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.

Structural dissimilarity of partners' immune genes increases sperm viability in women's reproductive tract

“…Our results show that HLA eplet dissimilarity between partners positively affects sperm viability in follicular fluid, but not in cervical mucus. These findings are partly in contrast with previous results showing that male–female HLA allelic dissimilarity has a positive effect on sperm viability in cervical mucus (Jokiniemi, Magris, et al., 2020), but not in follicular fluid, although the association was marginally significant (Jokiniemi, Kuusipalo, et al., 2020). Whereas these previous studies have provided evidence for post‐copulatory selection based on partners' HLA dissimilarity, the exact molecular‐level mechanisms behind these findings have remained unclear.…”

“…The present study is based on two full‐factorial experiments (Jokiniemi, Kuusipalo, et al., 2020). In the first experiment, the sperm of eight males were treated with the follicular fluid of 10 women (Jokiniemi, Kuusipalo, et al., 2020), whereas in the second, the sperm of eight males were exposed to the diluted cervical mucus of nine females (Jokiniemi, Magris, et al., 2020). Six men and one woman participated in both experiments; that is, the total number of participants was 10 men and 18 women.…”

Evolutionary consequences of environmental effects on gamete performance

“…Similarly, female reproductive fluids (including ovarian fluid, follicular fluid, cervical mucus and egg jelly) can influence both gamete phenotypes and interactions between sperm and eggs [28][29][30][31]. The role of female reproductive fluids in chemotaxis to lead specific sperm cohorts to the eggs has been described first in broadcast-spawning marine invertebrates [32], but different forms of chemotaxis are also found in other taxa including fishes [33][34][35] and internal fertilizers such as mammals [36].…”

“…In internal fertilizers, paternal effects may be modulated by female responses [70,71]. Similarly, mate choice can occur at the gamete level [30,31,72]. These interactions between sperm and eggs may royalsocietypublishing.org/journal/rstb Phil.…”

“…B 376: 20200122 be modified by the environment in which they occur, such that poor performers in one environment are the best performers in another environment [67,73]. Hence, altered gamete environments may indirectly alter population traits via changes in the outcome of sperm competition [29] and gamete compatibility [30,31]. Consequently, gamete environments may play an important, yet under-appreciated role in shaping population responses to environmental change [9].…”