53, 407412. (2000). TLR7/8 ligands suppress the motility of X-containing sperm, indicating that this receptor can differentially affect sperm function on the basis of the sex chromosome they bear. 69, 347352. Does paternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) affect the sex ratio of offspring? J. Hum. Functional human sperm capacitation requires both bicarbonate-dependent PKA activation and down-regulation of Ser/Thr phosphatases by Src family kinases. doi: 10.1002/biot.200900211, Mocarelli, P., Gerthoux, P. M., Ferrari, E., Patterson, D. G. Jr., Kieszak, S. M., Brambilla, P., et al. Additional mechanism is coating sperm with surface molecules during epididymal maturation to make sperm look alike. Gynecol. Huntingtons disease in Greece: the experience of 14 years. Genet. Sex preselection methods can be divided into two general groups which either separate spermatozoa on the basis of subtle physical or kinetic features or those which rely on distinctive nuclear characteristics unique either to X or Y chromosome bearing sperm. Am. Anim. Mol. (2005). 17, 26002614. Krco, C. J., and Goldberg, E. H. (1976). 85, 121127. Thus, majority of the recent findings do not provide any logical explanation for X and Y spermatozoa acting differently at various pH conditions. Therefore, different methods of sperm enrichment might also influence the incidence of aneuploidy. Reprod. Indeed, differentiation between X and Y spermatozoa has been of immense interest to researchers, physicians, and breeders, since the beginning of recorded history. 20, 16881694. Chayko, C. A., and Martin-Deleon, P. A. Fertil. doi: 10.1016/0006-291x(84)91050-7. doi: 10.1073/pnas.0811895106. In addition, we have highlighted the proteomics and genomics aspects of both cells, and investigated their clinical significance, in order to predict whether this difference could explain the occurrence of particular diseases in a sex-specific-manner. A spermatozoa carrying a Nature has developed many mechanisms to make genetically different sperm phenotypically identical within a male to avoid a fertilization advantage of one allele over another. Some of these genes (particularly receptors) are also shown to be related to the growth, survivability, and functions of specific sperm types (Umehara et al., 2019). 110(Suppl. Prevalence and severity of anaemia stratified by age and gender in rural India. Spermatozoa contain a minute amount of total RNA (human spermatozoon, 0.015 pg; bovine spermatozoon, 1.8 104 pg) compared to that in the somatic cells (13 pg). Mol. Simultaneous detection of X- and Y-bearing human sperm by double fluorescence in situ hybridization. A comprehensive proteomic approach to identifying capacitation related proteins in boar spermatozoa. (2008). Identification and characterization of genes differentially expressed in X and Y sperm using suppression subtractive hybridization and cDNA microarray. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Acad. Epidemiological study revealed a significant association between exposure to two organochlorine chemicals and sex chromosome disomy in the spermatozoa collected from men who underwent infertility assessment at the Massachusetts General Hospital between January 2000 and May 2003 (Mcauliffe et al., 2012). (2019). Mol. doi: 10.1159/000472431. As such, it is also unclear whether X and Y spermatozoa vary in their shape and size. Mol. 25, 315318. Therefore, these cells are extremely suitable for performing proteomic analysis. doi: 10.1179/2049396714Y.0000000073, Meng, L., and Feldman, L. (2010). CA Cancer J. Clin. Differential sensitivity to reduction of the three beta subunit disulfide bonds. 8, 17331739. doi: 10.1093/molehr/3.6.545, Gharagozloo, P., and Aitken, R. J. Mol. Differential sperm motility mediates the sex ratio drive shaping mouse sex chromosome evolution. Certain preliminary studies reported several morphological differences between the X and Y spermatozoa using phase-contrast microscopy (Shettles, 1960; Cui and Matthews, 1993; Cui, 1997); however, most of the recent studies indicate that no major differences exist between the two sperm types (Hossain et al., 2001; You et al., 2017) except their DNA content. (2014). Urol. doi: 10.1016/j.anireprosci.2018.09.010, Shannon, M., and Handel, M. A. Health Perspect. Hum. 19, 570580. Reprod. Sperm counts and sperm sex ratio in male infertility patients. As an example, if Y spermatozoa move faster than X spermatozoa, a man should have a son, with an almost zero chance of having a daughter. J. Endocrinol. These diseases were also found to be associated with proteins that were highly expressed in X spermatozoa (Figure 2). Mol. Use of different proteomic approaches (i.e., 2DE-MS/MS, nUPLC-MS/MS, and SWATH-MS analysis) in these studies might have led to these differences. Biol. Sci. Hum. (2014) reported a non-significant difference while generating intracellular reactive oxygen species (ROS) by mitochondrial DNA in X and Y spermatozoa, and concluded that the tiny variations in DNA content between X and Y spermatozoa are unable to respond to stress differentially. 36, 190200. *Correspondence: Myung-Geol Pang, mgpang@cau.ac.kr, Editors Pick 2021: Highlights in Cell Growth and Division, View all Alminana et al. Hum. The oviduct as a complex mediator of mammalian sperm function and selection. Sex predetermination by separation of X and Y chromosome-bearing sperm: a review. 32, 11831191. Arch Androl 24, . Dev. doi: 10.1126/science.1108190, Aranha, I. P., and Martin-Deleon, P. A. Hum. Cytometry 35, 125128. A similar conclusion was drawn by other researchers (Ward and Coffey, 1991). Epigenetic transgenerational actions of endocrine disruptors and male fertility. Biophys. Reprod. Similar findings were obtained by other researchers by using several laboratory and domestic animal models (Silvers and Wachtel, 1977; Utsumi et al., 1993). J. Occup. Kruger, who works in the lab of principal investigator Jacob Mueller, Ph.D., and their colleagues have been studying the X and Y chromosomes -- which are delivered by sperm to an egg to determine . Mouse chromosome 6 in Rb translocations: consequences in singly and doubly heterozygous males. doi: 10.1017/s0021932000015467, Jasin, M., and Zalamea, P. (1992). Steril. doi: 10.1017/s0016672399004085, Templado, C., Bosch, M., and Benet, J. Anim. BMJ 332:916. (1983). Ann. Biol. (2019) reported that ligand activation of TLR7/8 significantly decreased the motility of X spermatozoa (by altering ATP production) than that of Y. Reprod. One way to achieve this goal is to use endonucleases to target repetitive sequences uniquely present within the X chromosome during male meiosis (the process driving the formation of the haploid gametes). Isolation of fractions rich in human Y sperm. 46, 678685. doi: 10.1016/s0140-6736(00)02290-x, Muehleis, P. M., and Long, S. Y. Immunol. (2015). Mol. Mol. doi: 10.1038/188916a0, Lankenau, S., Corces, V. G., and Lankenau, D. H. (1994). 47, 351353. It has been reported that an uncharacterized (unidentified) gene controlled the ratio of X and Y spermatozoa such that men with more brothers had a higher probability of having sons and those with more sisters had a higher probability of having daughters (Gellatly, 2009); however, these findings are mostly hypothetical, and presence of such a gene has not yet been confirmed. Sci. doi: 10.1371/journal.pone.0059387, Chandler, J. E., Steinholt-Chenevert, H. C., Adkinson, R. W., and Moser, E. B. This process was performed on the neat sample to establish the natural unchanged sperm sex-chromosome ratio (i.e. Human X- and Y-bearing sperm differ in cell surface sialic acid content. Wang, H. X., Flaherty, S. P., Swann, N. J., and Matthews, C. D. (1994). List of differentially expressed proteins in X and Y chromosome bearing spermatozoa. Fluorescent body distribution in spermatozoa in the male with exclusively female offspring. Cell Genet. Previous studies proposed a substantial difference between X and Y spermatozoa, however, recent studies suggest negligible or no differences between these spermatozoa with respect to ratio, shape and size, motility and swimming pattern, strength, electric charge, pH, stress response, and aneuploidy. H-Y antigen expression patterns in human X- and Y-chromosome-bearing spermatozoa. (1985). Sci. Mol. (1998) reported that the anti-HY antibody also binds to X spermatozoa and thus cannot be used to differentiate between X and Y spermatozoa. Of the 23 chromosomes in human spermatozoa, chromosomes 13, 18, 21, X, and Y are important because higher incidence of abnormalities in these chromosomes can to lead miscarriages or live births (Pang et al., 1999, 2005, 2010; Rubio et al., 2001). 45, 342350. 81, 908917. Parental age, parity and sex ratio in births in England and Wales, 1968-77. Selected References Reprod. These sperm were allowed to migrate into capillary tubes containing media of varying pH. Sex differences in renal cell cancer presentation and survival: an analysis of the National Cancer Database, 1993-2004. Repeated in utero and lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure affects male gonads in offspring, leading to sex ratio changes in F2 progeny. doi: 10.1038/sj.emboj.7601272, Blottner, S., Bostedt, H., Mewes, K., and Pitra, C. (1994). Natl. Eventually, by the process of several mitotic cell divisions, type Al spermatogonia become type B spermatogonia (Leblond and Clermont, 1952; Oakberg, 1956). doi: 10.1016/j.fertnstert.2005.07.1295, Zhu, J., Barratt, C. L., Lippes, J., Pacey, A. Health 14, 138143. After the hybridization, the probes were . Spriggs, E. L., Rademaker, A. W., and Martin, R. H. (1996). Reprod. Interestingly, men with higher serum levels of polychlorinated biphenyls (PCBs) presented a significant increase in the frequency of YY (Y sperm disomy), XY, and total sex chromosome disomy, however, this study did not provide further explanation of their findings, specifically on the mechanism by which the increased exposure to PCBs exerted protective effects against XX disomy and that in which the increased exposure to p,p-DDE increased XX disomy. Therefore, possible mechanism(s) underlying the association between exposure to toxic chemicals, including EDCs (for example PCBs and p, p-DDE), and sex chromosome disomy should be investigated. Hum. (2013). doi: 10.1038/186648a0, Shettles, L. B. Nature 188, 916918. This finding was partly supported by other investigators (De Canio et al., 2014; Scott et al., 2018). However, the direction of this deviation depends on whether a particular sequence is close to or far from the nearest gene. Functional significance of the sex chromosomes during spermatogenesis. Lifestyle, environment, and male reproductive health. It comprises autosomes and an X (X spermatozoa) or a Y chromosome (Y spermatozoa). A novel approach to assessing bisphenol-A hazards using an in vitro model system. Asian J. Androl. Subsequently mature spermatozoa are released in semen during ejaculation, and is capable of fertilizing an oocyte, followed by contributing half of the genetic material to the offspring (Clapham, 2013; Rahman et al., 2013). Veterinarmed. Hamamah, S., and Gatti, J. L. (1998). J. Exp. Reprod. 37, 362372. doi: 10.1016/s0015-0282(99)00279-4, Pratt, N. C., Huck, U. W., and Lisk, R. D. (1987). (2019). doi: 10.1530/REP-14-0613, Iizuka, R., Kaneko, S., Aoki, R., and Kobayashi, T. (1987). 75, 4047. A simpler way to choose the sex of offspring by separating X and Y sperm: Differential gene activity by the two sex chromosomes allows X-bearing sperm to be slowed down --. 65, 529. (1960). 120, 535540. Recent studies have reported alterations in the sex ratio of human offspring exposed to increased levels of environmental chemicals, specifically endocrine-disrupting chemicals (EDs) (Van Larebeke et al., 2008; Mcdonald et al., 2014; Song et al., 2018; You et al., 2018). Mol. (1975). doi: 10.1021/pr500524p, Kwon, W. S., Rahman, M. S., Lee, J. S., Yoon, S. J., Park, Y. J., and Pang, M. G. (2015). Enrichment of bovine X- and Y-chromosome-bearing sperm with monoclonal H-Y antibody-fluorescence-activated cell sorter. Hum. Mol. Detection of X- and Y-bearing human spermatozoa after motile sperm isolation by swim-up. This procedure allows producing over 90% of the male embryos following in vitro fertilization using ligand-selected highly motile spermatozoa. 124, 950955. The Sxr (sex-reversed) region that carries a copy of the mouse Y chromosomal testis-determining gene can be attached to the distal end of either the Y or the X chromosome. J. Obstet. Chem. There were no significant differences (P > 0.05) in the percentage of presumptive zygotes between the control and the X-sperm sorted group, but there was a difference in early cleaving embryos with there being 81.2 1.4%, 78.3 1.0%, and 66.7 1.1% for the control, X-sperm sorted, and Y-sperm sorted groups, respectively. 4:7109. doi: 10.3402/ehtj.v4i0.7109, Tesarik, J., and Mendoza, C. (1996). Evol. In a recent study, Umehara et al. Acad. During spermatogenesis, undifferentiated spermatogonia (stem cells) transform into type Al spermatogonia (differentiated cells). Analysis of meiotic segregation in human nondecondensed interphase spermatozoa by triple colour rapid direct fluorescent in situ hybridization. Reacting mouse sperm with monoclonal H-Y antibodies does not influence sex ratio of eggs fertilized in vitro. The ratio of X- and Y-bearing sperm in ejaculates of men with three or more children of the same sex A preponderance of either sons or daughters in a family cannot be explained simply by an altered ratio of X-bearing and Y-bearing sperm in the father's semen. Nevertheless, several researchers have suggested that the size of a sperm is not exclusively associated with its chromosomal content and may also be associated with its cytoplasmic content, which may vary in a specific sperm population during spermatogenesis (Shannon and Handel, 1993; Lankenau et al., 1994; Cui, 1997). (2001). Biol. (1985). Expression of the Hprt gene during spermatogenesis: implications for sex-chromosome inactivation. However, significant difference was observed in X/Y-sorted semen (93.3 0.08% X and 91.4 0.06% Y-sperm), as compared to the expected ratio in unsorted semen or the post-sorting reanalysis data. We used the Pathway Studio program and found that proteins that were highly expressed in X spermatozoa were significantly (P < 0.05) correlated with five major canonical pathways/signaling, whereas proteins that were highly expressed in Y spermatozoa were correlated with four pathways/signaling (Table 4). Int. 40, 205212. Prevalence of anemia in adult rural population of north India. Both the cancers are the leading cause of cancer deaths in women (Siegel et al., 2015). doi: 10.1016/s0015-0282(16)40330-4, Rahman, M. S., Kang, K. H., Arifuzzaman, S., Pang, W. K., Ryu, D. Y., Song, W. H., et al. In this section, we will compare X and Y spermatozoa based on their morphological and physiological characteristics. Sexing of human sperm by discontinuous Percoll density gradient and its clinical application. Here, we report evidence for the hypothesis that X and Y spermatozoa can be differentiated based on their surface HY antigen content. Determination of the parent of origin in nine cases of prenatally detected chromosome aberrations found after intracytoplasmic sperm injection. (2010). They observed that higher serum levels of p,p-dichlorodiphenyldichloroethylene (p,p-DDE) significantly increased the frequency of XX (X sperm disomy), XY, and total sex chromosome disomy. Dev. (1993). Mol. doi: 10.1093/toxsci/kfi066, Yan, J., Feng, H. L., Chen, Z. J., Hu, J., Gao, X., and Qin, Y. Multi-factorial influences on sex ratio: a spatio-temporal investigation of endocrine disruptor pollution and neighborhood stress. 80, 2932. Through the first meiotic cell division, the primary spermatocyte yields two secondary spermatocytes, which then enter the second meiotic division and divides into four round spermatids that contain either the X or Y chromosomes (Leblond and Clermont, 1952). Therefore, further studies are warranted to identify the genes expressed in the sexed spermatozoa of different species. Sex ratio variation between ejaculates within sire evaluated by polymerase chain reaction, calving, and farrowing records. 198, 121128. It is a fundamental part of the membrane of most male cells and is a specific antigen that controls the Y sperm-specific genes (Ohno and Wachtel, 1978). Eur. Epididymal epithelium secretes sialic acid (glycoprotein) that provides a net negative surface charge to the spermatozoa (Hoffmann and Killian, 1981). Therefore, it is tempting to speculate that no or non-significant differences exist in the shape and size of X and Y spermatozoa. Do X and Y spermatozoa differ in proteins? doi: 10.1073/pnas.0913843107, Bibbins, P. E. Jr., Lipshultz, L. I., Ward, J. (1996) reported a non-significant difference in the concentration of plasma membrane proteins in porcine X and Y spermatozoa. Abstract PIP: A study was undertaken to examine the influence of pH on the migration of X and Y sperm as observed in freshly ejaculated semen samples from human donors. For example, heart failure was found to be related with CAPZB that was highly expressed in Y spermatozoa, however, its incidence is lower in men than that in women. Limited studies have supported this preliminary hypothesis. Table 2. (2008). Steril. The secondary sex ratio in the United States 1969-71: association with race, parental ages, birth order, paternal education and legitimacy. Environ. Genet. Activation of Toll-like receptor 7/8 encoded by the X chromosome alters sperm motility and provides a novel simple technology for sexing sperm. (1993) reported higher incidence of disomy in the Y chromosome (YY, 0.11%) than that in the X chromosome (XX, 0.08%). Toxicol. Of these, the protein related to the embryo development (EF-hand domain-containing protein 1) was expressed abundantly in the Y spermatozoa, whereas majority of other detected proteins were abundant in the X spermatozoa. A spermatozoon is a male reproductive cell that is produced in testis by highly orchestrated processes called spermatogenesis and spermiogenesis.
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