母體果糖暴露程式化子代成鼠產生代謝症相關之膀胱過動
李偉嘉1 田祐霖2,3 呂史提3 吳俐慧3 華瑜3
高雄長庚紀念醫院泌尿科1，兒科部2，轉譯中心3
Maternal fructose exposure programs metabolic syndrome-associated bladder overactivity in young adult offspring
Wei-Chia Lee, M.D. Ph.D.1, You-Lin Tain, M.D. Ph.D.2,3, Steve Leu, Ph.D.3,
Kay L.H. Wu, Ph.D.3, Julie Y.H. Chan. Ph.D.3*
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Division of Urology1, Department of pediatrics2,
Institute for Translational Research in Biomedicine3
Purpose: To investigate effects of MFE on developmental programming of MetS-associated bladder dysfunction and identify potential transcripts involved in the programmed bladder overactivity in adult offspring.
Materials and Methods: Pregnant Sprague-Dawley rats received a fructose-enriched or control diet during pregnancy and lactation. Male offspring were studied for the phenotypes of MetS and voiding behavior at the age of 12 week. Next-generation sequencing and qPCR were used to screen and validate transcript alterations in rat bladders. In vivo cystometry and in vitro detrusor contractility were used to evaluate bladder function. Bladder tissues were obtained for Western blotting of postsynaptic receptors.
Results: Compared to controls, MFE offspring showed bladder overactivity and traits of MetS. Alterations in bladder transcripts, including increased mRNA levels of M2- and M3-mAChR, P2X1 receptor, and VPAC2 receptor and decreased mRNA levels of TRPV4 receptor, were found in MFE offspring. Significantly decreased carbachol-induced contractility combined with upregulation of M2- and M3-mAChR receptors and P2X1 receptor proteins of the bladder were noted in MFE offspring.
Conclusions: Our data show MFE can program MetS-associated bladder overactivity in young adult male offspring. Alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression, may be associated with primary or secondary programmed bladder dysfunction in MFE offspring. Decreased carbachol-induced contractility, along with upregulation of M2- and M3-muscarinic receptors and P2X1 receptor protein expression in the bladder, may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE.