An Introduction to Sex Differences in Development – What are ‘sex differences’ as a whole?
Sex differences can be defined as ‘traits that are sexually dimorphic between males and females’. Us humans (Homo sapiens) consist of 46 chromosomes, with two chromosomes playing a vital role in sex development: the X and Y chromosomes. These are sex chromosomes, where the presence or absence of a Y chromosome in the genome of a human can determine their sex.
Figure 1: the 23rd chromosome pair of a female and a male
Females consist of an XX pair in their genome, with one X chromosome inherited from their father and mother. Whereas males consist of an XY pair in the genome, with the X chromosome inherited from the mother and the Y chromosome inherited from the father. The Y chromosome then plays a role in sexual development which then results in the sex differences between males and females. This will be explained later on in this wiki.
Back to the idea of sex differences as a whole, differences in physical, psychological, cognitive and behavioural characteristics are considered [1] (Szadvari et al., 2023). Some examples include features involved with reproductive roles, hormonal systems and even their immune system. This wiki will discuss the origins of sex differences and it’s development – while exploring the genetic factors that play a role in sex differences.
The Evolution of Sex Differences:
The concept of how sex differences has originated is a widely debated topic. Charles Darwin proposed a mechanism as to how it originated in his book: The Descent of Man. He describes his theory of sexual selection. The sexual selection theory involves the idea that the evolution of traits are determined by reproductive success – as to what traits are desired for reproduction within a population [2] (Morrow, 2015). Therefore, males would have to exhibit traits that were more desired such as a stronger body shape. This is best visualized through the Bateman gradient – which describes how female reproductive success is limited by resource availability and how male reproductive success is limited by access to mates. The evolution of sex differences can then be seen as driven by differences in life history strategies that enable males and females to maximize reproductive success over a lifetime [3] (Choleris et al., 2018).
Figure 2: the Bateman gradient to visualise reproductive success within the male and female populations
Then investigators in this field would focus on the main sex differences such as the gonads, external and internal genitalia as well as behaviour. Only by the 20th century, they started investigating how the sex chromosomes and gonadal secretions cause sex differences.
With a trait to become sexually dimorphic, selection acting on it needs to become sex-specific [2] (Morrow, 2015). The trait then enters the second stage where the constraints of the genetic architecture of the trait may prevent it from becoming sexually dimorphic – if this constraint is lifted, then the third stage occurs where a limited degree of sexual dimorphism occurs. The trait ends up being sex-specific and the final stage occurs where the trait acts in a stabilizing manner for both sexes – however, this evolutionary model is univariate, which takes a single trait and predicts its evolutionary path based on how selection acts upon it and its genetic constraints. However, traits act in a matrix of quantitative traits, so considering this evolutionary model can come with drawbacks.
Therefore, with the evolution of sex differences, we can determine that the sex chromosomes would’ve undergone sexual selection and went past their genetic constraints – and this would’ve led to the development of the gonadal hormones, differing in the two sexes. Thanks to these evolutionary events, there are now the sex differences present in males and females now.
Why does studying the evolutionary causes of sex differences in traits matter? The evolutionary causes of sex differences can then aid our understanding of sex differences in disease – and even aid in sex-targeted therapies in medicine.
What Are The Main Sex Differences between Males and Females? (The Developmental Pathways and Structures involved)
As mentioned before, the presence and absence of the Y chromosome plays a big factor in determining the sex differences between males and females. This is mainly shown through the male-specific effects of the Y chromosome – such as the expression of the Sry gene [4] (Arnold, 2017). The Sry gene causes the differentiation of the testes and sets up lifelong sex differences in terms of gonadal hormones. The absence of the Sry gene results in ovarian development – therefore the presence or absence of the gene leads to the sexual differentiation of the gonads. The differentiation of gonads between males and females leads to life-long sex differences – where there are differing levels of testosterone, estradiol and progesterone within males and females. These hormonal factors have even been shown to cause the majority of sex differences in the brain.
The sex differences of brain development within the two sexes is a widely researched topic. Brain development diverges in males and females in response to androgen production by the testis – which we have established is dependent on the Sry gene. It was found that brain sex differences begin in the womb – and are established during the critical periods. Critical periods are defined as ‘developmental windows’ where a physiological (or anatomical) structure in the brain is established [5] (McCarthy, 2016). These are subject to external or internal stimuli, such as hormones. The Sry gene codes for a transcription factor called TDF (testis-determining factor), and we know that it results in the gonad differentiating into a testis. This results in the brain structure changing to support the gonad, therefore sex differences result where a male brain structure would support pulsatile secretion of the luteinizing hormone to produce testosterone and the female brain structure to generate surges of the luteinizing hormone to correspond with ovulation.
Future directions:
There are several aspects to consider for future research. One aspect is the analysing the influence of hormones on disease related to the sex differences. We know how the gonadal hormones result in sex differences but there is still much to learn about how the gonadal hormones (like estrogen and testosterone) influence health and disease. For example, researchers are exploring how these hormones might contribute to the development of autoimmune diseases, mental health conditions, and cardiovascular diseases. More research on this can then lead to sex-related therapies. Another aspect is analysing neuroscience in a sex difference context as there’s a lot of interest in understanding how sex differences might influence the development and functioning of the brain, which in turn could affect the risk of neurological and psychiatric disorders. This includes conditions like depression, anxiety, autism spectrum disorder, and Alzheimer’s disease. We have discussed how sex differences on the brain would occur, therefore it has been established.
Researchers are also becoming more interested in intersectionality – the study of how different aspects of a person’s identity (like their sex, race, and socioeconomic status) can interact to affect health. For example, a woman of a certain ethnic group might have a different risk profile for a particular disease compared to a woman of another ethnic group or a man of the same ethnic group. So investigating the sex differences involved, in conjunction with social factors could really aid in sex-specific therapies within populations.
References:
[1] Ivan, S., Daniela, O., & Jaroslava, B. D. Sex differences matter: Males and females are equal but not the same. Physiology & Behavior (2023). https://www.sciencedirect.com/science/article/pii/S0031938422003420
[2] Morrow, E. H. The evolution of sex differences in disease. Biology of sex differences (2015). https://link.springer.com/article/10.1186/s13293-015-0023-0
[3] Choleris, E., Galea, L. A., Sohrabji, F., & Frick, K. M. Sex differences in the brain: Implications for behavioral and biomedical research. Neuroscience & Biobehavioral (2018). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751942/
[4] Arnold, A. P. A general theory of sexual differentiation. Journal of neuroscience research (2017). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5369239/
[5] McCarthy, M. M. Sex differences in the developing brain as a source of inherent risk. Dialogues in clinical neuroscience (2022). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5286722/