Post-copulatory genetic matchmaking: HLA-dependent effects of cervical mucus on human sperm function

Abstract

Several studies have demonstrated that women show pre-copulatory mating preferences for human leucocyte antigen (HLA)-dissimilar men. A fascinating, yet unexplored, possibility is that the ultimate mating bias towards HLA-dissimilar partners could occur after copulation, at the gamete level. Here, we explored this possibility by investigating whether the selection towards HLA-dissimilar partners occurs in the cervical mucus. After combining sperm and cervical mucus from multiple males and females (full factorial design), we found that sperm performance (swimming velocity, hyperactivation, and viability) was strongly influenced by the male-female combination. This indicates that sperm fertilization capability may be dependent on the compatibility between cervical mucus (female) and sperm (male). We also found that sperm viability was associated with partners' HLA dissimilarity, indicating that cervical mucus may selectively facilitate later gamete fusion between immunogenetically compatible partners. Together, these results provide novel insights into the female-mediated sperm selection (cryptic female choice) in humans and indicate that processes occurring after copulation may contribute to the mating bias towards HLA-dissimilar partners. Finally, by showing that sperm performance in cervical mucus is influenced by partners' genetic compatibility, the present findings may promote a deeper understanding of infertility.

Keywords: MHC; cervical mucus; cryptic female choice; genetic compatibility; infertility; sexual selection.

Figure 1.

The effect of male–female interaction (combination) on the proportion of hyperactivated sperm cells (calculated on four replicate measurements per combination ± s.e.) at three time points (60, 180, and 300 min) after the initiation of the cervical mucus treatment. Bar colours represent female identity (N = 9).

Figure 2.

The effect of male–female interaction (combination) on the proportion of live sperm cells (calculated on four replicate measurements per combination ± s.e.) in the cervical mucus. Bar colours represent female identity (N = 9).

Figure 3.

Sperm viability (proportion of live cells) was positively associated with male–female HLA dissimilarity. Datapoints represent fitted values obtained from the LMM. Male-specific associations are identified by different colours and the black line represents the average slope across all males. For each male–female combination, viability was determined based on two replicate measurements from each of the two sub-samples (n = 4 measurements in total, see ‘Material and Methods', for more details). The slope of the associations did not vary across males (p = 0.099).