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Developmental BiologybioRxiv
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Fetal programming by sodium saccharin and damage on male offspring reproductive

Alana Rezende GodoiiD, Vanessa Caroline Fioravante, Beatriz Melo Santos, Francisco Eduardo MartineziD, Patrícia Fernanda Felipe PinheiroiD

Abstract

Male infertility is responsible for 20-70% of infertility in couples. We investigated the effects of fetal programming with sodium saccharin consumption in testis structure and function and in male offspring fertility. Feed intake and efficiency, organ and fat weight, quantification and expression of AR and PCNA proteins, sperm count and hormonal dosages were performed. Changes in consumption were found in the final weeks of the experiment. Decreases in the expression and quantification of AR and PCNA, tubular diameter and luminal volume, and increase in epithelial and interstitial relative volumes were observed. Lower sperm count and transit and lower estradiol concentration were also found. The consumption of sodium saccharin by the dams programmed the male offspring affecting the HPG axis with alterations in Sertoli cell proliferation, AR expression and quantification, and sperm count. We hypothesize that these changes may be due to the reduction of estradiol that caused the loosening of the tight junctions of the blood-testis-barrier (BTB), causing cell losses during spermatogenesis, also reflecting, under the decrease in tubular diameter with an increase in epithelial volume and consequent decrease in luminal volume. Sodium saccharin programming directly affected the reproductive parameters of male offspring and adult fertility.

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