Sperm Physiological Response to Female Serum—Potential New Insights into the Reproductive Incompatibility Diagnostics

Infertility is assumed to arise exclusively from male- and female-dependent pathological factors. However, recent studies have indicated that reproductive failure may also result from the reproductive incompatibility of the partners. Selection against such incompatibilities likely occurs via female-derived reproductive secretions, including follicular fluid (FF), that mediate gamete-level mate choice towards the sperm of specific males. To facilitate potential development of diagnostic tests for human reproductive incompatibility, we examined whether sperm physiological response to female serum indicate male–female compatibility in the presence of FF. We performed a full-factorial experiment, in which the sperm of 10 males were treated with the FF and serum of 6 healthy females. We found that sperm motility and viability in both biofluids were highly similar and that in 70% of the males, sperm serum treatment predicted male–female compatibility. We also identified male human leucocyte antigen (HLA) alleles and female (FF and serum) anti-HLA antibodies and tested whether the number of allele–antibody matches predict sperm physiological response to female fluids. However, no association was found between measured sperm traits and the number of allele–antibody matches. Overall, the present results may open novel possibilities for the future development of reproductive incompatibility tests and may pave the way towards more accurate infertility diagnostics and treatments.

[1]  J. Kekäläinen Genetic incompatibility of the reproductive partners: an evolutionary perspective on infertility , 2021, Human reproduction.

[2]  J. Ramalho‐Santos,et al.  The impact of antisperm antibodies on human male reproductive function: an update. , 2021, Reproduction.

[3]  M. Magris,et al.  Structural dissimilarity of partners' immune genes increases sperm viability in women's reproductive tract , 2021, Journal of evolutionary biology.

[4]  C. Matás,et al.  Selection of Boar Sperm by Reproductive Biofluids as Chemoattractants , 2020, Animals : an open access journal from MDPI.

[5]  M. Magris,et al.  Post-copulatory genetic matchmaking: HLA-dependent effects of cervical mucus on human sperm function , 2020, Proceedings of the Royal Society B.

[6]  J. Kekäläinen,et al.  Gamete-level immunogenetic incompatibility in humans–towards deeper understanding of fertilization and infertility? , 2020, Heredity.

[7]  J. Fitzpatrick,et al.  Chemical signals from eggs facilitate cryptic female choice in humans , 2020, Proceedings of the Royal Society B.

[8]  J. Partanen,et al.  Increasing accuracy of HLA imputation by a population-specific reference panel in a FinnGen biobank cohort , 2020, NAR genomics and bioinformatics.

[9]  Ze Wu,et al.  Serum and follicular fluid thyroid hormone levels and assisted reproductive technology outcomes , 2019, Reproductive Biology and Endocrinology.

[10]  A. Rezaei,et al.  The expression of human leukocyte antigen by human ejaculated spermatozoa , 2019, Molecular genetics & genomic medicine.

[11]  H. Hollema,et al.  The Origin of Follicular Bile Acids in the Human Ovary. , 2019, The American journal of pathology.

[12]  He-min Zhang,et al.  Reproductive Strategy Inferred from Major Histocompatibility Complex-Based Inter-Individual, Sperm-Egg, and Mother-Fetus Recognitions in Giant Pandas (Ailuropoda melanoleuca) , 2019, Cells.

[13]  M. Milinski,et al.  Cryptic haplotype‐specific gamete selection yields offspring with optimal MHC immune genes , 2018, Evolution; international journal of organic evolution.

[14]  J. Kekäläinen,et al.  Gamete-mediated mate choice: towards a more inclusive view of sexual selection , 2018, Proceedings of the Royal Society B: Biological Sciences.

[15]  Per B. Brockhoff,et al.  lmerTest Package: Tests in Linear Mixed Effects Models , 2017 .

[16]  Casper W. Berg,et al.  glmmTMB Balances Speed and Flexibility Among Packages for Zero-inflated Generalized Linear Mixed Modeling , 2017, R J..

[17]  Niels Jørgensen,et al.  Temporal trends in sperm count: a systematic review and meta-regression analysis , 2017, Human reproduction update.

[18]  Sean G Brown,et al.  Complex CatSper-dependent and independent [Ca2+]i signalling in human spermatozoa induced by follicular fluid , 2017, Human reproduction.

[19]  R. C. Firman,et al.  Postmating Female Control: 20 Years of Cryptic Female Choice , 2017, Trends in ecology & evolution.

[20]  J. Kekäläinen,et al.  Female‐induced remote regulation of sperm physiology may provide opportunities for gamete‐level mate choice , 2017, Evolution; international journal of organic evolution.

[21]  J. Havlíček,et al.  Patterns of MHC‐dependent mate selection in humans and nonhuman primates: a meta‐analysis , 2017, Molecular ecology.

[22]  S. Marsh-Rollo,et al.  Ovarian fluid allows directional cryptic female choice despite external fertilization , 2016, Nature Communications.

[23]  R. Montgomerie,et al.  Cryptic female choice enhances fertilization success and embryo survival in chinook salmon , 2016, Proceedings of the Royal Society B: Biological Sciences.

[24]  B. Jaiswal,et al.  Sperm Motility Regulatory Proteins: A Tool to Enhance Sperm Quality , 2016 .

[25]  T. Laskemoen,et al.  Sperm performance in conspecific and heterospecific female fluid , 2016, Ecology and evolution.

[26]  C. Becker,et al.  Characterization of the Olfactory Receptors Expressed in Human Spermatozoa , 2016, Front. Mol. Biosci..

[27]  J. Kekäläinen,et al.  Lectin staining and flow cytometry reveals female-induced sperm acrosome reaction and surface carbohydrate reorganization , 2015, Scientific Reports.

[28]  Nicolas Garrido,et al.  Sperm selection in natural conception: what can we learn from Mother Nature to improve assisted reproduction outcomes? , 2015, Human reproduction update.

[29]  A. Pilastro,et al.  Major histocompatibility complex similarity and sexual selection: different does not always mean attractive , 2015, Molecular ecology.

[30]  Xavier A. Harrison,et al.  A comparison of observation-level random effect and Beta-Binomial models for modelling overdispersion in Binomial data in ecology & evolution , 2015, PeerJ.

[31]  W. Holt,et al.  Do sperm possess a molecular passport? Mechanistic insights into sperm selection in the female reproductive tract. , 2015, Molecular human reproduction.

[32]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[33]  D. Richardson,et al.  Cryptic female choice favours sperm from major histocompatibility complex-dissimilar males , 2013, Proceedings of the Royal Society B: Biological Sciences.

[34]  B S Weir,et al.  HIBAG—HLA genotype imputation with attribute bagging , 2013, The Pharmacogenomics Journal.

[35]  Shinichi Nakagawa,et al.  A general and simple method for obtaining R2 from generalized linear mixed‐effects models , 2013 .

[36]  R. Homburg,et al.  Unexplained infertility: an update and review of practice. , 2012, Reproductive biomedicine online.

[37]  A. Pilastro,et al.  Cryptic female preference for genetically unrelated males is mediated by ovarian fluid in the guppy , 2011, Proceedings of the Royal Society B: Biological Sciences.

[38]  O. Christiansen,et al.  The presence of HLA-antibodies in recurrent miscarriage patients is associated with a reduced chance of a live birth. , 2010, Journal of reproductive immunology.

[39]  Sanford Weisberg,et al.  An R Companion to Applied Regression , 2010 .

[40]  R. Rodgers,et al.  Morphological classification of bovine ovarian follicles. , 2010, Reproduction.

[41]  Manabu Yoshida,et al.  Control of sperm motility and fertility: Diverse factors and common mechanisms , 2008, Cellular and Molecular Life Sciences.

[42]  P. Stone,et al.  Antiphospholipid antibodies in serum and follicular fluid--is there a correlation with IVF implantation failure? , 2007, Human reproduction.

[43]  A. Dorfmann,et al.  Human follicular fluid-induced acrosome reaction predicts sperm fertilizing ability in vitro , 2007 .

[44]  M. Mandal,et al.  Identification and characterization of a sperm motility promoting glycoprotein from buffalo blood serum , 2006, Journal of cellular physiology.

[45]  J. Dudenhausen,et al.  Peptide and protein profiles in serum and follicular fluid of women undergoing IVF. , 2006, Human reproduction.

[46]  M. Eisenbach,et al.  Sperm guidance in mammals — an unpaved road to the egg , 2006, Nature Reviews Molecular Cell Biology.

[47]  I. Stefanidis,et al.  Serum and follicular fluid leptin levels are correlated with human embryo quality. , 2005, Reproduction.

[48]  S. Robertson Seminal plasma and male factor signalling in the female reproductive tract , 2005, Cell and Tissue Research.

[49]  E. Girsh,et al.  Human sperm chemotaxis: both the oocyte and its surrounding cumulus cells secrete sperm chemoattractants. , 2005, Human reproduction.

[50]  F. Schweigert,et al.  Concentrations of carotenoids, retinol and alpha-tocopherol in plasma and follicular fluid of women undergoing IVF. , 2003, Human reproduction.

[51]  L. Knapp,et al.  Human reproductive failure I: immunological factors. , 2001, Human reproduction update.

[52]  R. Paradisi, S. Neri, A. Pession, E. Magrini, E. B HUMAN LEUKOCYTE ANTIGEN II EXPRESSION IN SPERM CELLS: COMPARISON BETWEEN FERTILE AND INFERTILE MEN , 2000 .

[53]  V. Kay,et al.  Hyperactivated motility of human spermatozoa: a review of physiological function and application in assisted reproduction. , 1998, Human reproduction update.

[54]  W. J. Larsen,et al.  The ovarian blood follicle barrier is both charge- and size-selective in mice. , 1998, Biology of reproduction.

[55]  W. Eberhard Female control : sexual selection by cryptic female choice , 1996 .

[56]  T. Rülicke,et al.  Non-random fertilization in mice correlates with the MHC and something else , 1996, Heredity.

[57]  A. Arnaiz-Villena,et al.  Diploid expression of human leukocyte antigen class I and class II molecules on spermatozoa and their cyclic inverse correlation with inhibin concentration. , 1996, Biology of reproduction.

[58]  H. Janssen,et al.  Human serum and follicular fluid stimulate hyperactivation of human spermatozoa after preincubation. , 1994, Fertility and sterility.

[59]  Y. Wei,et al.  Antithrombin III enhances the motility and chemotaxis of boar sperm. , 1994, Comparative biochemistry and physiology. Comparative physiology.

[60]  F. Rodríguez,et al.  Lack of Expression of HLA Antigens on Immature Germ Cells From Ejaculates With Antisperm Antibodies , 1993, American journal of reproductive immunology.

[61]  D. Garbers,et al.  SPERM ATTRACTION TO A FOLLICULAR FACTOR(S) CORRELATES WITH HUMAN EGG FERTILIZABILITY , 1991 .

[62]  G. Clarke,et al.  Sperm Antibodies, Immunoglobulins, and Complement in Human Follicular Fluid , 1984, American journal of reproductive immunology : AJRI : official journal of the American Society for the Immunology of Reproduction and the International Coordination Committee for Immunology of Reproduction.

[63]  A. Menge,et al.  Immunologic studies on human follicular fluid. , 1971, Fertility and sterility.

[64]  A. Lenzi,et al.  Genetic and molecular diagnostics of male infertility in the clinical practice. , 2014, Frontiers in bioscience.

[65]  C. Cheng,et al.  The blood-follicle barrier (BFB) in disease and in ovarian function. , 2012, Advances in experimental medicine and biology.

[66]  Organización Mundial de la Salud WHO laboratory manual for the examination and processing of human semen , 2010 .

[67]  J. Aguilar,et al.  The uterine tubal fluid: secretion, composition and biological effects , 2005 .