)</h4>Female Sprague-Dawley rats.<h4>Intervention(s)</h4>Food restriction during the second half of pregnancy in rats.<h4>Main outcome measure(s)</h4>Circulating gonadotropins, antimüllerian hormone (AMH), ovarian morphology, estrous cyclicity, and gene expression studies in the hypothalamus and o ...[more]

PMID: 25439841

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Project description:BackgroundWe have shown recently that maternal undernutrition (UN) advanced female pubertal onset in a manner that is dependent upon the timing of UN. The long-term consequence of this accelerated puberty on ovarian function is unknown. Recent findings suggest that oxidative stress may be one mechanism whereby early life events impact on later physiological functioning. Therefore, using an established rodent model of maternal UN at critical windows of development, we examined maternal UN-induced changes in offspring ovarian function and determined whether these changes were underpinned by ovarian oxidative stress.Methodology/principal findingsOur study is the first to show that maternal UN significantly reduced primordial and secondary follicle number in offspring in a manner that was dependent upon the timing of maternal UN. Specifically, a reduction in these early stage follicles was observed in offspring born to mothers undernourished throughout both pregnancy and lactation. Additionally, antral follicle number was reduced in offspring born to all mothers that were UN regardless of whether the period of UN was restricted to pregnancy or lactation or both. These reductions were associated with decreased mRNA levels of genes critical for follicle maturation and ovulation. Increased ovarian protein carbonyls were observed in offspring born to mothers UN during pregnancy and/or lactation and this was associated with peroxiredoxin 3 hyperoxidation and reduced mRNA levels; suggesting compromised antioxidant defence. This was not observed in offspring of mothers UN during lactation alone.ConclusionsWe propose that maternal UN, particularly at a time-point that includes pregnancy, results in reduced offspring ovarian follicle numbers and mRNA levels of regulatory genes and may be mediated by increased ovarian oxidative stress coupled with a decreased ability to repair the resultant oxidative damage. Together these data are suggestive of maternal UN potentially contributing to premature ovarian ageing in offspring.

Project description:IntroductionGestational chronodisruption impact maternal circadian rhythms, inhibiting the nocturnal increase of melatonin, a critical hormone that contributes to maternal changes adaptation, entrains circadian rhythms, and prepares the fetus for birth and successful health in adulthood. In rats, we know that gestational chronodisruption by maternal chronic photoperiod shifting (CPS) impaired maternal melatonin levels and resulted in long-term metabolic and cardiovascular effects in adult male offspring. Here, we investigated the consequences of CPS on mother and adult female offspring and explored the effects of melatonin maternal supplementation. Also, we tested whether maternal melatonin administration during gestational chronodisruption rescues maternal circadian rhythms, pregnancy outcomes, and transcriptional functions in adult female offspring.MethodsFemale rats raised and maintained in photoperiod 12:12 light: dark were mated and separated into three groups: (a) Control photoperiod 12:12 (LD); (b) CPS photoperiod; and (c) CPS+Mel mothers supplemented with melatonin in the drinking water throughout gestation. In the mother, we evaluated maternal circadian rhythms by telemetry and pregnancy outcomes, in the long-term, we study adult female offspring by evaluating endocrine and inflammatory markers and the mRNA expression of functional genes involved in adrenal, cardiac, and renal function.ResultsIn the mothers, CPS disrupted circadian rhythms of locomotor activity, body temperature, and heart rate and increased gestational length by almost 12-h and birth weight by 12%, all of which were rescued by maternal melatonin administration. In the female offspring, we found blunted day/night differences in circulating levels of melatonin and corticosterone, abnormal patterns of pro-inflammatory cytokines Interleukin-1a (IL1a), Interleukin-6 (IL6), and Interleukin-10 (IL10); and differential expression in 18 out of 24 adrenal, cardiac, and renal mRNAs evaluated.ConclusionMaternal melatonin contributed to maintaining the maternal circadian rhythms in mothers exposed to CPS, and the re-establishing the expression of 60% of the altered mRNAs to control levels in the female offspring. Although we did not analyze the effects on kidney, adrenal, and heart physiology, our results reinforce the idea that altered maternal circadian rhythms, resulting from exposure to light at night, should be a mechanism involved in the programming of Non-Communicable Diseases.

Project description:Key pointsPaternal obesity negatively influences metabolic outcomes in adult rat offspring. Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers. Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring. Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers. This paper presents a feasible, low-cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity.AbstractWe investigated whether maternal exercise before and during gestation could attenuate the negative metabolic effects of paternal high-fat diet-induced obesity in female adult rat offspring. Fathers consumed a normal chow or high-fat diet before mating. Mothers exercised on a treadmill before and during gestation or remained sedentary. In adulthood, female offspring were assessed using intraperitoneal insulin and glucose tolerance tests (IPITT and IPGTT, respectively), pancreatic morphology, ex vivo skeletal muscle insulin-stimulated glucose uptake and mitochondrial respiratory function. Paternal obesity impaired whole-body and skeletal muscle insulin sensitivity and insulin secretion in adult offspring. Maternal exercise attenuated the lower insulin-stimulated glucose uptake in offspring sired by obese fathers but distal insulin signalling components (p-AKT Thr308 and Ser473, p-TBC1D4 Thr642 and GLUT4) remained unchanged (P > 0.05). Maternal exercise increased citrate synthase activity only in offspring sired by obese fathers. Maternal exercise also reversed the lower insulin secretion in vivo observed in offspring of obese fathers, probably due to an attenuation of the decrease in pancreatic beta cell mass. In summary, maternal exercise before and during pregnancy in rats attenuated skeletal muscle insulin resistance and attenuated the decrease in pancreatic beta cell mass and insulin secretion observed in the female offspring of obese fathers.

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Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.

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Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.

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