Developmental programming: Adverse sexually dimorphic transcriptional programming of gestational testosterone excess in cardiac left ventricle of fetal sheep

Adverse in-utero insults during fetal life alters offspring\u27s developmental trajectory, including that of the cardiovascular system. Gestational hyperandrogenism is once such adverse in-utero insult. Gestational testosterone (T)-treatment, an environment of gestational hyperandrogenism, manifests as hypertension and pathological left ventricular (LV) remodeling in adult ovine offspring. Furthermore, sexual dimorphism is noted in cardiomyocyte number and morphology in fetal life and at birth. This study investigated transcriptional changes and potential biomarkers of prenatal T excess-induced adverse cardiac programming. Genome-wide coding and non-coding (nc) RNA expression were compared between prenatal T-treated (T propionate 100 mg intramuscular twice weekly from days 30 to 90 of gestation; Term: 147 days) and control ovine LV at day 90 fetus in both sexes. Prenatal T induced differential expression of mRNAs in the LV of female (2 down, 5 up) and male (3 down, 1 up) (FDR \u3c 0.05, absolute log2 fold change \u3e 0.5); pathways analysis demonstrated 205 pathways unique to the female, 382 unique to the male and 23 common pathways. In the male, analysis of ncRNA showed differential regulation of 15 lncRNAs (14 down, 1 up) and 27 snoRNAs (26 down and 1 up). These findings suggest sexual dimorphic modulation of cardiac coding and ncRNA with gestational T excess

Sex-Specific Impacts of Exercise on Cardiovascular Remodeling

Cardiovascular diseases (CVD) remain the leading cause of death in men and women. Biological sex plays a major role in cardiovascular physiology and pathological cardiovascular remodeling. Traditionally, pathological remodeling of cardiovascular system refers to the molecular, cellular, and morphological changes that result from insults, such as myocardial infarction or hypertension. Regular exercise training is known to induce physiological cardiovascular remodeling and beneficial functional adaptation of the cardiovascular apparatus. However, impact of exercise-induced cardiovascular remodeling and functional adaptation varies between males and females. This review aims to compare and contrast sex-specific manifestations of exercise-induced cardiovascular remodeling and functional adaptation. Specifically, we review (1) sex disparities in cardiovascular function, (2) influence of biological sex on exercise-induced cardiovascular remodeling and functional adaptation, and (3) sex-specific impacts of various types, intensities, and durations of exercise training on cardiovascular apparatus. The review highlights both animal and human studies in order to give an all-encompassing view of the exercise-induced sex differences in cardiovascular system and addresses the gaps in knowledge in the field

Liraglutide Improves Hypertension and Metabolic Perturbation in a Rat Model of Polycystic Ovarian Syndrome - Fig 1

<p><b>DHT levels and estrous cycle pattern:</b> a) <b>DHT levels measured at 16 weeks of age.</b> (Mean± SEM; pg/ml)<b>:</b> measured in the serum by ELISA, control group (n = 9) DHT group (n = 10) and DHT+ liraglutide group (n = 11). DHT levels were 1.3 fold higher in the DHT treated rats compared to control irrespective of liraglutide treatment (p<0.05). b) <b>Estrous cycle pattern in the three groups.</b> Vaginal cytology was done every day starting at 8 week of life till the end of the study. Data presented are from the last week of the study. The figure shows pattern of two representative rats in each group including control, DHT and DHT+ Liraglutide. P: proestrus; E: estrus; M: metestrus; and D: diestrus.</p

Effect of liraglutide on DHT induced weight gain.

<p>(Mean± SEM; g): a) Rats were weighed at 4 weeks and again from 9–13 weeks and at 16 week. “#” denotes p<0.05 between DHT and DHT+liraglutide and “@” denotes p <0.05 between DHT and control. b) Rate of weight change per week between 12–16 weeks. n = 12 rats in DHT and DHT+ liraglutide group n = 9 control group. * denotes p<0.05 between DHT +liraglutide and DHT and control.</p

Effect of liraglutide on DHT induced metabolic perturbation.

<p>(Mean± SEM): a) oral glucose tolerance test done at 16 weeks (n = 9 control, n = 8 DHT+liraglutide and n = 10 DHT). b): Area under the curve during OGTT for different groups. c): Total cholesterol measured at the end of the study (88–90 days from pellet/sham implantation) after 10 hour fast (n = 8 rats in DHT and DHT+ liraglutide group and n = 5 in control group). * denotes p<0.05 between DHT and DHT+ liraglutide and DHT and control.</p

Effect of liraglutide on DHT induced perturbed blood pressure parameters.

<p>(Mean± SEM; mmHg)<b>:</b> a) Day time radiotelemeter data starting at 14 weeks of age: Data is averaged hourly over 15 days. Line graph depicts diastolic blood pressure (DBP; mmHg) (panel A), systolic blood pressure (SBP) (panel <i>B</i>), mean arterial pressure (MAP; mmHg) (panel <i>C</i>), and heart rate (HR; beats/min) (panel <i>D</i>), respectively b) Night time radiotelemeter data starting at 14 weeks of age: Data is averaged hourly over 15 days. Line graph depicts diastolic blood pressure (DBP; mmHg) (panel A), systolic blood pressure (SBP) (panel <i>B</i>), mean arterial pressure (MAP; mmHg) (panel <i>C</i>), heart rate (HR; beats/min) (panel <i>D</i>), respectively. Bar graphs depict average values of BP parameters shown in panels A-D. Significant difference (p<0.05) between groups is marked as follows: # = DHT vs DHT+ liraglutide @ = DHT vs control.</p

Effect of liraglutide on abdominal fat in DHT treated rats.

<p>(Mean± SEM; g): Abdominal fat was collected at end of study (88–90 days from pellet/sham implantation) in control (n = 8), DHT (n = 11) and DHT+Liraglutide (n = 8). * denotes p<0.05 between DHT + liraglutide and DHT and control.</p