Systemic arterial hypertension but not IGF-I treatment stimulates cardiomyocyte enlargement in neonatal lambs. Wilburn AN, Giraud GD, Louey S, Morgan T, Gandhi N, Jonker SS. Am J Physiol Regul Integr Comp Physiol. 2018 Nov 1;315(5):R1038-R1048. doi: 10.1152/ajpregu.00198.2018.
IGF-1 is known, excitingly, to cause proliferation of myocytes in the fetal sheep heart. It would be easier to treat newborns known to have too few cardiomyocytes than it would to treat fetuses. In this study we found that IGF-1 unfortunately doesn't stimulate cardiomyocyte proliferation in the newborn sheep heart. We also found that systolic load fails to stimulate myocyte proliferation in the newborn, although unlike IGF-1 it does lead to cellular and cardiac hypertrophy. If we want to use IGF-1 to expand cardiac myocyte number, we need to administer it to the fetus or determine why newborn cardiac myocytes are unresponsive.
Cardiac myocyte proliferation and maturation near term is inhibited by early gestation maternal testosterone exposure. Jonker SS, Louey S, Roselli CE. Am J Physiol Heart Circ Physiol. 2018 Nov 1;315(5):H1393-H1401. doi: 10.1152/ajpheart.00314.2018.
Elevated maternal testosterone is a feature of polycystic ovarian syndrome (PCOS), a very common endocrine disordered suffered by millions of women. When women with PCOS become pregnant, their hormones can affect fetal development. We found that elevated maternal testosterone during specific weeks early in pregnancy led to fetal undergrowth. This caused fetuses near the time of birth to be small for gestational age. The cardiac myocytes of these fetuses, had less cell cycle activity and were immature. This may have consequences for offspring of women with polycystic ovarian syndrome. Critically, although the focus has been on negative effects to girls born to women with high testosterone, the male fetuses were equally affected. Could this account for previously unexplained cardiovascular risk in some men?
Functional adaptations of the coronary microcirculation to anaemia in fetal sheep. Jonker SS, Davis L, Soman D, Belcik JT, Davidson BP, Atkinson TM, Wilburn A, Louey S, Giraud GD, Lindner JR. J Physiol. 2016 Nov 1;594(21):6165-6174. doi: 10.1113/JP272696.
The fetal heart responds to chronic fetal anemia by increasing heart size, because the heart needs to pump more blood to deliver enough oxygen. Heart size increases in the anemic fetus because cardiac myocyte proliferation (cell division) increases, and those cells get bigger. But those more, bigger working cells need capillaries to bring them oxygen and remove their waste. How does the coronary circulation provide enough oxygen to the cardiac myocytes? We discovered it is by increasing capillary diameter and red blood cell flux rate! We want to know: is this unusual adaptation common in the fetus?
Endocrine and other physiologic modulators of perinatal cardiomyocyte endowment. Jonker SS, Louey S. J Endocrinol. 2016 Jan;228(1):R1-18. doi: 10.1530/JOE-15-0309.
We needed a one-stop reference for perinatal changes in hormones and other physiological factors in sheep, so we wrote it! We describe how hormones, nutrients, and hemodynamic factors change as term approaches in the fetus, and at birth. Many of the studies we referenced were seminal studies that are now in harder-to-find journals. We were honored that this review was in the top 10 downloaded articles for the year in Journal of Endocrinology.
Timing of cardiomyocyte growth, maturation, and attrition in perinatal sheep. Jonker SS, Louey S, Giraud GD, Thornburg KL, Faber JJ. FASEB J. 2015 Oct;29(10):4346-57. doi: 10.1096/fj.15-272013.
Information about how adverse intrauterine environments or hormonal disruptions change cardiac growth in the fetus is most useful if we also know what normal developmental profiles are like. Here we determined how cardiac myocytes grow and mature before and after birth. We studied cell cycle activity and cellular division, terminal differentiation and multinucleation, and changes in cell size. Among many other things, we found that cardiac myocyte number decreases immediately prior to birth in sheep.