Evaluation of maternal high-fat diet and Quercetin-3-O-rutinoside treatment on the reproductive profile of diet naïve male offspring

Abstract

Background: 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.

Aim: 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.

Materials and methods: 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).

Key findings: 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.

Significance: 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.

Keywords: Adipokines; Developmental programming; High-fat diet; Male fertility; Pro-inflammatory cytokines; Sex hormones.