Influence of prenatal alcohol exposure on the process of neurobehavioral sexual differentiation

Alcohol Health & Research World, Spring, 1991 by Robert F. McGivern, Susan Barron

Males and females have distinct patterns of behavior and emotional expression, but what is the basis for these patterns? Sexual differentiation in the fetus is dependent on the hormone milieu, and alcohol affects the production and release of hormones. Thus, the development of gender-related differences also is affected by prenatal exposure to alcohol.

Gender-related behaviors constitute a significant category of social behavior. Although people are aware of differences between men and women in behaviors and emotional expression, the underlying biological mechanisms involved in these differences are not as well known. As a class, gender-related behaviors are referred to as sexually dimorphic, or sexually differentiated, behaviors. The range of gender-related behaviors extends far beyond the behaviors associated directly with reproduction to include gender- related differences in cognition and emotional response. This article briefly reviews the physiology of sexual differentiation and then considers how alcohol interacts with the mechanisms of differentiation.

Overview

Sexually dimorphic behaviors exist across a variety of mammalian species. In adult humans and animals, the expression of sexually dimorphic behaviors is influenced by both genetically determined processes and environmental events that occur throughout development, including early fetal development. Increasing evidence derived primarily from animals studies suggests that prenatal(1) exposure to alcohol is one environmental factor that can disrupt the development of several physiological and behavioral differences that occur during the process of sexual differentiation. The long-term effects of exposure to alcohol include compromised gonadal function, changes in gender- related brain areas, and alterations in sexually dimorphic behaviors.

The study of mammalian sex differences has exploded in the past 15 years, and with these studies has come an enhanced appreciation for the pervasive nature of the biological changes that occur during sexual differentiation. Sexual differentiation in humans, as in most mammals, is discerned most easily on the basis of observable physical differences. However, in addition to the observable anatomical differences, marked gender-related anatomical differences in the central nervous system (CNS) have been demonstrated in a number of recent studies. Such differences have been found in several areas of the brain, including the hypothalamus and the corpus callosum, and the spinal cord.

Gender-related differences in brain anatomy occur in a number of mammalian species, including rodents and humans (Arnold and Gorski 1984). These anatomical differences result from a differential exposure between males and females to sex steriods early in development. They are presumed to underlie the gender differences observed not only in copulatory behaviors but also in nonreproductive behaviors such as aggression, play behavior, maternal behavior, and spatial skills in animals (Beatty 1979, 1984), as well as gender differences in humans with respect to play behavior, mathematical reasoning, verbal skills, and spatial abilities (Beatty 1984; Benbow 1988; Gouchie and Kimura 1991; Kimura 1983). The result is a normal dimorphism between the sexes that is evident in brain, body, and behavior.

Sexual Differentiation

Normal sexual differentiation is determined by several factors--genetic, hormonal, and environmental--acting at different stages of development (see Table 1). Genetically determined sex, or one's genotype, is determined at conception. The subsequent activity of the sex chromosomes causes the indifferent embryonic gonad to differentiate into a testis or an ovary. Phenotypically determined sex, one's phenotype, is the physical manifestation of genotypic sex. It includes sex organ development and gender differences in brain organization and is directly under the control of hormones secreted by the gonads. Finally, gender identity, an individual's emotional identification with and acquisition of appropriate sex-related roles, results from an interaction between the environment and the actions of gonadal steriod hormones. It should be noted that for higher species, environmental factors appear to play a larger role in the expression of gender identification than they do for lower species.

During mammalian development, gonadal hormones "organize" the brain so that an individual will respond to later hormonal stimulation with a masculine or feminine behavior pattern. Hormonal organization occurs in both brain and periphery, and the effects of hormones are long lasting. Hormones act by influencing gene activity in the developing organism. For example, if rats (male or female) are exposed prenatally to adequate levels of testosterone at the proper point in fetal development and then are castrated as adults, they will respond to an injection of testosterone with masculine behavior patterns when in the presence of a receptive female. However, an adult male rat that was not exposed to adequate amounts of testosterone prenatally will fail to respond to a testosterone injection with normal levels of sexual behavior.