A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits

We tested the hypothesis that genes encoded on the sex chromosomes play a direct role in sexual differentiation of brain and behavior. We used mice in which the testis-determining gene (Sry) was moved from the Y chromosome to an autosome (by deletion of Sry from the Y and subsequent insertion of an Sry transgene onto an autosome), so that the determination of testis development occurred independently of the complement of X or Y chromosomes. We compared XX and XY mice with ovaries (females) and XX and XY mice with testes (males). These comparisons allowed us to assess the effect of sex chromosome complement (XX vs XY) independent of gonadal status (testes vs ovaries) on sexually dimorphic neural and behavioral phenotypes. The phenotypes included measures of male copulatory behavior, social exploration behavior, and sexually dimorphic neuroanatomical structures in the septum, hypothalamus, and lumbar spinal cord. Most of the sexually dimorphic phenotypes correlated with the presence of ovaries or testes and therefore reflect the hormonal output of the gonads. We found, however, that both male and female mice with XY sex chromosomes were more masculine than XX mice in the density of vasopressin-immunoreactive fibers in the lateral septum. Moreover, two male groups differing only in the form of their Sry gene showed differences in behavior. The results show that sex chromosome genes contribute directly to the development of a sex difference in the brain

Specific Activation of Estrogen Receptor Alpha and Beta Enhances Male Sexual Behavior and Neuroplasticity in Male Japanese Quail

Two subtypes of estrogen receptors (ER), ERα and ERβ, have been identified in humans and numerous vertebrates, including the Japanese quail. We investigated in this species the specific role(s) of each receptor in the activation of male sexual behavior and the underlying estrogen-dependent neural plasticity. Castrated male Japanese quail received empty (CX) or testosterone-filled (T) implants or were daily injected with the ER general agonist diethylstilbestrol (DES), the ERα-specific agonist PPT, the ERβ-specific agonist DPN or the vehicle, propylene glycol. Three days after receiving the first treatment, subjects were alternatively tested for appetitive (rhythmic cloacal sphincter movements, RCSM) and consummatory aspects (copulatory behavior) of male sexual behavior. 24 hours after the last behavioral testing, brains were collected and analyzed for aromatase expression and vasotocinergic innervation in the medial preoptic nucleus. The expression of RCSM was activated by T and to a lesser extent by DES and PPT but not by the ERβagonist DPN. In parallel, T fully restored the complete sequence of copulation, DES was partially active and the specific activation of ERα or ERβ only resulted in a very low frequency of mount attempts in few subjects. T increased the volume of the medial preoptic nucleus as measured by the dense cluster of aromatase-immunoreactive cells and the density of the vasotocinergic innervation within this nucleus. DES had only a weak action on vasotocinergic fibers and the two specific ER agonists did not affect these neural responses. Simultaneous activation of both receptors or treatments with higher doses may be required to fully activate sexual behavior and the associated neurochemical events

Efficacy and patient satisfaction after NovaSure and Minerva endometrial ablation for treating abnormal uterine bleeding: a retrospective comparative study

Constantine Scordalakes,1 Robert delRosario,2 Andrew Shimer,3 Russell Stankiewicz4 1Women’s Health Care, P.C., Newburgh, IN, 2Partners in Women’s Healthcare, Lemoyne, PA, 3Craig Ranch OB-GYN, McKinney, TX, 4OB-GYN of Evangelical, Lewisburg, PA, USA Objective: Compare amenorrhea rate, menstrual symptoms, patient satisfaction, and adverse events in women who underwent endometrial ablation with the NovaSure versus the Minerva radiofrequency ablation systems.Methods: We surveyed 189 premenopausal women (mean 40.8±6.2 years old) who underwent endometrial ablation for abnormal uterine bleeding using the NovaSure (n=97) or Minerva (n=92) systems, at four private US gynecology clinics, and whose procedure date was after July 2015 with follow-up ≥3 months. Women were surveyed an average of 11.3±3.9 months (range 137–532 days) after ablation.Results: The subject-reported amenorrhea rate was 52% higher in NovaSure subjects than Minerva subjects (64% and 42%, respectively; p=0.004). Age and bleeding cyclicity did not affect amenorrhea rate in either group. Normal-to-no bleeding was reported by >90% of subjects after either treatment. NovaSure was significantly more effective than Minerva at reducing pad/tampon use in women with any residual bleeding (2.4±5.2 items/day versus 4.7±5.5 items/day, p=0.049). NovaSure was significantly more effective than Minerva at reducing premenstrual syndrome (PMS) symptoms (p=0.019) and menstrual pain (p=0.003), and more NovaSure subjects (94%) than Minerva subjects (78%) were satisfied with clinical outcomes (p=0.003). Adverse events did not differ by treatment; three women in each group progressed to hysterectomy.Conclusion: While overall bleeding reduction in premenopausal women with abnormal uterine bleeding was excellent with either endometrial ablation system, NovaSure treatment resulted in a higher patient-reported 1-year amenorrhea rate, and women with residual bleeding used fewer pads and tampons than Minerva-treated women. Additionally, NovaSure subjects reported better menstrual-related life quality and PMS symptom alleviation, and greater satisfaction with outcomes than Minerva-treated women. Keywords: endometrial ablation, abnormal uterine bleeding, NovaSure, Minerva, premenopausal, satisfactio

Lack of functional estrogen receptor ␤ gene disrupts pubertal male sexual behavior

Abstract The estrogen receptor-␤ (ER␤) mediates estrogen action in the female gonads, reproductive tract, and central nervous system. In addition, in rats and mice, gonadotropin-releasing hormone (GnRH-I) neurons coexpress ER␤. Here we asked if ER␤ plays a role in the onset of puberty and in hypothalamic-pituitary-gonadal (HPG) axis function in male mice. We examined mating behavior, testosterone concentrations, steroid negative feedback on gonadotropins, and GnRH-I function in male ER␤ knockout (ER␤KO) and wild-type (WT) mice. Peripubertal ER␤KO males displayed their first ejaculation at a significantly older age than WT littermates. Castrated, adult ER␤KO mice had significantly higher plasma luteinizing hormone (LH) than WT counterparts. Estradiol (E2) treatment reduced LH and follicle stimulating hormone (FSH) concentrations to an equivalent degree in castrates of both genotypes. In three different measures of the adult GnRH-I system, no genotypic differences were observed. These data show that ER␤ plays an important role in the timing of male sexual behavior at puberty, but does not appear to be involved in adult HPG axis functioning. Furthermore, our data suggest that a primary role of ER␤ may be to regulate ejaculatory behavior