Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice

Abstract

SignificanceParental health and diet at the time of conception determine the development and life-long disease risk of their offspring. While the association between poor maternal diet and offspring health is well established, the underlying mechanisms linking paternal diet with offspring health are poorly defined. Possible programming pathways include changes in testicular and sperm epigenetic regulation and status, seminal plasma composition, and maternal reproductive tract responses regulating early embryo development. In this study, we demonstrate that paternal low-protein diet induces sperm-DNA hypomethylation in conjunction with blunted female reproductive tract embryotrophic, immunological, and vascular remodeling responses. Furthermore, we identify sperm- and seminal plasma-specific programming effects of paternal diet with elevated offspring adiposity, metabolic dysfunction, and altered gut microbiota.

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice

“…Intact and vasectomized 8 week old C57BL/6 male mice (Harlan Ltd, Belton, UK) were maintained as described previously (Watkins et al . ). Briefly, males were fed either control normal protein diet (NPD; 18% casein; 16 intact and eight vasectomized males) or isocaloric low protein diet (LPD; 9% casein; 16 intact and eight vasectomized) for a period of 8–12 weeks to ensure all stages of spermatogenesis and spermiogenesis were exposed to the diets (Oakberg, ).…”

“…Diets were manufactured commercially (Special Dietary Services Ltd, Witham, UK) and their composition has been reported previously (Watkins et al . ).…”

“…Offspring were generated as described previously (Watkins et al . ). Briefly, virgin 8‐week‐old female C57BL/6 mice (Charles River, Harlow, UK) were superovulated by intraperitoneal injections of pregnant mare serum gonadotrophin (1 IU; Interve, Milton Keynes, UK) and human chorionic gonadotrophin (1 IU; Intervet).…”

“…Sperm were isolated from caudal epididymi NPD and LPD stud males as described previously (Watkins et al . ) and allowed to capacitate in pre‐warmed medium (135 m m NaCl, 5 m m KCl, 1 m m MgSO 4 , 2 m m CaCl 2 , 30 m m Hepes; supplemented freshly with 10 m m lactic acid, 1 m m sodium pyruvate, 20 mg mL –1 BSA, 25 m m NaHCO 3 ). Females were artificially inseminated 12 h post human chorionic gonadotrophin injection with ∼10 7 sperm and subsequently housed overnight with a vasectomized C57BL/6 male fed either NPD or LPD.…”

Parental effects of male alternative reproductive tactics (ARTs) on ARTs of haploid sons

“…However, most likely, sneakers and fighters differ in the composition of their seminal fluids, such as in proteins (Crean, Adler, & Bonduriansky, ; Crean, Kopps, & Bonduriansky, ; Immler, ). The composition of the seminal fluid is commonly condition‐dependent, as for example shown for fruit flies (Wigby et al, ), house flies (Martin‐Coello et al, ), ladybird beetles (Perry & Rowe, ), neriid flies (Crean et al, ) and house mice (Watkins et al, ). Thus far, parental effects mediated by seminal fluids have only been suggested for diplodiploid animals (Crean et al, ) where non‐genetic alterations in offspring phenotypes, which arise from zygotes, may be mediated by differences in both sperm and accompanying substances (but see Crean et al () for non‐genetic effects by previous mates excluding sperm itself in neriid flies).…”