Discipline of Human Physiology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Private Bag X54001, Durban 4000, South Africa.
Life Sci. 2021 Apr 15;271:119179. doi: 10.1016/j.lfs.2021.119179. Epub 2021 Feb 9.
Male infertility and reproductive dysfunctions have become major global health problems. Although several causative factors have been attributed to this challenge, of importance are alterations in maternal-foetal environment, diet-induced transcriptional changes and dysregulation in chemical signaling via hypothalamic-gonadal axis.
The present study investigated the impact of maternal high-fat diet (HFD) consumption and the putative role of Quercetin-3-O-rutinoside on reproductive functions of male offspring rats at critical developmental stages with a quest to unravel the underpinned molecular changes.
Fifty-six pregnant rats (previously fed normal diet ND) or 45% HFD) were maintained on supplemented chow (150 mg/kg QR) - ND/QR, HFD/QR throughout gestation. Subsequently, dams (n = 7) and offspring (n = 6) were sacrificed at post-natal day (PND) 21, 28 and 35, respectively, and the blood, placenta, hypothalamus (HT), and testicular samples were processed for molecular analysis of Gonadotropin-releasing hormone (GnRH), Luteinizing hormone (LH), testosterone, chemerin, chemokine-like receptor 1 (CMKLR1), tumour necrosis factor α (TNF-α), interleukin 1β (IL-1β) and nuclear factor kappa B (NF-κB).
We observed a significant decrease in GnRH level in the HFD group at PND21 and PND28 in male offspring and treatment with QR significantly reduced GnRH. There was a significant reduction in LH levels in the HFD group at PND 21 in the male offspring accompanied by a significant decrease in testosterone level at PND 28 and PND35 which appears to be age dependent. In the HT, Chemerin and CMKLR1 was significantly upregulated in the HFD group at PND 21 and PND 35 respectively while CMKLR1 was significantly downregulated in the HFD group of the placenta and testis at PND 21. TNF-α, IL-1β and NF-κB were also expressed in the placenta, HT and testis at PND 21.
Male fertility is affected by maternal HFD consumption while chemerin, CMKLR1 and TNF-α, may play a significant role in male steroidogenesis. Treatment with QR had little or no ameliorative effect on HFD induced alterations in male reproductive functions.
男性不育和生殖功能障碍已成为全球主要的健康问题。尽管有几个致病因素与此挑战有关，但重要的是母体-胎儿环境的改变、饮食诱导的转录变化以及通过下丘脑-性腺轴的化学信号失调。
本研究旨在探讨母体高脂肪饮食（HFD）摄入的影响，以及槲皮素-3-O-芸香糖苷（Quercetin-3-O-rutinoside，QR）对雄性仔鼠生殖功能的潜在作用，在关键发育阶段研究其作用，以揭示潜在的分子变化。
56 只怀孕大鼠（之前喂食正常饮食 ND）或 45% HFD）在整个妊娠期内维持在补充饲料（150mg/kg QR）-ND/QR、HFD/QR 上。随后，分别在产后第 21、28 和 35 天（PND）处死母鼠（n=7）和仔鼠（n=6），并对血液、胎盘、下丘脑（HT）和睾丸组织进行分析，以研究促性腺激素释放激素（GnRH）、黄体生成素（LH）、睾酮、趋化素、趋化素样受体 1（CMKLR1）、肿瘤坏死因子 α（TNF-α）、白细胞介素 1β（IL-1β）和核因子 kappa B（NF-κB）的分子变化。
我们观察到，雄性仔鼠在 PND21 和 PND28 时，HFD 组 GnRH 水平显著降低，而 QR 处理显著降低了 GnRH。在雄性仔鼠中，HFD 组在 PND21 时 LH 水平显著降低，同时在 PND28 和 PND35 时睾酮水平显著降低，这似乎与年龄有关。在 HT 中，HFD 组在 PND21 和 PND35 时 Chemerin 和 CMKLR1 显著上调，而在 PND21 时 HFD 组胎盘和睾丸中的 CMKLR1 显著下调。TNF-α、IL-1β 和 NF-κB 也在 PND21 时胎盘、HT 和睾丸中表达。
雄性生育能力受到母体 HFD 摄入的影响，而 Chemerin、CMKLR1 和 TNF-α 可能在雄性类固醇生成中发挥重要作用。QR 处理对 HFD 诱导的雄性生殖功能改变几乎没有或没有改善作用。
