Disruptions in reproductive health, sex hormonal profiles, and hypothalamic hormone receptors content in females of the C58/J mouse model of autism.

Autism Spectrum Disorder (ASD) is characterized by differences in social communication and interaction, as well as areas of focused interests and/or repetitive behaviors. Recent studies have highlighted a higher prevalence of endocrine and reproductive disturbances among females on the autism spectrum, hinting at potential disruptions within the hypothalamus-pituitary-ovary (HPO) axis. This research aims to explore the reproductive health disparities in ASD using an animal model of autism, the C58/J inbred mouse strain, with a focus on reproductive performance and hormonal profiles compared to the C57BL/6J control strain. Our findings revealed that the estrous cycle in C58/J females is disrupted, as evidenced by a lower frequency of complete cycles and a lack of cyclical release of estradiol and progesterone compared to control mice. C58/J females also exhibited poor performance in several reproductive parameters, including reproductive lifespan and fertility index. Furthermore, estrogen receptor alpha content showed a marked decrease in the hypothalamus of C58/J mice. These alterations in the estrous cycle, hormonal imbalances, and reduced reproductive function imply dysregulation in the HPO axis. Additionally, our in-silico study identified a group of genes involved in infertility carrying single-nucleotide polymorphisms (SNPs) in the C58/J strain, which also have human orthologs associated with autism. These findings could offer valuable insights into the molecular underpinnings of neuroendocrine axis disruption and reproductive issues observed in ASD.

Hormonal correlates of energetic condition in mantled howler monkeys.

Hormones have a key role in energy allocation, so their study allows understanding individual metabolic strategies. Because different hormones convey different information on the responses of individuals to energetic demands, a simultaneous analysis of variation in multiple hormones may offer a more reliable picture of metabolic strategies than single hormone assessments. In this study we focused on determining which factors were related to variation in fecal glucocorticoid and thyroid hormone metabolites in wild mantled howler monkeys (Alouatta palliata). Over 12months, we determined fecal glucocorticoid and thyroid hormone metabolite levels of 11 adults belonging to two groups, and examined the relationship between hormone metabolites and a variety of behavioral, physiological, and ecological factors (e.g., food intake, sex/reproductive state, activity, participation in agonistic interactions). We found that glucocorticoids were elevated in gestating and lactating females compared to males and cycling females, and were also higher when individuals were more active and participated in agonistic interactions. Thyroid hormone levels were also related to sex/reproductive state and activity, but were additionally positively related to fruit intake and negatively related to young leaf intake. Our study demonstrates that the non-invasive measurement of glucocorticoid and thyroid hormones of howler monkeys allows assessing different underlying physiological processes. By combining different biomarkers, which has seldom been done with wildlife, we could also parse the influence of psychological vs. metabolic challenges for individual energetic condition, which may be instrumental for deciding which factors should be accounted for when studying different hormone-behavior interactions.

Association between high serum estradiol levels and delirium among hospitalized elderly women.

BACKGROUND: Delirium is a common and serious disorder among hospitalized elderly individuals. We investigated the association between serum estradiol levels and incident delirium. METHODS: Longitudinal study of 141 women ≥ 70 years old admitted to a tertiary care hospital in Mexico City. All participants underwent a comprehensive geriatric assessment. Blood samples for cortisol and estradiol determination were obtained at hospital admission. Incident delirium was investigated until participants were discharged. Multivariate models were run to test the independent association between estradiol levels and incident delirium. RESULTS: Twenty-three (16.3%) participants developed delirium. Estradiol levels were higher among women with incident delirium compared with non-affected women. Multivariate logistic regression analysis showed that serum estradiol levels were associated with incident delirium even after adjusting for multiple confounding covariates, including cortisol levels (OR: 1.93; 95% CI: 1.28-2.92). CONCLUSIONS: Elderly women with high serum estradiol levels at hospital admission had an increased risk for incident delirium. Serum estradiol may be a biomarker for increased risk of delirium.

Effects of neurointermediate pituitary lobectomy and desmopressin on acute experimental autoimmune encephalomyelitis in Lewis rats.

OBJECTIVE: The role of arginine vasopressin (AVP) as a direct immune regulator has not yet been clarified, and more work is needed to assess its involvement in the immunoneuroendocrine network. In the present study, the effects of neurointermediate pituitary lobectomy (NIL) and desmopressin (DP), an agonist of AVP, on acute experimental autoimmune encephalomyelitis (EAE) in female Lewis rats were evaluated. The activity of the hypothalamic-pituitary-adrenocortical (HPA) axis was also assessed. METHODS: Five groups of rats were used, as follows: (1) sham-operated (SHAM) rats, (2) SHAM + DP rats, (3) NIL rats, (4) NIL + DP rats and (5) untreated normal control rats. DP treatment started 2 weeks after surgery, and immunization to induce EAE was carried out 1 week later. RESULTS: SHAM rats developed full-blown clinical and histological signs of EAE and activation of the HPA axis. SHAM + DP animals had mild clinical signs of EAE, inflammatory infiltrations in the spinal cord and an activated HPA axis. NIL animals developed minimal EAE, scanty spinal cord inflammation and no changes in HPA axis activity. NIL + DP rats developed severe clinical signs of EAE, extensive spinal cord inflammatory infiltrations and marked activation of the HPA axis. CONCLUSIONS: NIL decreased the cell-mediated immune response, while DP in NIL animals restored the immune response. AVP is directly involved in the maintenance of immune competence.

Seasonality of LH, testosterone and sperm parameters in spider monkey males (Ateles geoffroyi).

There are no reported data on hormonal fluctuations in black-handed spider monkey males. On previous research about the reproductive physiology of this monkey we have found that during the dry season females show ovulatory estrogen peaks and males present the best quality semen. As part of an ongoing research, in this study we assessed seasonal variations in the concentration of serum luteinizing hormone (LH) and testosterone (T) in three adult spider monkey males to corroborate the seasonal reproductive synchrony. At the same time sperm count and motility were evaluated to search for any correlation between those sperm parameters and hormonal concentrations. We took blood and semen samples (by electroejaculation) of anesthetized males throughout the rainy (June-September) and dry (October-May) months. Our results revealed that T and LH were higher throughout the dry season and there was a significant correlation between T concentration and sperm count. Although higher during the dry season, sperm motility tended to correlate with testosterone and LH levels. These results demonstrated that black-handed spider monkeys have a tendency to show a seasonal pattern of reproduction being the dry season the most likely time to achieve fertilization.

Negative correlation between testosterone and TNF-α in umbilical cord serum favors a weakened immune milieu in the human male fetoplacental unit.

Clinical and epidemiological evidence supports that pregnancies carrying a male fetus are more vulnerable to infections and preterm birth, probably due to testosterone immunosuppressive properties. In human placentas, testosterone lowers the expression of CYP27B1, the vitamin D (VD)-activating enzyme, diminishing cathelicidin synthesis, a potent VD-dependent antimicrobial peptide (AMP). VD also stimulates other AMPs, including defensins. To get insights into the increased male vulnerability mechanisms, we investigated the relationship between fetal sex and the immunoendocrine milieu at the fetoplacental unit. For this, umbilical vein serum and placental samples were collected from healthy newborns. In males' serum, testosterone levels were significantly higher and negatively associated with TNF-α, a cytokine that strengthens the immune response. Males showed lower serum TNF-α and increased levels and gene expression of the immunosuppressive cytokine IL-10. Only in female samples there was a positive association (P < 0.05) between AMPs and both TNF-α and CYP27B1 and between 25-hydroxyvitamin D3 and IL-1ß serum levels. Accordingly, VD-metabolites (25-hydroxyvitamin D3, calcitriol) significantly stimulated IL-1ß gene expression in cultured trophoblasts. Interestingly, IL-1ß mRNA correlated positively with defensins (P < 0.05) in males, but not with cathelicidin expression, which was significantly diminished in comparison to females. Our data suggest that high umbilical serum testosterone and IL-10 in males could explain reduced TNF-α levels and lack of association between VD-dependent innate immunity markers and proinflammatory cytokines expression in the fetoplacental unit. Altogether, our observations imply a restricted basal immune milieu in males compared to females, which may help understand the higher male susceptibility to adverse perinatal outcomes.

Testosterone, the progesterone/estradiol ratio, and female ratings of masculine facial fluctuating asymmetry for a long-term relationship.

Idiosyncratic variation within the normal range of androgens levels in women account for significant variations in personality and behavior. We studied if testosterone introduces significant biases in women's perception of fluctuating symmetry of male faces suitability for a long-term relationship. Participants were 145 female college students asked to rate in a two-choice forced paradigm the attractiveness, suitability as a long-term partner, and economic success, fatherliness and fidelity of an asymmetric and a symmetric male face. Since our sample consists of random women interested in participating, whether for personal reasons or because they were paid to participate, we controlled for menstrual phase. All participants provided salivary samples to determine testosterone (T), estradiol (E2) and progesterone (P4) levels. When the P4/E2 was low and T low-to-normal, the symmetric face was rated as more attractive, and a desirable long-term partner, but these preferences changed to the opposite when P4/E2 was high. In high T women, neither face was rated as more attractive, independently from the P4/E2 ratio, but the asymmetric face was preferred as a long-term partner when conception risk was high, changing to prefer the symmetric face as the P4/E2 increased. The overall perception of male faces was that the symmetric face was more economical successful but a poor parent and highly unfaithful compared to the asymmetric face. A significant interaction between T and P4/E2 for ratings success of the asymmetric face suggests that high levels of feminine T might be related to inter-sexual competition when conception risk is high.

Neurointermediate pituitary lobectomy decreases the incidence and severity of experimental autoimmune encephalomyelitis in Lewis rats.

Acute experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease of the central nervous system, mediated by T lymphocytes. Immunization of Lewis rats with myelin antigens suspended in complete Freund's adjuvant induces EAE. In a previous study on rats we have found that neurointermediate pituitary lobectomy (NIL) decreased both the humoral and cell-mediated immune responses. Here we investigated the effect of NIL on the incidence and severity of EAE and on the function of the hypothalamic-pituitary-adrenal axis in Lewis rats. NIL, hypophysectomized (Hypox) and sham-operated (Sham) rats were immunized s.c. with guinea-pig brain extract suspended in complete Freund's adjuvant. Untreated rats were used as controls. Water intake, body weight gain, clinical and histopathologic incidence and severity of EAE were evaluated in the operated groups. On killing, plasma adrenocorticotropin and corticosterone levels were measured and adrenals, thymuses and spleens were weighed. Histopathologic lesions were counted in the brain and spinal cord. Water intake and body weight gain were significantly decreased in Sham and Hypox animals with EAE whereas higher intakes persisted in the NIL group. Plasma levels of adrenocorticotropin were within the normal range whereas corticosterone levels increased in Sham and occasionally in NIL animals. Thymus weights were decreased in NIL and Hypox groups. The clinical and histopathologic incidence and severity of EAE were significantly decreased in NIL animals as compared with Sham and Hypox rats. We concluded that NIL affects the cell-mediated immune response and plays a role in the development and progression of EAE in the Lewis rat.

Vinclozolin modulates hepatic cytochrome P450 isoforms during pregnancy.

Vinclozolin (V) is classified as a potent endocrine disruptor. The aim of the present study was to determine the effects of V on rat liver CYP regulation and on serum levels of testosterone and estradiol during pregnancy. Pregnancy decreased the liver total CYP content by 65%, enzyme activities of MROD, PROD, and PNPH, and testosterone hydroxylation activities, as well as the protein content of CYP2A and 3A. V exposure remarkably induced the protein content and enzyme activities of CYP1A, 2A, 2B and 3A subfamilies. Testosterone and estradiol were affected in an opposite manner, provoking a 3.5-fold increase in the estradiol/testosterone ratio. These results suggest that V could regulate the hepatic CYP expression through interaction with receptors and coactivators involved in its expression and may play an important role in hormonal balance during pregnancy. In addition, the results may also contribute to understanding the toxicity of V by in utero exposure.

Waist-to-Hip Ratio, but Not Body Mass Index, Is Associated with Testosterone and Estradiol Concentrations in Young Women.

We studied if testosterone and estradiol concentrations are associated with specific female waist-to-hip ratios (WHRs) and body mass indices (BMIs). Participants were 187 young women from which waist, hips, weight, and height were measured. In addition, participants informed on which day of their menstrual cycle they were and provided a 6 mL saliva sample. Ninety-one of them were in the follicular phase and 96 in the luteal phase. Only in the fertile phase of the menstrual cycle we found a significant interaction between testosterone and estradiol affecting WHR (b ± s.e. = -0.000003 ± 0.000001; t 94 = -2.12, adjusted R (2) = -0.008, P = 0.03). Women with the highest levels of both hormones had the lowest WHRs, while women with low estradiol and high testosterone showed the highest WHRs. BMI significantly increased as testosterone increased in female in their nonfertile days.

Changes in Men's Salivary Testosterone and Cortisol Levels, and in Sexual Desire after Smelling Female Axillary and Vulvar Scents.

Several studies have shown that a woman's vaginal or axillary odors convey information on her attractivity. Yet, whether such scents induce psychoneuroendocrinological changes in perceivers is still controversial. We studied if smelling axillary and vulvar odors collected in the periovulatory and late luteal phases of young women modify salivary testosterone and cortisol levels, as well as sexual desire in men. Forty-five women and 115 men, all of them college students and unacquainted with each other, participated in the study. Female odors were collected on pads affixed to the axilla and on panty protectors both worn the entire night before experiments. Men provided five saliva samples, a basal one before the smelling procedure, and four more 15, 30, 60, and 75 min after exposure to odors. Immediately after smelling the odor source, men answered a questionnaire rating hedonic qualities of scents, and after providing the last saliva sample they answered questionnaire on sexual desire. We found that periovulatory axillary and vulvar odors increased testosterone and cortisol levels, with vulvar scents producing a more prolonged effect. Luteal axilla odors decreased testosterone and cortisol levels, while luteal vulva odors increased cortisol. Periovulatory axilla and vulva scents accounted for a general increase of interest in sex. These odors were also rated as more pleasant and familiar, while luteal vulvar odors were perceived as intense and unpleasant.