Sub link: Functional Properties of X and Y Sperm
Sub Link: Exposure to Environmental Factors
Sub Link: Take Home Message

The short answer is, we are not yet certain why X-to-Y sperm ratios differ so greatly between individuals. Several factors, particularly genetic and environmental factors, may differentially affect the ratio of X and Y sperm that an individual produces by making one sperm type more sensitive to external stress than the other. However, this view is based on theories without conclusive evidence. A few of these theories are described below (references follow the list below).

• An unidentified gene may control the ratio of X and Y spermatozoa such that men with more brothers have a higher probability of having sons, and those with more sisters have a higher probability of having daughters.

• An active gene transcription may lead to modifications in the differential survival of spermatozoa during epididymal maturation, and these may alter the expected ratio.

• An in vitro ligand activation may significantly suppress the motility of X sperm, thus producing more than 90% male embryos following fertilization. In a knockout mouse model, partial deletions of the Y chromosome were reported that might skew the offspring sex ratio.

• A complete deletion of the X-linked Slxl1 gene may produce more male offspring by regulating the transition of post-meiotic germ cells.

• An increased incidence of Y aneuploidy in spermatozoa may selectively eliminate the Y sperm, thus increasing the X sperm in mice and humans.

• The viability of human Y sperm may be lower than that of X sperm under in vitro stressful conditions, which may lead to shifts in the Y-to-X ratio.

Functional Properties of X and Y Sperm

These findings indicate that functional properties of X and Y sperm differ under certain in vivo or in vitro conditions, due to the transcription of specific genes in particular cell types subsequently leading to the altered sex ratio at birth.

References:

• Gellatly, C. Trends in Population Sex Ratios May be Explained by Changes in the Frequencies of Polymorphic Alleles of a Sex Ratio Gene. Evol Biol 36, 190–200 (2009). 

• Bean, B. (1990). Progenitive sex ratio among functioning sperm cells. Am. J. Hum. Genet. 47, 351–353.

• Hu, Y. C., and Namekawa, S. H. (2015). Functional significance of the sex chromosomes during spermatogenesis. Reproduction 149, R265–R277. doi: 10. 1530/REP-14-0613

• Umehara, T., Tsujita, N., and Shimada, M. (2019). Activation of Toll-like receptor 7/8 encoded by the X chromosome alters sperm motility and provides a novel simple technology for sexing sperm. PLoS Biol. 17:e3000398. doi: 10.1371/ journal.pbio.3000398

• Rathje, C. C., Johnson, E. E. P., Drage, D., Patinioti, C., Silvestri, G., Affara, N. A., et al. (2019). Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution. Curr. Biol. 29, 3692–3698.e4. doi: 10.1016/j. cub.2019.09.031

• Kruger, A. N., Brogley, M. A., Huizinga, J. L., Kidd, J. M., de Rooij, D. G., Hu, Y. C., et al. (2019). A neofunctionalized X-linked ampliconic gene family is essential for male fertility and equal sex ratio in mice. Curr. Biol. 29, 3699–3706.e5. doi: 10.1016/j.cub.2019.08.057

• Chaudhary, I., Jain, M., and Halder, A. (2014). Sperm sex ratio (X: Y ratio) and its variations. Austin J. Reprod. Med. Infertil. 1:7.

• You, Y. A., Kwon, W. S., Saidur Rahman, M., Park, Y. J., Kim, Y. J., and Pang, M. G. (2017). Sex chromosome-dependent differential viability of human spermatozoa during prolonged incubation. Hum. Reprod. 32, 1183–1191. doi: 10.1093/humrep/dex080.

Exposure to Environmental Factors

There are numerous reports of a decrease in the male:female birth ratio in many countries over the past fifty years, theorized to be due to exposure to environmental factors. The publications below delve into this topic.

References:

• Allan, BB, Brant, R, Seidel, JE, and Jarrell, JF. (1997). Declining sex ratios in Canada. Canadian Medical Association Journal, 156(1), 37–41.

• van der Pal-de Bruin, KM, Verloove-Vanhorick, SP, and Roeleveld, N. (1997). Change in male: Female ratio among newborn babies in Netherlands. The Lancet, 349(9044), 62.

• Marcus, M., Kiely, J., Xu, F., McGeehin, M., Jackson, R., and Sinks, T. (1998). Changing sex ratio in the United States, 1969–1995. Fertility and Sterility, 70(2), 270–273.

• Møller, H. (1998). Trends in sex-ratio, testicular cancer and male reproductive hazards: Are they connected? Acta Pathologica, Microbiologica et Immunologica Scandinavica, 106(1–6), 232–238.

• Parazzini, F., La Vecchia, C., Levi, F., and Franceschi, S. (1998). Trends in male:female ratio among newborn infants in 29 countries from five continents. Human Reproduction, 13(5), 1394–1396.

Among the leading candidates for this decrease are theorized to be exposure to endocrine-disrupting compounds and various air pollutants, as explored in the publications listed below.

References:

• Van Larebeke, NA., Sasco, AJ, Brophy, TJ, Keith, MM, Gilbertson M, and Watterson, A (2008). Sex ratio changes as sentinel health events of endocrine disruption. International Journal of Occupational and Environmental Health, 14(2), 138–143.

• Davis, DL, Gottlieb, MB, and Stampnitzky, JR. (1998). Reduced ratio of male to female births in several industrial countries- a sentinel health indicators? Journal of the American Medical Association, 279(13), 1018–1023.

• Radwan, M, Dziewirska E, Radwan P, Jakubowski L, Hanke W, and Jurewicz J. Air Pollution and Human Sperm Sex Ratio. American Journal of Men’s Health 2018, Vol. 12(4) 907–912.

Take Home Message

Therefore, genetic and environmental factors or both may differentially affect the ratio of sex bearing sperm by making one sperm type more sensitive to loss or degradation than that of the other, thus confirming the possibility of disparity between the percentage of X- and Y-bearing sperm in an ejaculate.