Maternal hyperandrogenism is associated with a higher risk of type 2 diabetes mellitus and overweight in adolescent and adult female offspring : a long‑term population‑based follow‑up study

Author’s accepted manuscript (postprint).This is an Accepted Manuscript of an article published by Springer in Journal of Endocrinological Investigation on 19/01/2022.Available online: https://link.springer.com/article/10.1007/s40618-021-01721-2acceptedVersio

Induction of a rat model of premature ovarian insufficiency using D-galactose feeding during the critical periods of development: A pilot study

Background: Premature ovarian insufficiency (POI) affects about 1% of women of reproductive ages (15-45 yr), with no curative treatment. Objective: We aimed to present a rat model of POI using a D-galactose enriched diet. Materials and Methods: In a pilot study, 4 pregnant Wistar rats were divided into 4 groups; 3 groups were fed galactose-enriched diets at days 3-15 of pregnancy (G1); on the 3rd day of pregnancy to parturition (G2), and the 3rd day of pregnancy until the end of the weaning period (G3). Also, group 4, as the control group (G0), was fed standard pellets during the study. After confirming the lack of adverse effects of dieting with galactose in terms of offsprings’ birth weight, we performed our study designed the same as the pilot study. A total of 40 pregnant Wistar rats were randomly divided into 4 groups. Ovarian histology, reproductive hormones, and immunological characteristics of the female offspring were examined in all experimental groups and compared. Results: The pilot study revealed no significant differences in the birth weight of the offspring of the 4 study groups (p = 0.96). The ovarian index in the female offspring of those with a gal-exposed diet was significantly lower than that of the control group offspring (p < 0.01). Conclusion: As the birth weights of the offspring of our experimental and control groups were similar, it can be concluded that the reduction of ovarian follicles after prenatal exposure to D-galactose is due to the ovotoxicity of galactose. The results of our final study will provide more information about the rat POI model induced by prenatal exposure to D-galactose. Key words: Premature ovarian insufficiency, Animal model, D-galactose

Evaluation of Cardiac Hemodynamic Parameters Following Ischemia-Reperfusion Injury in a Rat Model of Polycystic Ovary Syndrome

Introduction: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women during reproductive ages. This syndrome is associated with disruption of sex hormone levels. Studies have shown that endurance of the heart to ischemia-reperfusion (I/R) injury can be affected by sex hormones. In the present study, the rate of cardiac tolerance against I/R injury in the PCOS rat model was compared with normal (control) rats. Materials and Methods: The rats were randomly divided into two groups; PCOS and control (n=8 per group). The hearts were isolated in Langendorff isolated heart system. Cardiac perfusion was performed in a retrograde flow in the aorta at constant pressure (75 mmHg) by Krebs-Henslit buffer. A pressure (5-10 mmHg) was put to the left ventricle, using an intraventricular balloon, to measure the hemodynamic parameters of the heart. Cardiac signals were recorded while being transmitted through the catheter to the Powerbull system. Results: Before I/R, the values for cardiac hemodynamic parameters including HR, LVDP, RPP and ± dp/dt, increased in the rat model of PCOS compared to controls, although these increases were not statistically significant (P>0.05). These parameters had decreasing trends after I/R in PCOS rats compared to controls which were not statistically significant (P>0.05). Conclusion: Cardiac resistance to I/R injury was found to be similar in both PCOS and control animals, which could be due to the cardioprotective role of sex hormones such as estrogens

The effects of testosterone intrauterine disturbance on sperm quality and testis tissue in male rat\'s offspring after puberty

Background: Environmental factors and hormonal disorders during prenatal life can impair the evolution and differentiation of fetus&rsquo;s reproductive system. The aim of this study was to the examination of sperm quality and testis tissue in adult rats that had exposed to exogenous testosterone during their prenatal life. Materials & Methods: Pregnant rats divided into two experimental and control groups. In experimental group, pregnant rats daily were subcutaneously injected with 3 mg exogenous testosterone during gestational days 16-19, and controls received solvent. The reproductive system was examined in male offspring of these animals after puberty. Data analysis was performed by using the SPSS software (version 15). Distributions between groups are compared by using the Mann-Whitney test. Results: In the offspring of experimental group, motility and the number of sperm were significantly decreased (P<0.05). No morphological abnormality was observed in sperm in two groups. The numbers of sertoli cells, ratios of spermatocyte and round spermatid cells were significantly decreased in the offspring of experimental group (P<0.05). No significant difference was observed in seminiferous tubules diameter between the two groups. Serum testosterone levels were significantly decreased in offspring from experimental group (P<0.05). Conclusion: The present study showed that prenatal exposure to testosterone leads to decrease of sperm quality and changes in testis tissue in male rats, after puberty

Induced premature ovarian insufficiency by using D galactose and its effects on reproductive profiles in small laboratory animals: a systematic review

Abstract Background Development of a hyper-gonadotropic hypoestrogenism condition in women < 40 years, defined as premature ovarian insufficiency (POI), is the most common long-term complication in female survivors of galactosemia. In this systematic review, summarize the galactose (GAL) induced POI in rat and mice models. Methods For this systematic review, we conducted a search of case control studies published from 1990 until August 2018 in PubMed/Medline, and Web of science, using the descriptors in the title/abstract field. A ‘pearl growing’ strategy was employed whereby, after obtaining the full text articles, reference lists of all included studies (n = 14) were reviewed for additional publications that could be used. Results We selected and categorized 14 studies according to the time of exposure to GAL into two groups of prenatal (n = 4) and postnatal (n = 10). Findings of these studies showed that the different stages of follicular development are targeted differently by galactose exposure during the prenatal and postnatal periods: The small follicles (primordial and primary follicles) are targeted by galactose toxicity during prenatal exposure and the pre-antral and antral follicles are targeted by galactose toxicity during postnatal exposure. Conclusions This systematic review shows that galactose has an ovotoxicity effect that can be used to induce appropriate POI animal models only if sufficient doses, proper onset time, and duration of prenatal exposure are taken into account. An optimized model of POI induction should manifest all the required ovarian morphological, hormonal, and estrus cycle changes

Effects of Rosa damascena on reproductive improvement, metabolic parameters, liver function and insulin-like growth factor-1 gene expression in estradiol valerate induced polycystic ovarian syndrome in Wistar rats

Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-age women. The present study aimed to evaluate the effects of Rosa damascena (RD) extract in estradiol valerate (EV) induced polycystic ovary syndrome rats. Methods: Adult female Wistar rats were divided into control (n = 12) and PCOS groups (n = 36). The PCOS model was induced using EV (4 mg/kg/day), which was confirmed in 6 rats in each control and PCOS group by observation of irregular estrous cycles in vaginal smears and ovarian multiple cystic. Then, the rest of the control group (n = 6) and PCOS rats (n = 30 in 5 divided groups) were treated orally for 28 days with metformin (MET) as a positive control (200 mg/kg/day) and RD extract (400, 800, and 1200 mg/kg/day, respectively). Body and ovary weights, biochemical and histological parameters, and expression of the IGF-1 gene were measured. Results: Compared to the PCOS group, metformin and higher doses of RD extract (800 and 1200 mg/kg/day) significantly reduced BW, HOMA-IR, FBS, FINS, TG, LDL, TT, E2, LH, TC, and liver enzymes, and increased HDL and FSH levels. In addition, ovarian weight and CFs decreased, and the findings showed an increment in PFs, CLs, PAFs, AFs, and GFs. IGF-1 gene expression levels were significantly decreased (p < 0.001). Conclusion: RD extract seems to have the potential therapeutic effect of alleviating PCOS complications, and IGF-1 signaling may be involved in the beneficial effects of RD on PCOS

To what extent the weight changes impact the risk of hypertension among menopausal women: insights from Tehran lipid and glucose study

Abstract Background & aim The association between weight change and incident hypertension (HTN) in menopausal women has not been well characterized. This study aimed to determine whether weight changes after menopausal years make a difference in incidents of hypertension. Materials & methods This population-based study was performed using data collected from Tehran Lipid and Glucose Study cohort (1999–2018). Women who had natural and early menopause were followed up every 3 years. Data gathering was performed through the standard protocol of the study. Statistical analysis was performed using multivariable Cox hazard regression analysis. We used the ‘survival’ package in the R software version 3.6.0 to fit survival models. Results A total of 487 menopausal women met the inclusion criteria; 62.6% had natural menopause and remained had early menopause. Among the participants, 65.5% experienced HTN. The highest proportion of participants had > 5% weight gain, while the lowest had 3–5% weight gain. Either losing body weight (lost > 5%: HR: 0.44; CI 95%, 0.32, 0.62; p  5% (HR: 0.69; CI 95%, 0.51, 0.91; p = 0.01), were associated with decreased risk of HTN after adjustment for confounders. In this study, weight loss and gain have a protective impact on the development of HTN in subjects. For incident HTN, age (HR: 1.04 (1.01, 1.08), p = 0.004), fasting blood glucose (HR: 1.01, CI 95%:1.00, 1.01; p < 0.001), body mass index (1.02 (1.00, 1.05), p = 0.03) and smoking (1.70 (1.11, 2.58), p = 0.01) were positively associated with HTN. Conclusions Our study indicates the significant association of weight change with hypertension risk in later life among menopausal women

Prenatal Testosterone Exposure Worsen the Reproductive Performance of Male Rat at Adulthood

<div><p>The reproductive system is extremely susceptible to environmental insults, for example exogenous steroids during gestational development and differentiation. Experimental induction of androgen excess during prenatal life in female animal models reprograms their reproductive physiology, however the fetal programming of the male reproductive system by androgen excess has not been well studied. We aimed to determine the effect of prenatal exposure of two different doses of testosterone on different gestational days, on the male reproductive system using a rat model. Sixteen pregnant rats were randomly divided into two experimental groups and two control groups. Experimental group І were subcutaneously injected with 3 mg free testosterone on gestational days 16-19 and its controls received solvent for that time; experimental group П were subcutaneously injected with 20 mg free testosterone on day 20 of gestational period and its controls received solvent at the same time. The reproductive system morphology and function of 32 male offspring of these study groups were compared at days 6-30-60 of age and after puberty. The anogenital distance of the male offspring of both experimental groups had no significant differences on the different days of measurement, compared with controls. In the offspring of experimental group І, the testes weight, number of Sertoli, Spermatocyte and Spermatid cells, sperm count and motility and the serum concentration of testosterone after puberty were significantly decreased; except for reduction of sperm motility (p< 0.01), the other effects were not observed in the offspring of experimental group ІІ. In summary, our data show that prenatal exposure of male rat fetuses to excess testosterone disrupted reproductive function, an effect highly dependent on the time, duration and level of exposure. It seems that the reproductive system in individuals exposed to high levels of androgens during fetal life should be evaluated at puberty and likely to be treated.</p> </div

Reproductive assessment: Findings from 20 years of the Tehran Lipid and Glucose Study

Context: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. Evidence Acquisition: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. Results: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. Conclusions: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines

Reproductive Assessment: Findings from 20 Years of the Tehran Lipid and Glucose Study

Context: Reproductive domains of the Tehran lipid and glucose study (TLGS) are unique in that they provide reliable information on reproduction of an urban population of West Asia. The aim of this review is to present the most important reproductive findings of TLGS. Evidence Acquisition: This review is summarizing all articles published in the context of reproductive aspects of TLGS results over the 20-year follow-up. A comprehensive databases search was conducted in PubMed (including Medline), Web of Science and Scopus for retrieving articles on the reproductive histories in context of the TLGS. Results: The mean (SD) age at menarche and menopause was 13 (1.2) and 49.6 (4.5) years respectively. While pills were the most commonly used modern methods at the initiation of TLGS, the prevalence of condoms rose sharply and significantly over the follow up duration. Among women with history of gestational diabetes, the risk of diabetes and dyslipidemia progression were 2.44 and 1.2 fold higher than others. Prevalences of PCOS and idiopathic hirsutism among reproductive age participants of TLGS were 8.5% (95% CI: 6.8% - 10.2%) and 13.0% (95% CI: 10.9% - 15.1%), respectively. Trend of cardio-metabolic risk factors among women with PCOS showed that there were no statistically significant differences between mean changes of each cardio metabolic variables between PCOS and healthy women; PCOS status also significantly associated with increased hazard of diabetes and prediabetes among women aged younger than 40 years (HR: 4.9; 95% CI: 2.5 - 9.3, P value < 0.001)) and (HR: 1.7; 95% CI: 1.1 - 2.6), P value < 0.005), respectively. Conclusions: The population based nature of TLGS provides a unique opportunity for valid assessment of reproductive issues, the results of which could provide new information for modification of existing guidelines