1 Definition of sex based on reproductive cells
2 Short title: Cell-based definition of sex
3 Zhongneng Xu*1, 2
4
5 * --corresponding author, [email protected]; [email protected]
6
7 1Department of Ecology, Jinan University, Guangzhou 510632, China; 2Department of
8 Aquatic Bioscience, GraduateSchool of Agricultural and Life Science, the University
9 of Tokyo, Tokyo 113-8657, Japan. 10 Abstract
11 Increasing evidence shows that sex in some organisms, including humans, is a
12 continuous spectrum and sometimes, sexual differences in the organs of an individual
13 are contradictory and affected by physiological, pathological, and environmental
14 factors. The current definition of sex is thus in question. The present study indicated
15 that the definition of sex based on individuals, especially in multicellular organisms, is
16 inappropriate because the essence of sex was to distinguish between reproductive
17 subjects and the unit of reproduction is not an individual but a gamete cell. A definition
18 of sex based on gamete cells was thus proposed, focusing on material contributions
19 to reproduction by gamete cells and the formation of totipotent cells. To make this
20 definition of sex compatible with current related knowledge systems, individual sex
21 based on the quantitative proportions of different germ cells was also defined. The
22 relationships between the cell-based definition of sex and sex determination, sex
23 differences, and gender equality were discussed.
24
25 Word count = 155
26 Keywords = definition of sex, germ cell, reproduction, sex determination, sex
27 differences 28 1 Introduction
29 “Sex" has two meanings, sexual reproduction and gender, and in the present
30 study it refers to the latter. There has been a long history since sex was taken as an
31 academic issue. In his famous work Politics, Aristotle describes in detail human beings
32 born with different sexes (Jowett, 1885). The struggle for sex competition and sex
33 equality in human society is arduous. A sexually mature animal can accurately identify
34 the opposite sex, start its pursuit, and initiate a mating offensive. Biologists and
35 sociologists often consider sex differences when conducting research. All these show
36 that sex is a biological, social, and philosophical issue. The starting point for these
37 questions is: What is sex? The answer seems to be a common sense that cannot be
38 questioned, but it is actually full of many possibilities and exceptions. Social laws,
39 moral standards, academic authorities, social organizations, and governments may
40 impede the researchers' further thoughts of breaking through the current definition of
41 sex. However, some objective problems are increasingly plaguing scientists’ and
42 ordinary people's views on sex. These include both biological problems, such as the
43 parasex phenomenon of somatic cells (Pontecorvo, 1956) and male parthenogenesis
44 of plants and animals (Davies, 1958; Li et al., 2018), and social problems, such as the
45 phenomenon of intersex and homosexuality. This has to make us think more deeply
46 again: What is sex?
47
48 2 Confusion of the current definition of sex
49 Sex is a vital feature of sexually reproductive organisms. It is relevant to the
50 study of biological phenomena and, more importantly, is one of the indexes in diverse
51 human management systems. The current definition of sex is based on individuals,
52 involving reproductive functions, reproductive systems, genetic markers, etc. (Purves
53 et al, 2000; Knox and Schacht, 2011; Stevenson and Waite, 2011) ， and some
54 researchers broadly viewed sex as the feature in mixing genetic materials from
55 different individuals to form new individuals (Colegrave, 2012). Why the unit of sex in
56 the current definition of sex is based on individual is unclear, but at least from the
57 perspective of human sensory perception, differences in the appearances of human 58 individuals, as well as many other species, can indicate differences in reproductive
59 function.
60 Individuals of single-cell organisms are cells, so the unit of sex in unicellular
61 organisms is both an individual and a cell. The situation of multicellular organisms,
62 which is focused in the present study, is complicated. Individuals of multicellular
63 organisms are usually identified as females, males, or hermaphrodites according to
64 organ differences, gamete production, and sex chromosomes. Perhaps sex glands are
65 the major indexes to anatomically discriminate between males and females, and
66 external genitalia are another suitable candidate that does not require a bio-assay,
67 especially from the perspectives of the layperson. However, hermaphroditic individuals
68 are found among dioecious species, and some dioecious species, including humans,
69 even exhibit a continuous spectrum of phenotypes between females and males,
70 especially in the cases of some genetic and chromosomal diseases (Blackless et al.,
71 2000; Matson et al, 2011; Ainsworth, 2015). Gonad primordia in embryos have the
72 plastic potential to develop into female gonads or male gonads (Wilhelm et al., 2007).
73 With respect to external genitalia, surgical operations can change the sex of human
74 individuals of both male-to-females and female-to-males (Dhejne et al., 2011). Other
75 organs also have sex differences, including the brain. The sex of the brains is a
76 contested issue in biology and social management, and the sex of the brain sometimes
77 contradicts the sex shown by sexual chromosomes, sexual glands, and external
78 genitalia (Rogers, 2002). In some societies, gender is decided by self-recognition, and
79 a difference between personally-recognized sex and phenotypic sex is acceptable.
80 Identifying sex by on the basis of sex chromosomes is increasingly questioned. The
81 phenomenon of sex chromosome mosaicism has been demonstrated, and cells from
82 male embryos can be detected in the blood of their mothers (Hotta and Benzer, 1972;
83 Erlebacher and Fisher, 2017). More perplexingly, under some conditions, e.g.,
84 biotechnological operations, stem cells in vitro can change into eggs and sperms
85 (Hayashi et al., 2012; Irie et al., 2015; Saitou and Miyauchi, 2016).
86 Obviously, it is not sex that is confused, but the definition of sex. The present
87 paper addresses a proposal to confirm a definition of sex based on the essentially 88 biological significance of sex.
89
90 3 The essential nature of sex
91 Sex is dependent on sexual reproduction. The significance of sex lies in the
92 biological process of reproduction, especially in the period of fertilization and zygote
93 development in eukaryotes. Unlike asexual reproduction, sexual reproduction involves
94 the melding of two gametes and the sharing of the genetic materials. This process is
95 believed to be beneficial to genetic diversity of offspring, although whether the genetic
96 diversity allows them to adapt to the environment is another question (Kondrashov,
97 1993; Gross, 1996; Otto and Whitton, 2000). During fertilization, the gametes must be
98 distinguished from each other. In primitive isogamous organisms, the gametes are
99 difficult to be distinguished. In these species, “mating type”, an analogue of “sex”, is
100 used to describe the different groups that can mate. For anisogamous organisms, sex
101 is used to distinguish the highly differentiated gametes. Zygotes receive not only
102 genetic materials but also nutrients and organelles from the gametes. Thus, the
103 concept of sex should carry information about the contribution of genetic materials,
104 nutrients, and organelles from the gametes.
105 In sexual reproduction, individual organisms are the donors of germ cells, but
106 only germ cells are involved in the biological processes of sexual reproduction, such
107 as meiosis and fertilization. Germ cells of unicellular organisms and some multicellular
108 organisms proceed the syngamy in the external environment. Some species with
109 sexual reproduction have special passages for sperms and eggs and special sites for
110 the development of fertilized eggs, and these organs, such as the penis, the vagina,
111 and the uterus, are often the criteria used to define the sexes of individuals.
112 Considering all species with sexual reproduction, however, the commonality of the birth
113 of new life is fertilization, not the combination of individuals or the specific reproductive
114 organs. That is, the unit of sexual reproduction is not the individual, but the germ cell.
115 Sex should thus describe the characteristics of the germ cells. Therefore, a definition
116 of sex that is suitable for all species with sexual reproduction must be based on cells,
117 not individuals. 118 Some people think that prokaryotes and viruses can reproduce sexually
119 because recombination of genetic materials in these organisms are found. However,
120 this raises the arguments about the definition of sexual reproduction in eukaryotes and
121 prokaryotes. Obviously, there is the concept of eukaryotic sexual reproduction first in
122 history, and the phenomenon of genetic recombination in eukaryotic sexual
123 reproduction is an important discovery in modern biology. Taking recombination as the
124 dentification standards for sexual reproduction is to use the nature of (eukaryotic)
125 sexual reproduction to in turn define (prokaryotic) sexual reproduction, which is a
126 problem of circular argument. Some of these arguments are described below. This
127 argument does not affect the present study because prokaryotes and viruses are
128 single-cells or single-particles, and the unit of their reproduction is also cells (or single
129 virus particles), resulting in the cellular characteristics of the speculative sex in these
130 species.
131
132 4 Cell-based sex in the hypotheses of the origin of sexual reproduction
133 The origin of sexual reproduction is hypothesized in the ancestral prokaryotes
134 or ancestral eukaryotes according to different evolutionary biologists, but each
135 hypothesis uses single cells as the starting point for sexual units.
136 Some biologists argue that sexual reproduction originated from prokaryotic
137 cells for maintaining and improving genetic materials. To overcome the genetic
138 damage, bacteria have the sexuality to transfer fragmented genome between cells,
139 with the related enzymes whose primary functions are DNA replication and repair
140 (Dougherty, 1955; Bernstein et al., 1984). Another opinion argues that, however, the
141 benefits of the transferred bacterial genomic fragments from donner cells to the
142 recipient cells are random, and the result of long-term natural selection to remove
143 deleterious transferred genes misled researchers to regard recombination as the
144 benefit of sexual reproduction, thus whether the bacteria have sexual reproduction or
145 not is questioned (Redfield, 2001). Moreover, some evidence shows that the external
146 nucleic acids caught by bacteria may be digested in the cells (Vos et al., 2019). Is the
147 phenomenon of release and uptake of DNA by bacteria likened to the process of 148 animals’ ejecting and receiving sperms? The answer may be no: in multicellular
149 animals with in vivo insemination, sperms, what male individuals ejaculate, are seed
150 cells of new lives and the partners of eggs, and what female individuals actually receive
151 are embryos; in multicellular animals with external fertilization, female individuals also
152 release eggs outside the bodies. In any case, it is the cells that exchange genetic
153 material in the hypotheses that sexual reproduction originated from prokaryotes.
154 The focuses on the origin of eukaryotic sexual reproduction are cytological
155 events, not physiological, metabolic, or behavioral features of multicellular individuals.
156 Meiosis is a key step of eukaryotic sexual reproduction. Cavalier-Smith (2010)
157 suggests that sexual reproduction originated before or at the same time as the
158 formation of eukaryotic cells; the origin of meiosis, a correcting process of the failure
159 of mitosis, is prior to or straddled the genesis of eukaryotic cells; cell fusion, whose
160 roles increase nutrients and genetic materials, is initially controlled by the earliest
161 eukaryotic cells. Most researches, however, support that the origin of eukaryotic cell is
162 prior to the meiosis. According to some evidences of molecular genetics and cell
163 biology, especially related to fungi, parasexual process is considered as the evolutional
164 prelude of meiosis, and mating-type is one of the effective ways to find mating partner
165 cells (Goodenough and Heitman, 2014). Some studies report that in the ancestral
166 eukaryotic cells, an insertion step of homolog synapsis into normal mitosis is the origin
167 of meiosis, whose initial function is to restrict, not promote, recombination (Wilkins and
168 Holliday, 2009); Gradually, obtaining more genetic diversities is a significant advantage
169 for sexual reproduction of cells, e.g., the syngamy of eggs and sperms, the former
170 conserving genetic stability for the perpetuation of the species and the latter pursuing
171 better genetic diversity via increasing the number of cell divisions (Xu, 2017).
172 Viruses, particles with genetic materials encased in protein shells, do not
173 have structures of normal cells. Some viruses, e.g., RNA viruses, are found to have
174 recombination of nucleic acids, either between inter-/intra-species viruses or between
175 viruses and host genomes (Worobey and Holmes, 1999). Thus, recombination is
176 regarded as the evidence of sexual reproduction in RNA viruses (Chao, 1988), even
177 the RNA-virus recombination is taken as one of the origin events of sexual production 178 (Bernstein et al., 1984). In this case, the unit of the sex, although not a normal cell, is
179 a single independent virus particle. However, the viewpoint that recombination of
180 genetic materials is the evidence of sexual reproduction in RNA viruses is questioned
181 (Simon-Loriere and Holmes, 2011), although a few hypotheses of advantages in sexual
182 reproduction are related to recombination (Kondrashov, 1993). If recombination is the
183 basis for identifying sexual reproduction, is the processes of transfection, transduction,
184 or gene editing technology also belong to sexual reproduction?
185 According to the origin of sexual reproduction, sexual reproduction in
186 eukaryotes is based on meiosis and syngamy, and the sex is the feature of syngamy;
187 Thus, the cell is the unit of sex. Taking a step back, even if recombination is the origin
188 of sexual reproduction, donors or recipients of genetic material involved in
189 recombination are also cells, including virus particles.
190
191 5 The definition of sex based on cells and reproduction
192 The definition of sex based on cells and reproduction is as follows: Sex
193 describes the type of material contributes to reproduction or to the formation of
194 totipotent cells from germ cells. In this definition, it is emphasized that sex is a
195 characteristic of germ cells. The significance of this definition of sex is limited to
196 reproduction. The melding of different sexes of cells forms zygotes, fertilized eggs,
197 totipotent stem cells, etc., which can develop into individuals. This definition focuses
198 on material contributions to reproduction.
199 Thus, the standard for distinguishing the sex of germ cells ought to rely on
200 their contributions to reproduction, specifically, their contributions to the development
201 of zygotes. The identification of females and males in oogamy is typical: female
202 gametes (eggs) provide zygotes with not only genetic materials but also nutrition,
203 organelles, etc., for the development of new individuals, while male gametes (sperms)
204 mainly provide genetic materials to zygotes (Figure 1). Because sexual reproduction
205 is advantageous, melding of female gametes and male gametes is common. However,
206 the combination of female gametes and female gametes is not impossible, in some
207 cases, this is called parthenogenesis (Kono et al., 2004; Revazova et al., 2007). 208 However, melded sperm cannot form zygotes with the potential to develop, due to the
209 lack of nutrition, organelles, etc., for the nascent zygote cells. The so-called male
210 parthenogenesis is actually the melding of sperm (or nuclei) with other cells (or
211 enucleated cells) that contain nutrition and organelles for the zygotes (Schwander and
212 Oldroyd, 2016; Li et al., 2018).
213
214 Figure 1. Contribution of components from the female and the male to the zygote.
215
216 Many studies have described the multiple “sex” of fungi (Kronstad and Staben,
217 1997; Ni et al., 2011). However, the “sexes” in fungi are mating types and describe only
218 mating compatibility, a different concept from the sex in the present study, which
219 focuses on material contributions to reproduction. According to their provision of
220 genetic materials, nutrition, organelles, etc., the gametes of fungi are therefore females.
221 These diverse mating types lead to more opportunities for hybridization, allowing fungi
222 to obtain the benefits of genetic diversity. Although the present definition of sex based
223 on reproductive cells can include bacteria and viruses, the concept of sexual
224 reproduction without meiosis remains flawed, as discussed above.
225
226 6 Individual sex via quantitative proportion
227 Given its wide use in current sex systems and social lifestyles, the definition
228 of sex based on individuals will be difficult to replace immediately. One possible way
229 to resolve any conflict is that the germ cell definition of sex can be made compatible
230 with the individual definition. According to the definition of sex based on germ cells, the
231 important standard for assessing the sex of an individual is the potential to produce
232 different fertile gametes, e.g. for humans, eggs or sperms. By relying on the production
233 of different germ cells, sex can be determined by quantitative proportion.
234 The new individual sex is defined as follows: in a population at time T, if the
235 total amount of sperms in the population is SP, the total amount of eggs in the
236 population is EP, the amount of sperms in an individual is SI, and the amount of eggs
237 in the individual is EI, then the contribution of this individual for the population sperm 238 pool (CS) is calculated as
239 CS = SI÷SP,
240 the contribution of this individual for the population egg pool (CE) is calculated as
241 CE = EI÷EP,
242 the percentage male for this individual (M) is
243 M = CS÷(CS+CE)×100%,
244 and the percentage female for this individual (F) is
245 F = CE÷(CS+CE)×100%.
246 An example explaining this definition is showed in Figure 2. This is an
247 ecological definition of sex because of its relationship with the population reproductive
248 capacity. In addition, sex may vary with individual age. This definition is compatible
249 with and includes the current definition of sex based on individuals: if a man cannot
250 produce eggs and produces only sperms, no matter the amount, then he is 100% male;
251 similarly, if a woman cannot produce sperms and produces only eggs, no matter the
252 amount, then she is 100% female.
253
254 Figure 2. An example of individual sex based on the production of different gametes
255 contributed to the population
256
257 7 The effects of germ cell sex definition on sex determination systems
258 The mechanisms of sex determination systems, which were previously used
259 to interpret the determination of individual sexes, are probably more suitably explained
260 under the definition of sex basing on cells. There are usually sex determination
261 systems in the species with anisogametes, and the formation of sexes are from
262 undifferentiated cells, e.g., pluripotent stem cells in mammals, to differentiated
263 gametes, determined in the levels of genome, transcriptome, proteome, and
264 metabolome.
265 The differentiation of germ cells is biologically linked to chromosomal and
266 environmental determinants. Chromosomal sex-determined systems, which mean
267 sexes with genomic differences, are ubiquitous in heterogametic eukaryotic organisms, 268 such as XX/XY system in mammals and flower plants, ZW/ZZ system in birds and
269 reptiles, XX/X0 system in insects and nematodes, and UV system in alga (Dellaporta
270 and Calderon-Urrea, 1993; Bachtrog et al., 2014). Environmental sex-determined
271 systems, in which different sexes have the same genome, could be considered as
272 transcriptomic, proteomic, metabolomic differences induced by external factors. With
273 the cell-based definition of sex, hermaphroditic species also have sex-determined
274 systems. Of course, the mechanisms of sex determination in hermaphrodites are non-
275 genomic differences, although some details remain unknown.
276 Sex determination, no matter using the cell-based definition of sex or the
277 individual definition of sex, can be described as a series of cytological events (Figure
278 3). For eukaryotes, including animals and plants, the sex determination process can
279 be described as a general mode: fully plastic cells with full set of chromosomes →
280 partially differentiated cells with full set of chromosomes (→ partially differentiated cell
281 with half set of chromosomes) → gametes. The molecular mechanism of this process
282 differs greatly from species to species in details. The roles of mammalian gametes’
283 determined biomolecules, such as SRY, SOX9, FGF9, and PDG2, have been studied
284 in depth, and the gametes reconstituted in vitro by pluripotent stem cells can be used
285 to form health offspring (Kashimada and Koopman, 2010; Hayashi et al., 2011; Hikabe
286 et al., 2016; Saitou and Miyauchi, 2016). The results in these experiments the
287 reconstituting gametes in vitro support the rationality of the definition of sex based on
288 reproductive cells.
289
290 Figure 3. General cytological event chains of sex determination in mammals
291
292 There are advantages in sexual reproduction, resulting in the fixation of this
293 process. From cytologically evolutionary perspective, sex chromosomes evolve later
294 than sex (Charlesworth and Charlesworth, 1978; Charlesworth, 1991; Furman et al.,
295 2020) and germ cell specification by inductive signals is more prevalent than that by
296 inherited determinants (Extavour and Akam, 2003), so sex determination systems may
297 not be the cause or basis of sex, but the result or assurance of sex. For an example, 298 to produce more well-nourished offspring, gametes that have enough materials to form
299 individuals are selected naturally, and sperms should be eliminated evolutionarily
300 because they mainly provide only genetic materials; but the diverse mutations resulted
301 from multiple divisions led zygotes to adapt to environmental changes, so assurances
302 for maintaining sperms are necessary, and sex determination system may be one of
303 the systems to protect sperms from being eliminated.
304
305 8 The effects of germ cell sex definition on sex differences
306 Sex differences are the differences between sexes. Once the definition of sex
307 is limited to germ cells, multicellular individuals previously defined as female, male,
308 hermaphroditic or trans-sex do not have sex. Similarly, the features of individuals in
309 multicellular organisms do not constitute sex differences but represent the directive
310 and eclectic mechanisms of sexual reproduction, and they have plastic characteristics.
311 Sex differences, which were sometimes regarded as sex identification criteria in
312 individual sex knowledge systems, must be reconsidered. Some traits previously
313 considered sex differences are involved in accomplishing fertilization.
314 Differences in gametes are the essential sex differences (Figure 4). Take
315 eggs and sperms for example. Organisms invest different resources in eggs and
316 sperms. Eggs are rich in nutrients and have intact organelles. Eggs are usually filled
317 with egg yolk resulting in large cells, and mature eggs in some species can be seen
318 with the naked eyes. In contrast, sperms are smaller and have few nutrients except
319 the nutrients and energy required for their short trip to find the eggs. In terms of quantity,
320 eggs are scarcer than sperms. Although a large number of precursor oocytes are
321 formed, fewer eggs are finally produced. For example, a woman has hundreds of
322 thousands of oocytes, but ovulates only a few hundred mature eggs in her lifetime. In
323 contrast, the number of sperm is astronomical, and the renewal speed of sperm is
324 rapid. A man may release trillions of sperm in his lifetime. In most cases, the sperm
325 and the egg undergo fertilization at a ratio of 1:1. The eggs ovulated and sperms
326 released without fertilization die. Therefore, the survival rate of egg is much higher than
327 that of sperm. In ecological terms, eggs are K-selected cells that have a small number 328 and high survival rate, but sperms are R-selected cells that have a large number and
329 low survival rate.
330
331 Figure 4. Differences between gamete pairs.
332
333 Gamete-producing organs, which are called sex glands in most animals,
334 produce specific gametes and are the major indexes to anatomically discriminate
335 between males and females in the current sex definition based on individuals. Under
336 the definition of sex based on cells used in the present study, this is a logical error and
337 no sense to assign sex to sex glands. However, differences in sex glands are closely
338 related to gamete differences compared to other indexes of sexual differences in the
339 definition of sex based on individuals. In most cases, one kind of sex gland can
340 produce only one kind of gamete. Thus, it is, to some extent, acceptable that sex gland
341 differences are considered as a derived indicator of sexual identity.
342 Some biological molecules have sexual biases, such as the presence of yolk
343 in eggs, while some biological molecules can induce sex. However, biological
344 molecules do not have sex by either individual sex definition or the cell sex definition.
345 In individual sex system, sex chromosomes are the major index used to determine sex,
346 but different sex chromosomes can be found in a single individual (Hotta and Benzer,
347 1972; Kagami et al., 1995; Erlebacher and Fisher, 2017). In the definition of sex based
348 on cells, whether a sex chromosome occurs in the gametes is an important issue. For
349 example, sperms have both X chromosomes and Y chromosomes, but eggs usually
350 have only X chromosomes. If eggs with the Y chromosome cannot be found, the Y
351 chromosome can be regarded as a marker of sperm and the sex chromosomes
352 constitute a sexual difference. Sex hormones come from sex glands, other organs in
353 the individual body, or the external environment. Under the normal physiological
354 conditions, sex hormones can induce individual organisms to produce germ cells.
355 Sperms and eggs are sensitive to endogenous hormones in abnormal conditions, and
356 hormones outside of individuals, such as environmental hormones, reliably disrupt the
357 formation of gametes (Sonnenschein and Soto, 1998; Rochester, 2013). In the present 358 definition of sex based on germ cells, the question of whether sex hormones have sex
359 differences is meaningless unless it is confirmed that one type of sex hormone is
360 specific to gametes of a certain sex.
361 Individual sex differences of other morphological features, other organs and
362 behaviours can be affected by each other and/or influenced by hormones. From the
363 perspective of sex based on cells, however, the differences noted above in individuals
364 are not sex differences, although some of these differences support the process of
365 sexual reproduction, which centres on eggs and sperms.
366
367 9 The effects of the germ cell sex definition on gender equality
368 Gender equality is the concept that human individuals, regardless of gender,
369 have equality of status, available resources, and authority, and the present definition
370 of sex based on cells disrupts this definition of equality by removing the significance of
371 gender. Nevertheless, this definition of sex brings gender equality closer to its essence.
372 Human society is composed of human individuals, and equality is based on individuals.
373 Gender inequality is the inequality of individuals, and gender inequality is the inequality
374 of individuals imposed because of the different genders. That is, gender equality is one
375 type of individual equality. Competition between in high mammals occurs due to the
376 different requirements of females and males: females mainly have social requirements,
377 such as social status and the control of living resources; males intentionally or
378 unintentionally require the continuance of their DNAs (Xu, 2017). I suggest that these
379 differences in requirements between females and males result from males’ lack of the
380 ability to conceive and identify their DNA in offspring, so they annex the available
381 resources and claim higher social status, thus requiring females to cooperate to obtain
382 descendants. Once individual gender inequality is related to reproduction, it becomes
383 a sexual characteristic under the definition of sex based on reproductive cells.
384
385 10 Conclusion
386 The essence of sex is the distinction between items joined in sexual
387 reproduction, and the minimum unit of reproduction is the gamete cell. This is an 388 important biological basis for the definition of sex based on cells. Such a definition is
389 an issue worthy of extensive discussion. On the one hand, the cell-based definition of
390 sex needs additional observation and experiments, especially with regard to whether
391 using cellular materials, such as nutrients and organelles, to classify different sexes of
392 gametes is correct. On the other hand, because individual sex has existed for a long
393 time, the alternative definition thereof will greatly influence the existing knowledge
394 systems and social systems related to sex. Regardless of whether the definition of sex
395 based on gamete cells is acceptable, challenging and supplementing the existing
396 definition of sex and its flaws is beneficial for related biological and medical studies.
397
398 Conflict of Interest
399 The authors declare that they have no conflict of interest. 400 References
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Female Male
Genetic Genetic Nutrients Organelles materials materials
Zygote
Figure 1. Contribution of components from the female and the male to the zygote.
Number Number of egg of sperm Individual/Population Sex
50% Female Population 5 10 (3 Individuals) 50% Male
Individual 1 4 0 100% Female
33% Female Individual 2 1 4 67% Male
Individual 3 0 6 100% Male
Figure 2. An example of individual sex based on the production of different gametes contributed to the population
Inner mass cells Stem cells in Stem cells in Spermatogonia Spermatozoa Fertilized eggs in blastocyst genital ridges gonads or follicles or oocytes
Unipotent stem Differentiated Totipotent stem cells Pluripotent stem cells cells cells
Diploid Haploid
Sex determination with the sex definition based on individuals
Sex determination with the sex definition based on reproductive cells
Figure 3. General cytological event chains of sex determination in mammals
×
Extension of differences gamete pairs between Extension differences of Female Female
×
Female Female
×
Female Male
Figure 4. Differences between gamete pairs.