A Yin-Yang Effect between Sex Chromosome Complement and Sex Hormones on the Immune Response

Palaszynski, Karen M.; Smith, Deborah L.; Kamrava, Shana; Burgoyne, Paul S.; Arnold, Arthur P.; Voskuhl, Rhonda R.

doi:10.1210/en.2005-0284

Cited by 128 publications

(107 citation statements)

References 27 publications

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“…Moreover, T concentrations in plasma of gonad-intact mice were sexually dimorphic (females have lower testosterone levels than males) but not different in the two groups of females, or between the two groups of males. This pattern (no XX versus XY Ϫ difference, but a sex difference), with respect to T concentrations, has also been reported in this cross on another inbred (SJL) background (Palaszynski et al, 2005). Ovary intact XX and XY Ϫ females undoubtedly have differences in hormone levels because XY Ϫ females have severe oocyte depletion resulting in subfertility or sterility (Mahadevaiah et al, 1993).…”

Section: Discussionsupporting

confidence: 78%

“…Ovary intact XX and XY Ϫ females undoubtedly have differences in hormone levels because XY Ϫ females have severe oocyte depletion resulting in subfertility or sterility (Mahadevaiah et al, 1993). Although we have not controlled for any differences between XX and XY mice of the same gonadal sex in levels of gonadal hormones before gonadectomy, they do not differ on numerous other measures of sexual characters that would be influenced by global differences in gonadal hormones during development (De Vries et al, 2002;Markham et al, 2003;Wagner et al, 2004;Palaszynski et al, 2005).…”

Section: Discussionmentioning

confidence: 95%

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Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Gatewood¹,

Wills²,

Shetty³

et al. 2006

J. Neurosci.

219

227

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Across human cultures and mammalian species, sex differences can be found in the expression of aggression and parental nurturing behaviors: males are typically more aggressive and less parental than females. These sex differences are primarily attributed to steroid hormone differences during development and/or adulthood, especially the higher levels of androgens experienced by males, which are caused ultimately by the presence of the testis-determining gene Sry on the Y chromosome. The potential for sex differences arising from the different complements of sex-linked genes in male and female cells has received little research attention. To directly test the hypothesis that social behaviors are influenced by differences in sex chromosome complement other than Sry, we used a transgenic mouse model in which gonadal sex and sex chromosome complement are uncoupled. We find that latency to exhibit aggression and one form of parental behavior, pup retrieval, can be influenced by both gonadal sex and sex chromosome complement. For both behaviors, females but not males with XX sex chromosomes differ from XY. We also measured vasopressin immunoreactivity in the lateral septum, which was higher in gonadal males than females, but also differed according to sex chromosome complement. These results imply that a gene(s) on the sex chromosomes (other than Sry) affects sex differences in brain and behavior. Identifying the specific X and/or Y genes involved will increase our understanding of normal and abnormal aggression and parental behavior, including behavioral abnormalities associated with mental illness.

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Section: Discussionsupporting

confidence: 78%

Section: Discussionmentioning

confidence: 95%

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Gatewood¹,

Wills²,

Shetty³

et al. 2006

J. Neurosci.

219

227

View full text Add to dashboard Cite

show abstract

“…In addition, the effects of sex-linked genes and sex hormones may cancel each other out to yield similar physiology between the sexes. For instance, immune responses and cytokine production induced by autoantigens are enhanced in mice with an XY complement compared with mice with an XX complement, but such immune reactions are repressed by male sex hormones (Palaszynski et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

Sex-Specific Differences in Expression of Histone DemethylasesUtxandUtyin Mouse Brain and Neurons

Xu¹,

Deng²,

et al. 2008

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Although X inactivation is thought to balance gene expression between the sexes, some genes escape inactivation, potentially contributing to differences between males and females. Utx (ubiquitously transcribed tetratricopeptide repeat gene on X chromosome) is an escapee gene that encodes a demethylase specific for lysine 27 of histone H3, a mark of repressed chromatin. We found Utx to be expressed higher in females than in males in developing and adult brains and in adult liver. XX mice had a higher level of Utx than XY mice, regardless of whether they had testes or ovaries, indicating that the sexually dimorphic gene expression was a consequence of the sex chromosome complement. Females had significantly higher levels of Utx than males in most brain regions except in the amygdala. The regional expression of the Y-linked paralogue Uty (ubiquitously transcribed tetratricopeptide repeat gene on Y chromosome) was somewhat distinct from that of Utx, specifically in the paraventricular nucleus of the hypothalamus (high Uty) and the amygdala (high Utx), implying that the two paralogues may be differentially regulated. Higher expression of Utx compared with Uty was detected in P19 pluripotent embryonic carcinoma cells as well as in P19-derived neurons. This transcriptional divergence between the two paralogues was associated with high levels of histone H3 lysine 4 dimethylation at the Utx promoter and of histone H4 lysine 16 acetylation throughout the gene body, which suggests that epigenetic mechanisms control differential expression of paralogous genes.

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“…If XX and XY males, for example, differ in their response to pain, then one can conclude that Y chromosome genes present only in the XY mice, or X chromosome genes (present in different genomic doses in XX vs. XY, and with different parental genomic imprints), cause the difference [12,49,69,153]. The sex chromosome effect does not tell where the X or Y chromosome genes act to cause the sex difference, although direct actions of Y chromosome genes have been demonstrated in the brain [52].…”

Section: Future Directionsmentioning

confidence: 99%

“…In the absence of previous evidence for large menstrual/estrous cycle-related variations in the measure of interest, it is not absolutely necessary to test females in specific stages. However, a failure to observe sex differences in pain can be interpreted in multiple ways: (1) no sex difference exists; (2) the observed sex difference occurs only when females are in a particular stage of the menstrual or estrous cycle (e.g., [193]), and the sex difference could not be discerned due to "averaging" across the cycle; (3) a sex difference in mechanism exists even though the magnitude of the phenomenon under study is similar in males and females (e.g., [126,127]); or (4) two sex-specific mechanisms exist that cancel each other out, resulting in no phenotypic sex difference [50,153]. Thus, in the case of a negative finding when comparing gonadally intact females vs. males, interpretations 2, 3, and 4 should be acknowledged.…”

mentioning

confidence: 99%

Studying sex and gender differences in pain and analgesia: A consensus report

Greenspan

Craft

LeResche

et al. 2007

Pain

846

633

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In September 2006, members of the Sex, Gender and Pain Special Interest Group of the International Association for the Study of Pain met to discuss the following: (1) what is known about sex and gender differences in pain and analgesia; (2) what are the "best practice" guidelines for pain research with respect to sex and gender; and (3) what are the crucial questions to address in the near future? The resulting consensus presented herein includes input from basic science, clinical and psychosocial pain researchers, as well as from recognized experts in sexual differentiation and reproductive endocrinology. We intend this document to serve as a utilitarian and thought-provoking guide for future research on sex and gender differences in pain and analgesia, both for those currently working in this field as well as those still wondering, "Do I really need to study females?" Keywords Sex differences; Gonadal hormones; Estrogens The case for studying sex and gender differences in pain and analgesiaThe pain field has moved from debating whether sex differences in pain exist to recognizing the importance of these differences. Attention is now directed toward understanding (1) what conditions lead to the expression of sex and gender differences in pain experience and reactivity, (2) what mechanisms underlie these differences, and (3) how these differences can inform clinical management of pain.As noted in a recent review, at least 79% of animal studies published in Pain over the preceding 10 years included male subjects only, with a mere 8% of studies on females only, and another 4% explicitly designed to test for sex differences (the rest did not specify) [142]. Given the substantially greater prevalence of many clinical pain conditions in women vs. men [20,199], and growing evidence for sex differences in sensitivity to experimental pain and to analgesics [21,41,213], we recommend that all pain researchers consider testing their hypotheses in both sexes, or if restricted by practical considerations, only in females. It is invalid to assume that data obtained in male subjects will generalize to females, and the best non-human model of the modal human pain sufferer -a woman -is a female animal. If only males are examined in a given study, it is important that a rationale for exclusion of females be provided and that the potential limitation in generalizability of the findings be addressed in the discussion, particularly when examining a pain phenomenon that occurs with greater prevalence or severity in females. In both preclinical and clinical studies, a comparison of both sexes will further our understanding of individual differences in sensitivity to pain and analgesia, thus improving our ability to treat and prevent pain in all people. General considerationsTwo issues of terminology are important. First, the term "sex" refers to biologically based differences, while the term "gender" refers to socially based phenomena. Although biological sex exerts a major influence on one's gender identity, sex and gender a...

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A Yin-Yang Effect between Sex Chromosome Complement and Sex Hormones on the Immune Response

Cited by 128 publications

References 27 publications

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Sex Chromosome Complement and Gonadal Sex Influence Aggressive and Parental Behaviors in Mice

Sex-Specific Differences in Expression of Histone DemethylasesUtxandUtyin Mouse Brain and Neurons

Studying sex and gender differences in pain and analgesia: A consensus report

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