Kiss1 expression in the hypothalamic arcuate nucleus is lower in dairy cows of reduced fertility

We tested the hypothesis that divergent genetic merit for fertility of dairy cows is due to aberrant reproductive neuroendocrine function. The kisspeptin status of non-pregnant cows of either positive (POS) or negative (NEG) breeding values for fertility was studied in 3 groups (n = 8), based on their previous post-partum period: POS cows which had spontaneous ovarian cycles (POS-CYC) and NEG cows which either cycled (NEG-CYC) or did not cycle (NEG-NONCYC). Ovarian cycles were synchronized, blood samples were taken to define endocrine status and the animals were slaughtered in an artificial follicular phase. The brains and the pituitary glands were collected for quantitative polymerase chain reaction (qPCR) and in situ hybridisation (ISH) of hypothalamic GNRH1, Kiss1, TAC3 and PDYN and pituitary expression of LHB and FSHB. Gonadotropin releasing hormone (GnRH) and kisspeptin levels were quantified in snap frozen median eminentes (ME). GNRH1 expression and GnRH levels in the ME were similar across groups. Kiss1 expression in the preoptic area of the hypothalamus was also similar across groups, but Kiss1 in the arcuate nucleus was almost 2-fold higher in POS-CYC cows than in NEG groups. TAC3 expression was higher in POS-CYC cows. The number of pituitary gonadotropes and the level of expression of LHB and FSHB was similar across groups. We conclude that the lower levels of Kiss1 and TAC3 in NEG cows with low fertility status, and may lead to deficient GnRH and gonadotropin secretion.

Biochemical criteria for the development mechanisms of various reproduction disorders in dairy cows

Ventsova I, Safonov V. 2021. Biochemical criteria for the development mechanisms of various reproduction disorders in dairy cows. Biodiversitas 22: 4997-5002. The article presents the evaluation of peroxide, antioxidant, and hormonal conditions of high-producing red-and-white dairy cows in the physiological and pathological course of pregnancy and the postpartum period. The blood concentration of malonic dialdehyde, stable nitric oxide metabolites, S-nitrosothiols, vitamins E and C, carotin, gonadal, corticosteroid, and thyroid hormones, as well as activity of GPx, GR, SOD, catalase, and ceruloplasmin, were estimated to define major disorder-provoking factors. Analysis of the data shows that ketosis-gestosis syndrome during pregnancy, postpartum metritis, and gonadal dysfunction occur mainly because of oxidative stress in the context of unbalanced peroxide responses and antioxidant protection. Levels of malonic dialdehyde compared to healthy animals increased by 42.3%, 75%, 56.6%, respectively, as also enzyme activities of GR by 26%, 68.1%, 30.1% and catalase by 17.3%, 45.1%, and 23.9%, correspondingly. The endocrine status indicators in the animals with ketosis-gestosis syndrome changed as follows: progesterone levels were 29.5% lower in cows, 17?-estradiol and cortisol were 20.8% and 14.7% lower, respectively. In animals with inflammatory uterine diseases and depressing reproductive glands, progesterone level was 2 and 3 times lower than in healthy animals, the content of cortisol was 17.6% and 25.1% lower, and testosterone decreased by 21.4% and 75.1%, respectively.

The immunotherapy candidate TNFSF4 may help the induction of a promising immunological response in breast carcinomas

Immune checkpoint blockade, an immunotherapy, has been applied in multiple systemic malignancies and has improved overall survival to a relatively great extent; whether it can be applied in breast cancer remains unknown. We endeavored to explore possible factors that may influence immunotherapy outcomes in breast cancer using several public databases. The possible treatment target TNF superfamily member 4 (TNFSF4) was selected from many candidates based on its abnormal expression profile, survival-associated status, and ability to predict immune system reactions. For the first time, we identified the oncogenic features of TNFSF4 in breast carcinoma. TNFSF4 was revealed to be closely related to treatment that induced antitumor immunity and to interact with multiple immune effector molecules and T cell signatures, which was independent of endocrine status and has not been reported previously. Moreover, the potential immunotherapeutic approach of TNFSF4 blockade showed underlying effects on stem cell expansion, which more strongly and specifically demonstrated the potential effects of applying TNFSF4 blockade-based immunotherapies in breast carcinomas. We identified potential targets that may contribute to breast cancer therapies through clinical analysis and real-world review and provided one potential but crucial tool for treating breast carcinoma that showed effects across subtypes and long-term effectiveness.

Interaction of the (CAG)n polymorphism in the androgen receptor gene and oral con-traceptive use on moral judgement in women

Biological factors including genetic variation are contributors to differences in moral deci-sions. Recently, Gong et al. (2017) reported that female carriers of more shorter alleles of the functional (CAG)n polymorphism in the androgen receptor (AR) gene showed enhanced en-dorsement of harmful actions. We aimed to replicate and extend these findings. N = 155 healthy young adults of Western European/German origin were genotyped for the AR (CAG)n polymorphism and completed a set of moral dilemmas that are designed to allow an estimation of underlying utilitarian and deontological tendencies in addition to the tradition-al moral score. While AR (CAG)n genotype did not affect moral judgement in men, there were (CAG)n × endocrine status interactions in the female sample, particularly on deontolo-gy. Women using oral contraceptives who carried two short (CAG)n alleles had reduced lev-els of deontology compared to carriers of long (CAG)n alleles. Descriptively, the opposite pattern emerged for free cycling women. The findings underscore the importance of andro-genic function for moral judgement and highlight the modulatory role of exogenous steroids.

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.

CLINICAL COURSE OF PERIMENOPAUSAL PERIOD IN WOMEN WITH HYPERANDROGENISM SYNDROME

Hyperandrogenism is a disorder of endocrine status caused by excess production of androgens. The syndrome is a consequence of increased androgen production both in the ovaries and adrenal glands. However, such a division is very arbitrary, as increased production of androgens in the adrenal glands may increase production in the ovaries and vice versa. Androgens in women are synthesized by ovaries, adrenal glands and peripheral tissues, which also participate in metabolism.The set of androgens in both womenand men includes dehydroepiandrosterone-sulfate, dehydroepiandrosterone, androstenedione, testosterone and 5-alpha-dihydrotestosterone (5-alpha-DHT). Still, unlike men, women have a higher concentration of the first three hormones than the lasttwo. Androgen synthesis in the adrenal glands in women is regulated by adrenocorticotropic and in the ovaries by luteinizing hormone (LH) and some other intraglandular autoparacrine mechanisms. According to recent studies, in addition to the basic biological, previously commonly known effects of androgens, their new mechanisms of influence on the female body have been discovered. Keywords: hyperandrogenism, hormones, ovaries, adrenal glands, reproductive disorders