Maternal Exposure to Phthalate and/or Diethylstilbestrol Leads to Long-Term Changes in Hypothalamic Gene Expression and Adult Behavior in Male and Female Offspring.

2011 ◽  
Vol 85 (Suppl_1) ◽  
pp. 790-790
Author(s):  
Richard Ivell ◽  
Damien Hunter ◽  
Kee Heng ◽  
Navdeep Mann ◽  
Ravinder Anand-Ivell
Keyword(s):  
Gene Expression ◽  
Female Offspring ◽  
Maternal Exposure ◽  
Male And Female ◽  
Adult Behavior ◽  
Long Term Changes

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

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.

scholarly journals Short- and long-term changes in gene expression mediated by the activation of TLR9

2010 ◽  
Vol 47 (6) ◽  
pp. 1317-1324 ◽  
Author(s):  
Sven Klaschik ◽  
Debra Tross ◽  
Hidekazu Shirota ◽  
Dennis M. Klinman
Keyword(s):  
Gene Expression ◽  
Long Term Changes ◽  
Short And Long Term

scholarly journals Adolescent Social Isolation Reprograms the Medial Amygdala: Transcriptome and Sex Differences in Reward

2020 ◽  
Author(s):  
Deena M. Walker ◽  
Xianxiao Zhou ◽  
Aarthi Ramakrishnan ◽  
Hannah M. Cates ◽  
Ashley M. Cunningham ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Isolation ◽  
Medial Amygdala ◽  
Isolation Stress ◽  
Transcriptional Profiles ◽  
Network Analyses ◽  
Long Term Changes ◽  
Differential Gene ◽  
Key Driver

ABSTRACTAdolescence is a sensitive window for reward- and stress-associated behavior. Although stress during this period causes long-term changes in behavior in males, how females respond is relatively unknown. Here we show that social isolation stress in adolescence, but not adulthood, induces persistent but opposite effects on anxiety- and cocaine-related behaviors in male vs. female mice, and that these effects are reflected in transcriptional profiles within the adult medial amygdala (meA). By integrating differential gene expression with co-expression network analyses, we identified crystallin mu (Crym), a thyroid-binding protein, as a key driver of these transcriptional profiles. Manipulation of Crym specifically within adult meA neurons recapitulates the behavioral and transcriptional effects of social isolation and re-opens a window of plasticity that is otherwise closed. Our results establish that meA is essential for sex-specific responses to stressful and rewarding stimuli through transcriptional programming that occurs during adolescence.

scholarly journals Long-term culture expanded alveolar macrophages restore full epigenetic identity in vivo

2021 ◽  
Author(s):  
Michael Sieweke ◽  
Sethuraman Subramanian ◽  
Clara Busch ◽  
Kaaweh Molawi ◽  
Laufey Geirsdottir ◽  
...  
Keyword(s):  
Gene Expression ◽  
Alveolar Macrophages ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Open Chromatin ◽  
Mechanistic Analysis ◽  
Long Term Changes ◽  
Cellular Identity

Abstract Alveolar macrophages (AM) are tissue resident macrophages of the lung that can be expanded in culture, but it is unknown to what extent culture affects their in vivo identity. Here we show that long-term ex vivo expanded mouse AM (exAM) maintain core AM gene expression but show culture adaptations related to adhesion, metabolism and proliferation. Strikingly, even after several months in culture exAM reacquired full transcriptional and epigenetic identity upon transplantation into the lung and could self-maintain in the natural niche long-term. Changes in open chromatin regions (OCR) observed in culture were fully reversible in transplanted exAM (texAM) and resulted in a gene expression profile indistinguishable from resident AM. Our results demonstrate that long-term proliferation of AM in culture does not compromise cellular identity in vivo. The demonstrated robustness of exAM identity provides new opportunities for mechanistic analysis and highlights the therapeutic potential of ex vivo expanded macrophages.

scholarly journals High Maternal Omega-3 Supplementation Dysregulates Body Weight and Leptin in Newborn Male and Female Rats: Implications for Hypothalamic Developmental Programming

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 89
Author(s):  
Soniya Xavier ◽  
Jasmine Gili ◽  
Peter McGowan ◽  
Simin Younesi ◽  
Paul F. A. Wright ◽  
...  
Keyword(s):  
Maternal Diet ◽  
Female Offspring ◽  
Female Rats ◽  
Omega 3 ◽  
Male And Female ◽  
Offspring Development ◽  
Metabolic Outcomes ◽  
Male And Female Rats ◽  
The Impact

Maternal diet is critical for offspring development and long-term health. Here we investigated the effects of a poor maternal diet pre-conception and during pregnancy on metabolic outcomes and the developing hypothalamus in male and female offspring at birth. We hypothesised that offspring born to dams fed a diet high in fat and sugar (HFSD) peri-pregnancy will have disrupted metabolic outcomes. We also determined if these HFSD-related effects could be reversed by a shift to a healthier diet post-conception, in particular to a diet high in omega-3 polyunsaturated fatty acids (ω3 PUFAs), since ω3 PUFAs are considered essential for normal neurodevelopment. Unexpectedly, our data show that there are minimal negative effects of maternal HFSD on newborn pups. On the other hand, consumption of an ω3-replete diet during pregnancy altered several developmental parameters. As such, pups born to high-ω3-fed dams weighed less for their length, had reduced circulating leptin, and also displayed sex-specific disruption in the expression of hypothalamic neuropeptides. Collectively, our study shows that maternal intake of a diet rich in ω3 PUFAs during pregnancy may be detrimental for some metabolic developmental outcomes in the offspring. These data indicate the importance of a balanced dietary intake in pregnancy and highlight the need for further research into the impact of maternal ω3 intake on offspring development and long-term health.

scholarly journals Exposure to Di(2-ethyl-hexyl) phthalate (DEHP) in Utero and during Lactation Causes Long-Term Pituitary-Gonadal Axis Disruption in Male and Female Mouse Offspring

Endocrinology ◽  
2012 ◽  
Vol 153 (2) ◽  
pp. 937-948 ◽  
Author(s):  
Paola Pocar ◽  
Nadia Fiandanese ◽  
Camillo Secchi ◽  
Anna Berrini ◽  
Bernd Fischer ◽  
...  
Keyword(s):  
Female Offspring ◽  
In Utero ◽  
Male And Female ◽  
Ethyl Hexyl ◽  
Lower Body Weight ◽  
Estrogen Synthesis ◽  
Pregnancy And Lactation ◽  
Weight Decrease ◽  
And Function

The present study examined the effects in mice of exposure to di(2-ethyl-hexyl) phthalate (DEHP) throughout pregnancy and lactation on the development and function of the pituitary-gonadal axis in male and female offspring once they have attained adulthood. Groups of two to three dams were exposed with the diet from gestational d 0.5 until the end of lactation, at 0, 0.05, 5, and 500 mg DEHP/kg · d. The experiment was repeated three times (total: seven to 10 dams per treatment). The 500-mg dose caused complete pregnancy failure, whereas exposure to doses of 0.05 and 5 mg did not affect pregnancy and litter size. In total, about 30 male and 30 female offspring per group were analyzed. Offspring of the DEHP-treated groups, compared with controls, at sexual maturity showed: 1) lower body weight (decrease 20–25%, P < 0.001); 2) altered gonad weight (testes were ∼13% lighter and ovaries ∼40% heavier; P < 0.001); 3) poor germ cell quality (semen was ∼50% less concentrated and 20% less viable, and ∼10% fewer oocytes reached MII stage, P < 0.001); 4) significant lower expression of steroidogenesis and gonadotropin-receptor genes in the gonads; and 5) up-regulated gonadotropin subunit gene expression in the pituitary. In conclusion, our findings suggest that, in maternally exposed male and female mice, DEHP acts on multiple pathways involved in maintaining steroid homeostasis. Specifically, in utero and lactational DEHP exposure may alter estrogen synthesis in both sexes. This, in turn, induces dysregulation of pituitary-gonadal feedback and alters the reproductive performance of exposed animals.

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