Gonadal characterization of the Amazonian fish Serrapinnus kriegi (Characidae: Cheirodontinae)

The knowledge of the testicular and ovarian morphology of a particular fish species is of paramount importance. Such analyze enables the development of studies and techniques aiming the improvement of their reproduction, management, commercialization and even their conservation. This study performed the ovarian and testicular characterization of the ornamental Amazon fish Serrapinnus kriegi. A total of three males and three females had their gonads analyzed by optical microscopy. Females present ovaries filled with oocytes in asynchronous development, indicating partial spawning in the species. Moreover, the micropyle and micropilar cell formation was observed in primary growing oocytes, representing a precocious oocyte development; and the zona radiata in the final vitellogenic oocytes is thicker than other related species, evidencing the development of a better protection to the embryos in function of the waters’ turbulence that characterize it spawning sites in the Amazonian streams. The male specimens’ present anastomosed tubular testes with unrestricted spermatogonia spread along the entire seminiferous tubules. The present data elucidate the dynamic of spermatogenesis and oogenesis of an ornamental Amazonian species, through the description of the male and female germ cells development.

Deconstructing a Syndrome: Genomic Insights into PCOS Causal Mechanisms and Classification

Polycystic ovary syndrome (PCOS) is among the most common disorders of reproductive-age women, affecting up to 15% worldwide, depending on the diagnostic criteria. PCOS is characterized by a constellation of interrelated reproductive abnormalities including disordered gonadotropin secretion, increased androgen production, chronic anovulation, and polycystic ovarian morphology. It is frequently associated with insulin resistance and obesity. These reproductive and metabolic derangements cause major morbidities across the lifespan, including anovulatory infertility and type 2 diabetes (T2D). Despite decades of investigative effort, the etiology of PCOS remains unknown. Familial clustering of PCOS cases has indicated a genetic contribution to PCOS. There are rare Mendelian forms of PCOS associated with extreme phenotypes, but PCOS typically follows a non-Mendelian pattern of inheritance consistent with a complex genetic architecture, analogous to T2D and obesity, that reflects the interaction of susceptibility genes and environmental factors. Genomic studies of PCOS have provided important insights into disease pathways and have indicated that current diagnostic criteria do not capture underlying differences in biology associated with different forms of PCOS. We provide a state-of-the-science review of genetic analyses of PCOS, including an overview of genomic methodologies aimed at a general audience of non-geneticists and clinicians. Applications in PCOS will be discussed, including strengths and limitations of each study. The contributions of environmental factors, including developmental origins, will be reviewed. Insights into the pathogenesis and genetic architecture of PCOS will be summarized. Future directions for PCOS genetic studies will be outlined.

Effect of Electroacupuncture on Reproductive Disorders and Insulin Resistance in a Murine Polycystic Ovary Syndrome Model

Polycystic ovarian syndrome (PCOS) is a common, complex, and heterogeneous endocrine and metabolic disorder. There is no standardized treatment, and it therefore requires individualized therapies according to the symptoms and pathogenesis of each patient. The present study aimed to determine the effect of electroacupuncture at the acupoints Zusanli (ST36), Sanyinjiao (SP6), and Neiguan (PC6) on reproductive disorders and insulin resistance in a murine model of PCOS induced by dehydroepiandrosterone (DHEA). Vaginal smear analysis was used to determine mice estrous cycle; intraperitoneal glucose and insulin tolerance tests were adopted to analyze metabolic characteristics; enzyme-linked immunosorbent assay was used to measure hormone levels; gene expression was quantified with real-time PCR; hematoxylin and eosin staining was used to observe ovarian morphology. We observed disordered estrous cycle, polycystic ovarian morphology, and higher levels of homeostasis model assessment-insulin resistance (HOMA-IR) and testosterone (T), indicating successful modeling of PCOS. DHEA increased levels of estrogen (E2), progesterone (P), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), and EA treatment restored them to levels seen in the control group. EA reduced the days in estrus caused by DHEA, improved the abnormal sex hormone receptor genes, and attenuated the DHEA-induced histomorphological changes in mouse ovaries. The average expressions of the androgen receptor (AR), estrogen receptor (ER), luteinizing hormone receptor (LHR), and follicle-stimulating hormone receptor (FSHR) genes in the ovary greatly increased after DHEA treatment and significantly decreased in the DHEA + EA group. After EA treatment, the cystic follicle (CF) number was reduced and corpora lutea (CL) increased in the DHEA + EA group compared to the DHEA group. EA improved glucose intolerance and insulin intolerance. Statistical analysis of intraperitoneal glucose tolerance test-area under curve (IPGTT-AUC) glucose levels revealed a significant decrease in DHEA group mice compared to the control and DHEA + EA groups. EA was found to restore fasting blood glucose, fasting serum insulin, and HOMA-IR. In summary, our study suggests that EA has a remarkable effect in the DHEA-induced murine PCOS model. Management of EA could improve estrous cycle, hormonal disorders, abnormal sex hormone receptors in ovaries, ovary morphology, and insulin resistance in PCOS mice.

Challenges in Establishing a Relevant Model of Polycystic Ovary Syndrome in Rats – A Mini Review

Polycystic ovary syndrome (PCOS) is one of the most com-mon female endocrinopathy and one of the leading causes of in-fertility. However, the exact etiopathogenetic mechanisms are not discovered yet, while therapeutic strategies in PCOS commonly rely on symptomatic rather than curative. Regarding reasonable ethical limitations in human population, animal experimental studies can provide better insights into mechanisms underlying etiopathogenesis of PCOS, as well as investigations of different therapeutic strategies. Rodent models for PCOS are very useful for experimental studies due to their great genetic similarities with human genome, short reproductive and life span, feasible gener-ating of genetically adapted animals, and convenient and acces-sible use. To our knowledge, androgens (dehydroepiandroste-rone, testosterone propionate, 5a-dihydrotestosterone), as well as estradiol valerate, represent the most frequently used hormones for PCOS modeling. Furthermore, the administration of antipro-gesterone or letrozole has been reported as effective for PCOS induction. In our review, the presented PCOS models were ac-complished by the administration of different hormones or drugs and alterations of environment. The main focus of this review was to summarize the alterations in ovarian morphology, hypotha-lamic-pituitary-ovarian axis, and hormone levels across above-mentioned protocols for postnatal PCOS modeling in rats.

Metabolic Syndrome in Polycystic Ovary Syndrome

Polycystic ovary syndrome (PCOS) is a common endocrinopathy in women of reproductive age. Although its essential clinical manifestation includes a plethora of symptoms and signs, which largely reflects the underlying hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, PCOS may also be associated with many metabolic derangements. These metabolic derangements happen to overlap with many of the core constituents of the metabolic syndrome (MBS)—increased insulin resistance, central obesity, and dyslipidemia. The two disorders also display similarly increased risks for certain metabolic and vascular diseases, such as type 2 diabetes mellitus, hypertension, and cardiovascular diseases. Due to the many similarities between metabolic syndrome and PCOS, this review aims to examine the evidence concerning the overlapping features, the risks for comorbidities, possible shared mechanisms, and treatment strategies in patients with coexisting PCOS and MBS.

NORMOTENSIVE RATS WITH PCOS EXHIBIT THE HYPERTENSIVE PATTERN: FOCUS ON OXIDATIVE STRESS

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. We aimed to investigate the potential strain differences in ovarian morphology, hemodynamic and biochemical characteristics in an androgen-induced PCOS rat model. A total of 3 weeks old 24 rats (12 Wistar Kyoto - WK and 12 Spontaneously Hypertensive Rats – SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily subcutaneous injections of testosterone-enanthate (1 mg/100 g body weight (BW)) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic and cystic follicles). Ultrasonographycally, a significant decrease in ovarian volume (OV) was registered in PCOS groups, but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, TBARS and O2- were higher in both strains, while SOD and GSH were significantly lowered.

Polycystic ovarian syndrome: current understanding of pathogenesis, diagnosis and treatment

Review article is devoted to one of the most common polygenic endocrinopathies in women of reproductive age, polycystic ovarian syndrome (PCOS). We review the current criteria used to make a correct diagnosis based on four phenotypes of PCOS: Frank (phenotype A) – biochemical and/or clinical hyperandrogenism, oligo-/anovulation, polycystic ovarian morphology according to ultrasound; anovulatory (phenotype B) – oligo-/anovulation, biochemical and/or clinical hyperandrogenism; ovulatory (phenotype C) – biochemical and/or clinical hyperandrogenism, polycystic ovarian morphology according to ultrasound; non-androgenic (phenotype D) – oligo-/anovulation, polycystic ovarian morphology according to ultrasound. This article presents the main theories of PCOS pathogenesis: peripheral, central, insulin, genetic, and also considers epigenetic factors. PCOS is a multifactorial disease in which genes are responsible for the mechanisms of the process, and environmental factors through epigenetics affect the genetic material. PCOS phenotypes play an important role in clinical practice, as they allow an individualised approach to the selection of therapy in each case, taking into account the pathogenesis of the disease and predicting its course in the future. The main therapeutic options for treating patients with PCOS, taking into account the multifactorial nature of the disease and the patient's interest in pregnancy, are reviewed. The article presents modern methods for the correction of hyperandrogenism and anovulation, with special emphasis on the need for progesterone therapy.

Effect of the spatial–temporal specific theca cell Cyp17 overexpression on the reproductive phenotype of the novel TC17 mouse

Background In the ovarian follicle, the Theca Cells (TCs) have two main functions: preserving morphological integrity and, importantly, secreting steroid androgen hormones. TCs express the essential enzyme 17α-hydroxylase/17,20-desmolase (CYP17), which permits the conversion of pregnenolone and progesterone into androgens. Dysregulation of CYP17 enzyme activity due to an intrinsic ovarian defect is hypothesized to be a cause of hyperandrogenism in women. Androgen excess is observed in women with polycystic ovary syndrome (PCOS) resulting from excess endogenous androgen production, and in transgender males undergoing exogenous testosterone therapy after female sex assignment at birth. However, the molecular and morphological effects of Cyp17 overexpression and androgen excess on folliculogenesis is unknown. Methods In this work, seeking a comprehensive profiling of the local outcomes of the androgen excess in the ovary, we generated a transgenic mouse model (TC17) with doxycycline (Dox)-induced Cyp17 overexpression in a local and temporal manner. TC17 mice were obtained by a combination of the Tet-dependent expression system and the Cre/LoxP gene control system. Results Ovaries of Dox-treated TC17 mice overexpressed Cyp17 specifically in TCs, inducing high testosterone levels. Surprisingly, TC17 ovarian morphology resembled the human ovarian features of testosterone-treated transgender men (partially impaired folliculogenesis, hypertrophic or luteinized stromal cells, atretic follicles, and collapsed clusters). We additionally assessed TC17 fertility denoting a perturbation of the normal reproductive functions (e.g., low pregnancy rate and numbers of pups per litter). Finally, RNAseq analysis permitted us to identify dysregulated genes (Lhcgr, Fshr, Runx1) and pathways (Extra Cellular Matrix and Steroid Synthesis). Conclusions Our novel mouse model is a versatile tool to provide innovative insights into study the effects of Cyp17 overexpression and hyperandrogenism in the ovary.