Department of Environmental and Biological Sciences, University of Eastern Finland, P.O. Box 111, FI-80101, Joensuu, Finland.
North Karelia Central Hospital, Tikkamäentie 16, FI-80210, Joensuu, Finland.
Heredity (Edinb). 2020 Nov;125(5):281-289. doi: 10.1038/s41437-020-0350-8. Epub 2020 Aug 3.
Human leukocyte antigen (HLA) immune genes play an important role in partner selection, but it has remained unclear if nonrandom pairing with respect to parental HLA genes could occur at the level of the gametes. We tested this possibility by investigating whether the sperm fertilization competence in humans is dependent on HLA genotype combination of the partners. We conducted a full-factorial experiment, in which the sperm physiological preparation for fertilization among multiple males was studied in the presence of follicular fluid (oocyte surrounding bioactive liquid) of several females. All the studied sperm pre-fertilization physiological parameters (motility, hyperactivation, acrosome reaction, and viability) were strongly dependent on male-female combination. In other words, follicular fluids (women) that induce strong sperm physiological response in some males often induce much weaker response in the other(s). Sperm physiological responses were stronger in HLA-dissimilar male-female pairs than in HLA-similar combinations, but none of the measured sperm traits were associated with genome-wide similarity. Together, these findings shed new light on the evolutionary and immunological mechanisms of fertilization. Furthermore, our results raise an intriguing possibility that against currently prevailing WHO's definition, infertility may not represent exclusively a pathological condition, but may also result from immunogenetic incompatibility of the gametes.
人类白细胞抗原 (HLA) 免疫基因在伴侣选择中起着重要作用，但关于配子水平上 HLA 基因是否存在非随机配对仍不清楚。我们通过研究人类精子受精能力是否取决于伴侣 HLA 基因型组合来检验这种可能性。我们进行了一项完全因子实验，研究了多个男性的精子在几个女性的卵泡液（卵周围的生物活性液体）存在下的受精前生理准备情况。所有研究的精子前受精生理参数（运动性、超活化、顶体反应和活力）都强烈依赖于男性-女性的组合。换句话说，在一些男性中诱导强烈精子生理反应的卵泡液（女性）在其他男性中往往诱导较弱的反应。HLA 不同的男性-女性对与 HLA 相似的组合相比，精子生理反应更强，但没有一项测量的精子特征与全基因组相似性相关。这些发现为受精的进化和免疫学机制提供了新的线索。此外，我们的结果提出了一个有趣的可能性，即与目前普遍接受的世卫组织的定义相反，不孕不育可能不仅仅代表一种病理状况，也可能是由于配子的免疫遗传不相容性。
