Aileen F Keating and Adam J Watkins
Afsaneh Khoshkerdar, Ece Eryasar, Hannah L Morgan, and Adam J Watkins
Pregnancy represents a time of dramatic physiological adaptation by the mother in which dramatic changes in maternal cardiovascular, metabolic and immune systems occur. These adaptations, initiated from the earliest stages of gestation, are crucial for the implantation and continued development of the embryo, the establishment of the placenta and the growth of the fetus. Impairments in the normal adaptation of the maternal cardiovascular, metabolic and immune systems underlie the aetiology of gestational disorders such as preeclampsia and gestational diabetes. Studies have shown that the development of such gestational complications not only affects the well-being of the mother but also the short- and long-term health of her offspring. While the connection between maternal lifestyle factors and the development of gestational disorders such as preeclampsia and gestational diabetes has been studied in detail, the link between a father’s lifestyle and the well-being of the mother during pregnancy has received less attention. In this review, we will explore the evidence that a range of paternal factors, such as age and diet, at the time of conception can not only affect the development of his offspring, but also the well-being of the mother during pregnancy. In addition, we will examine the sperm- and seminal plasma-specific mechanisms that connect the health of the father with that of the mother and his offspring.
Adam J Watkins, Emma S Lucas, Stephanie Marfy-Smith, Nicola Bates, Susan J Kimber, and Tom P Fleming
Mammalian placentation is dependent upon the action of trophoblast cells at the time of implantation. Appropriate fetal growth, regulated by maternal nutrition and nutrient transport across the placenta, is a critical factor for adult offspring long-term health. We have demonstrated that a mouse maternal low-protein diet (LPD) fed exclusively during preimplantation development (Emb-LPD) increases offspring growth but programmes adult cardiovascular and metabolic disease. In this study, we investigate the impact of maternal nutrition on post-implantation trophoblast phenotype and fetal growth. Ectoplacental cone explants were isolated at day 8 of gestation from female mice fed either normal protein diet (NPD: 18% casein), LPD (9% casein) or Emb-LPD and cultured in vitro. We observed enhanced spreading and cell division within proliferative and secondary trophoblast giant cells (TGCs) emerging from explants isolated from LPD-fed females when compared with NPD and Emb-LPD explants after 24 and 48 h. Moreover, both LPD and Emb-LPD explants showed substantial expansion of TGC area during 24–48 h, not observed in NPD. No difference in invasive capacity was observed between treatments using Matrigel transwell migration assays. At day 17 of gestation, LPD- and Emb-LPD-fed conceptuses displayed smaller placentas and larger fetuses respectively, resulting in increased fetal:placental ratios in both groups compared with NPD conceptuses. Analysis of placental and yolk sac nutrient signalling within the mammalian target of rapamycin complex 1 pathway revealed similar levels of total and phosphorylated downstream targets across groups. These data demonstrate that early post-implantation embryos modify trophoblast phenotype to regulate fetal growth under conditions of poor maternal nutrition.
Hannah L Morgan, Isaac Ampong, Nader Eid, Charlène Rouillon, Helen R Griffiths, and Adam J Watkins
The link between male diet and sperm quality has received significant investigation. However, the impact diet and dietary supplements have on the testicular environment has been examined to a lesser extent. Here, we establish the impact of a sub-optimal low protein diet (LPD) on testicular morphology, apoptosis and serum fatty acid profiles. Furthermore, we define whether supplementing a LPD with specific methyl donors abrogates any detrimental effects of the LPD. Male C57BL6 mice were fed either a control normal protein diet (NPD; 18% protein; n = 8), an isocaloric LPD (LPD; 9% protein; n = 8) or an LPD supplemented with methyl donors (MD-LPD; choline chloride, betaine, methionine, folic acid, vitamin B12; n = 8) for a minimum of 7 weeks. Analysis of male serum fatty acid profiles by gas chromatography revealed elevated levels of saturated fatty acids and lower levels of mono- and polyunsaturated fatty acids in MD-LPD males when compared to NPD and/or LPD males. Testes of LPD males displayed larger seminiferous tubule cross section area when compared to NPD and MD-LPD males, while MD-LPD tubules displayed a larger luminal area. Furthermore, TUNNEL staining revealed LPD males possessed a reduced number of tubules positive for apoptosis, while gene expression analysis showed MD-LPD testes displayed decreased expression of the pro-apoptotic genes Bax, Csap1 and Fas when compared to NPD males. Finally, testes from MD-LPD males displayed a reduced telomere length but increased telomerase activity. These data reveal the significance of sub-optimal nutrition for paternal metabolic and reproductive physiology.