The Robinson Institute and School of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, SA 5005, Australia.
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2200-5. doi: 10.1073/pnas.1305609111. Epub 2014 Jan 27.
Paternal characteristics and exposures influence physiology and disease risks in progeny, but the mechanisms are mostly unknown. Seminal fluid, which affects female reproductive tract gene expression as well as sperm survival and integrity, provides one potential pathway. We evaluated in mice the consequences for offspring of ablating the plasma fraction of seminal fluid by surgical excision of the seminal vesicle gland. Conception was substantially impaired and, when pregnancy did occur, placental hypertrophy was evident in late gestation. After birth, the growth trajectory and metabolic parameters of progeny were altered, most profoundly in males, which exhibited obesity, distorted metabolic hormones, reduced glucose tolerance, and hypertension. Altered offspring phenotype was partly attributable to sperm damage and partly to an effect of seminal fluid deficiency on the female tract, because increased adiposity was also evident in adult male progeny when normal two-cell embryos were transferred to females mated with seminal vesicle-excised males. Moreover, embryos developed in female tracts not exposed to seminal plasma were abnormal from the early cleavage stages, but culture in vitro partly alleviated this. Absence of seminal plasma was accompanied by down-regulation of the embryotrophic factors Lif, Csf2, Il6, and Egf and up-regulation of the apoptosis-inducing factor Trail in the oviduct. These findings show that paternal seminal fluid composition affects the growth and health of male offspring, and reveal that its impact on the periconception environment involves not only sperm protection but also indirect effects on preimplantation embryos via oviduct expression of embryotrophic cytokines.
父本特征和暴露因素会影响后代的生理和疾病风险，但其中的机制大多尚不清楚。精液会影响雌性生殖道基因表达以及精子的存活和完整性，这为其中一种潜在机制提供了线索。我们通过手术切除精囊腺来评估小鼠精液的血浆部分对后代的影响。这极大地损害了受孕能力，而且即使怀孕了，在妊娠后期也会出现胎盘肥大。出生后，后代的生长轨迹和代谢参数发生了改变，雄性最为明显，表现为肥胖、代谢激素紊乱、葡萄糖耐量降低和高血压。后代表型的改变部分归因于精子损伤，部分归因于精液缺乏对雌性生殖道的影响，因为当正常的二细胞胚胎被转移到与切除精囊的雄性交配的雌性体内时，雄性后代也表现出明显的肥胖。此外，即使胚胎在没有接触精液的雌性生殖道中发育，也会在早期卵裂阶段出现异常，但体外培养在一定程度上缓解了这种情况。缺乏精液伴随着胚胎营养因子 Lif、Csf2、Il6 和 Egf 的下调，以及卵卵管中凋亡诱导因子 Trail 的上调。这些发现表明，父本精液成分会影响雄性后代的生长和健康，并揭示了其对围孕期环境的影响不仅涉及精子保护，还通过卵卵管中胚胎营养细胞因子的表达对着床前胚胎产生间接影响。
