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Impact of sex and gonadal steroids on neonatal brain structure.

ABSTRACT: There are numerous reports of sexual dimorphism in brain structure in children and adults, but data on sex differences in infancy are extremely limited. Our primary goal was to identify sex differences in neonatal brain structure. Our secondary goal was to explore whether brain structure was related to androgen exposure or sensitivity. Two hundred and ninety-three neonates (149 males) received high-resolution structural magnetic resonance imaging scans. Sensitivity to androgen was measured using the number of cytosine, adenine, guanine (CAG) triplets in the androgen receptor gene and the ratio of the second to fourth digit, provided a proxy measure of prenatal androgen exposure. There was a significant sex difference in intracranial volume of 5.87%, which was not related to CAG triplets or digit ratios. Tensor-based morphometry identified extensive areas of local sexual dimorphism. Males had larger volumes in medial temporal cortex and rolandic operculum, and females had larger volumes in dorsolateral prefrontal, motor, and visual cortices. Androgen exposure and sensitivity had minor sex-specific effects on local gray matter volume, but did not appear to be the primary determinant of sexual dimorphism at this age. Comparing our study with the existing literature suggests that sex differences in cortical structure vary in a complex and highly dynamic way across the human lifespan.

SUBMITTER: Knickmeyer RC

PROVIDER: S-EPMC4153808 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Impact of sex and gonadal steroids on neonatal brain structure.

Knickmeyer Rebecca C RC Wang Jiaping J Zhu Hongtu H Geng Xiujuan X Woolson Sandra S Hamer Robert M RM Konneker Thomas T Styner Martin M Gilmore John H JH

Cerebral cortex (New York, N.Y. : 1991) 20130519 10

There are numerous reports of sexual dimorphism in brain structure in children and adults, but data on sex differences in infancy are extremely limited. Our primary goal was to identify sex differences in neonatal brain structure. Our secondary goal was to explore whether brain structure was related to androgen exposure or sensitivity. Two hundred and ninety-three neonates (149 males) received high-resolution structural magnetic resonance imaging scans. Sensitivity to androgen was measured using ...[more]

PMID: 23689636

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Project description:To examine the hormonal and immunological mechanisms that mediate sex differences in susceptibility to malaria infection, intact and gonadectomized (gdx) C57BL/6 mice were inoculated with Plasmodium chabaudi AS-infected erythrocytes, and the responses to infection were monitored. In addition to reduced mortality, intact females recovered from infection-induced weigh loss and anemia faster than intact males. Expression microarrays and real-time reverse transcription-PCR revealed that gonadally intact females exhibited higher expression of interleukin-10 (IL-10), IL-15Ralpha, IL-12Rbeta, Gadd45gamma, gamma interferon (IFN-gamma), CCL3, CXCL10, CCR5, and several IFN-inducible genes in white blood cells and produced more IFN-gamma than did intact males and gdx females, with these differences being most pronounced during peak parasitemia. Intact females also had higher anti-P. chabaudi immunoglobulin G (IgG) and IgG1 responses than either intact males or gdx females. To further examine the effector mechanisms mediating sex differences in response to P. chabaudi infection, responses to infection were compared among male and female wild-type (WT), T-cell-deficient (TCRbetadelta-/-), B-cell-deficient (microMT), combined T- and B-cell-deficient (RAG1), and IFN-gamma knockout (IFN-gamma-/-) mice. Males were 3.5 times more likely to die from malaria infection than females, with these differences being most pronounced among TCRbetadelta-/-, microMT, and RAG1 mice. Male mice also exhibited more severe weight loss, anemia, and hypothermia, and higher peak parasitemia than females during infection, with WT, RAG1, TCRbetadelta-/-, and microMT mice exhibiting the most pronounced sexual dimorphism. The absence of IFN-gamma reduced the sex difference in mortality and was more detrimental to females than males. These data suggest that differential transcription and translation of IFN-gamma, that is influenced by estrogens, may mediate sex differences in response to malaria.

Project description:BackgroundGonadal steroid hormones have been suggested as the underlying mechanism responsible for the sexual dimorphism observed in metabolic diseases. Animal studies have also evidenced a causal role of the gut microbiome and metabolic health. However, the role of sexual dimorphism in the gut microbiota and the potential role of the microbiome in influencing sex steroid hormones and shaping sexually dimorphic susceptibility to disease have been largely overlooked. Although there is some evidence of sex-specific differences in the gut microbiota diversity, composition, and functionality, the results are inconsistent. Importantly, most of these studies have not taken into account the gonadal steroid status. Therefore, we investigated the gut microbiome composition and functionality in relation to sex, menopausal status, and circulating sex steroids.ResultsNo significant differences were found in alpha diversity indices among pre- and post-menopausal women and men, but beta diversity differed among groups. The gut microbiota from post-menopausal women was more similar to men than to pre-menopausal women. Metagenome functional analyses revealed no significant differences between post-menopausal women and men. Gonadal steroids were specifically associated with these differences. Hence, the gut microbiota of pre-menopausal women was more enriched in genes from the steroid biosynthesis and degradation pathways, with the former having the strongest fold change among all associated pathways. Microbial steroid pathways also had significant associations with the plasma levels of testosterone and progesterone. In addition, a specific microbiome signature was able to predict the circulating testosterone levels at baseline and after 1-year follow-up. In addition, this microbiome signature could be transmitted from humans to antibiotic-induced microbiome-depleted male mice, being able to predict donor's testosterone levels 4 weeks later, implying that the microbiota profile of the recipient mouse was influenced by the donor's gender. Finally, obesity eliminated most of the differences observed among non-obese pre-menopausal women, post-menopausal women, and men in the gut microbiota composition (Bray-Curtis and weighted unifrac beta diversity), functionality, and the gonadal steroid status.ConclusionsThe present findings evidence clear differences in the gut microbial composition and functionality between men and women, which is eliminated by both menopausal and obesity status. We also reveal a tight link between the gut microbiota composition and the circulating levels of gonadal steroids, particularly testosterone. Video Abstract.

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Impact of sex and gonadal steroids on neonatal brain structure.

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Impact of sex and gonadal steroids on neonatal brain structure.

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