Gomes Viviane C L, Beckers Kalie F, Crissman Kassandra R, Landry Camille A, Flanagan Juliet P, Awad Reham M, Piero Fabio Del, Liu Chin-Chi, Sones Jenny L
Department of Veterinary Clinical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.
Department of Pathobiological Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.
Front Physiol. 2023 Mar 23;14:1070426. doi: 10.3389/fphys.2023.1070426. eCollection 2023.
Preeclampsia (PE) is a devastating hypertensive disorder of pregnancy closely linked to obesity. Long-term adverse outcomes may occur in offspring from preeclamptic pregnancies. Accordingly, sex-specific changes in pubertal development have been described in children from preeclamptic women, but the underlying mechanisms remain vastly unexplored. Features of PE are spontaneously recapitulated by the blood pressure high subline 5 (BPH/5) mouse model, including obesity and dyslipidemia in females before and throughout pregnancy, superimposed hypertension from late gestation to parturition and fetal growth restriction. A sexually dimorphic cardiometabolic phenotype has been described in BPH/5 offspring: while females are hyperphagic, hyperleptinemic, and overweight, with increased reproductive white adipose tissue (rWAT), males have similar food intake, serum leptin concentration, body weight and rWAT mass as controls. Herein, pubertal development and adiposity were further investigated in BPH/5 progeny. Precocious onset of puberty occurs in BPH/5 females, but not in male offspring. When reaching adulthood, the obese BPH/5 females display hypoestrogenism and hyperandrogenism. Kisspeptins, a family of peptides closely linked to reproduction and metabolism, have been previously shown to induce lipolysis and inhibit adipogenesis. Interestingly, expression of kisspeptins (Kiss1) and their cognate receptor (Kiss1r) in the adipose tissue seem to be modulated by the sex steroid hormone milieu. To further understand the metabolic-reproductive crosstalk in the BPH/5 offspring, expression in male and female rWAT were investigated. Downregulation of occurs in BPH/5 females when compared to males. Interestingly, dietary weight loss attenuated circulating testosterone concentration and rWAT downregulation in BPH/5 females. Altogether, the studies demonstrate reproductive abnormalities in offspring gestated in a PE-like uterus, which appear to be closely associated to the sexually dimorphic metabolic phenotype of the BPH/5 mouse model.
子痫前期（PE）是一种与肥胖密切相关的严重妊娠高血压疾病。子痫前期妊娠的后代可能会出现长期不良后果。因此，已有研究描述了子痫前期女性所生儿童青春期发育的性别特异性变化，但其潜在机制仍有待深入探索。血压高亚系5（BPH/5）小鼠模型可自发重现PE的特征，包括雌性小鼠在妊娠前及整个妊娠期的肥胖和血脂异常、妊娠晚期至分娩时的叠加性高血压以及胎儿生长受限。BPH/5后代已被描述具有性别二态性的心脏代谢表型：雌性小鼠贪食、高瘦素血症且超重，生殖白色脂肪组织（rWAT）增加，而雄性小鼠的食物摄入量、血清瘦素浓度、体重和rWAT质量与对照组相似。在此，对BPH/5后代的青春期发育和肥胖情况进行了进一步研究。BPH/5雌性小鼠青春期提前开始，而雄性后代则未出现这种情况。成年后，肥胖的BPH/5雌性小鼠表现为雌激素缺乏和雄激素过多。 Kisspeptins是一类与生殖和代谢密切相关的肽，先前已被证明可诱导脂肪分解并抑制脂肪生成。有趣的是，脂肪组织中Kisspeptins（Kiss1）及其同源受体（Kiss1r）的表达似乎受性类固醇激素环境的调节。为了进一步了解BPH/5后代中代谢与生殖的相互作用，研究了雄性和雌性rWAT中的表达情况。与雄性相比，BPH/5雌性小鼠中的表达下调。有趣的是，饮食减重可降低BPH/5雌性小鼠的循环睾酮浓度并减轻rWAT下调。总之，这些研究表明，在类似PE的子宫中孕育的后代存在生殖异常，这似乎与BPH/5小鼠模型的性别二态性代谢表型密切相关。
