scholarly journals Effect of androgen treatment during foetal and/or neonatal life on ovarian function in prepubertal and adult rats

Reproduction ◽  
2012 ◽  
Vol 143 (1) ◽  
pp. 21-33 ◽  
Author(s):  
Victoria Tyndall ◽  
Marie Broyde ◽  
Richard Sharpe ◽  
Michelle Welsh ◽  
Amanda J Drake ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Polycystic Ovary ◽  
Time Windows ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Female Rats ◽  
Postnatal Life ◽  
Adult Rats ◽  
Stromal Compartment ◽  
Neonatal Life

We investigated the effects of different windows of testosterone propionate (TP) treatment during foetal and neonatal life in female rats to determine whether and when excess androgen exposure would cause disruption of adult reproductive function. Animals were killed prepubertally at d25 and as adults at d90. Plasma samples were taken for hormone analysis and ovaries serial sectioned for morphometric analyses. In prepubertal animals, only foetal+postnatal and late postnatal TP resulted in increased body weights, and an increase in transitory, but reduced antral follicle numbers without affecting total follicle populations. Treatment with TP during both foetal+postnatal life resulted in the development of streak ovaries with activated follicles containing oocytes that only progressed to a small antral (smA) stage and inactive uteri. TP exposure during foetal or late postnatal life had no effect upon adult reproductive function or the total follicle population, although there was a reduction in the primordial follicle pool. In contrast, TP treatment during full postnatal life (d1–25) resulted in anovulation in adults (d90). These animals were heavier, had a greater ovarian stromal compartment, no differences in follicle thecal cell area, but reduced numbers of anti-Mullerian hormone-positive smA follicles when compared with controls. Significantly reduced uterine weights lead reduced follicle oestradiol production. These results support the concept that androgen programming of adult female reproductive function occurs only during specific time windows in foetal and neonatal life with implications for the development of polycystic ovary syndrome in women.

scholarly journals Subfertility in androgen-insensitive female mice is rescued by transgenic FSH

2017 ◽  
Vol 29 (7) ◽  
pp. 1426 ◽  
Author(s):  
K. A. Walters ◽  
M. C. Edwards ◽  
M. Jimenez ◽  
D. J. Handelsman ◽  
C. M. Allan
Keyword(s):  
Androgen Receptor ◽  
Litter Size ◽  
Ovarian Function ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Female Fertility ◽  
Wild Type ◽  
Female Reproduction ◽  
Androgen Insensitivity ◽  
Female Mice

Androgens synergise with FSH in female reproduction but the nature of their interaction in ovarian function and fertility is not clear. In the present study, we investigated this interaction, notably whether higher endogenous FSH can overcome defective androgen actions in androgen receptor (AR)-knockout (ARKO) mice. We generated and investigated the reproductive function of mutant mice exhibiting AR resistance with or without expression of human transgenic FSH (Tg-FSH). On the background of inactivated AR signalling, which alone resulted in irregular oestrous cycles and reduced pups per litter, ovulation rates and antral follicle health, Tg-FSH expression restored follicle health, ovulation rates and litter size to wild-type levels. However, Tg-FSH was only able to partially rectify the abnormal oestrous cycles observed in ARKO females. Hence, elevated endogenous FSH rescued the intraovarian defects, and partially rescued the extraovarian defects due to androgen insensitivity. In addition, the observed increase in litter size in Tg-FSH females was not observed in the presence of AR signalling inactivation. In summary, the findings of the present study reveal that FSH can rescue impaired female fertility and ovarian function due to androgen insensitivity in female ARKO mice by maintaining follicle health and ovulation rates, and thereby optimal female fertility.

scholarly journals Erbb4 regulates the oocyte microenvironment during folliculogenesis

2020 ◽  
Vol 29 (17) ◽  
pp. 2813-2830
Author(s):  
Ville Veikkolainen ◽  
Nsrein Ali ◽  
Milena Doroszko ◽  
Antti Kiviniemi ◽  
Ilkka Miinalainen ◽  
...  
Keyword(s):  
Ovarian Function ◽  
Polycystic Ovary ◽  
Association Studies ◽  
Reproductive Function ◽  
Intercellular Junctions ◽  
Ovary Development ◽  
Endocrine Disorders ◽  
Metabolic Systems ◽  
Reproductive Endocrine

Abstract Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders leading to infertility in women affecting reproductive, endocrine and metabolic systems. Recent genomewide association studies on PCOS cohorts revealed a single nucleotide polymorphism (SNP) in the ERBB4 receptor tyrosine kinase 4 gene, but its role in ovary development or during folliculogenesis remains poorly understood. Since no genetic animal models mimicking all PCOS reproductive features are available, we conditionally deleted Erbb4 in murine granulosa cells (GCs) under the control of Amh promoter. While we have demonstrated that Erbb4 deletion displayed aberrant ovarian function by affecting the reproductive function (asynchronous oestrous cycle leading to few ovulations and subfertility) and metabolic function (obesity), their ovaries also present severe structural and functional abnormalities (impaired oocyte development). Hormone analysis revealed an up-regulation of serum luteinizing hormone, hyperandrogenism, increased production of ovarian and circulating anti-Müllerian hormone. Our data implicate that Erbb4 deletion in GCs leads to defective intercellular junctions between the GCs and oocytes, causing changes in the expression of genes regulating the local microenvironment of the follicles. In vitro culture assays reducing the level of Erbb4 via shRNAs confirm that Erbb4 is essential for regulating Amh level. In conclusion, our results indicate a functional role for Erbb4 in the ovary, especially during folliculogenesis and its reduced expression plays an important role in reproductive pathophysiology, such as PCOS development.

scholarly journals Effect of GABA-T on Reproductive Function in Female Rats

Animals ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 567
Author(s):  
Wenyu Si ◽  
Hailing Li ◽  
Tiezhu Kang ◽  
Jing Ye ◽  
Zhiqiu Yao ◽  
...  
Keyword(s):  
Mrna Level ◽  
Reproductive Function ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Lactation Performance ◽  
Irreversible Inhibitor ◽  
Adult Rats ◽  
Expression Of Genes

This study explored the role of γ-aminobutyric acid transaminase (GABA-T) in the puberty and reproductive performance of female rats. Immunofluorescence technique, quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) were used to detect the distribution of GABA-T and the expression of genes and hormones in female rats, respectively. The results showed that GABA-T was mainly distributed in the arcuate nucleus (ARC), paraventricular nucleus (PVN) and periventricular nucleus (PeN) of the hypothalamus, and in the adenohypophysis, ovarian granulosa cells and oocytes. Abat mRNA level at 28 d was lowest in the hypothalamus and the pituitary; at puberty, it was lowest in the ovary. Abat mRNA level was highest in adults in the hypothalamus; at infancy and puberty, it was highest in the pituitary; and at 21 d it was highest in the ovary. After vigabatrin (GABA-T irreversible inhibitor) was added to hypothalamus cells, the levels of Abat mRNA and Rfrp-3 mRNA were significantly reduced, but Gnrh mRNA increased at the dose of 25 and 50 μg/mL; Kiss1 mRNA was significantly increased but Gabbr1 mRNA was reduced at the 50 μg/mL dose. In prepubertal rats injected with vigabatrin, puberty onset was delayed. Abat mRNA, Kiss1 mRNA and Gnrh mRNA levels were significantly reduced, but Rfrp-3 mRNA level increased in the hypothalamus. Vigabatrin reduced the concentrations of GABA-T, luteinizing hormone (LH) and progesterone (P4), and the ovarian index. Lactation performance was reduced in adult rats with vigabatrin treatment. Four hours after vigabatrin injection, the concentrations of GABA-T and LH were significantly reduced in adult and 25 d rats, but follicle-stimulating hormone (FSH) increased in 25 d rats. In conclusion, GABA-T affects the reproductive function of female rats by regulating the levels of Gnrh, Kiss1 and Rfrp-3 in the hypothalamus as well as the concentrations of LH and P4.

Effect of exercise on the onset of puberty, gonadotropins, and ovarian inhibin

1987 ◽  
Vol 63 (3) ◽  
pp. 1165-1173 ◽  
Author(s):  
J. Pellerin-Massicotte ◽  
G. R. Brisson ◽  
C. St-Pierre ◽  
P. Rioux ◽  
D. Rajotte
Keyword(s):  
Luteinizing Hormone ◽  
Exercise Program ◽  
Reproductive Function ◽  
The Body ◽  
Female Rats ◽  
Vaginal Opening ◽  
Adult Rats ◽  
Middle Point ◽  
Critical Weight ◽  
Ovarian Inhibin

Swimming 6 h/day from 11 days of age led to a significant delay of the onset of puberty of female rats compared with the sedentary group. Rats who were in contact with water but without the energy expenditure due to exercise (paddlers) had their vaginal opening in a middle point between control and exercising rats. Vaginal opening occurred at different ages but at a same body weight. Exercise and stress led to a marked decrease of the body weights between 19 and 40 days of age. Serum luteinizing hormone and follicle-stimulating hormone were increased with the exercise program at 30 days of age, whereas no significant differences between groups in serum gonadotropins were observed at 50 days of age. Only the anterior pituitary luteinizing hormone content was increased by exercise in adult rats. Total ovarian proteins were significantly reduced by stress and to a greater degree by exercise. Ovarian inhibin activity is not modified by exercise at 30 days of age, whereas it increased significantly in the exercising group at 50 days of age and to a lesser degree in paddlers. It is therefore suggested that the onset of puberty in rats is dependent on a critical weight and that exercise and stress can delay the onset of puberty. This delay could be explained by a deficiency of hormonal maturational process while exercising until sexual maturity alters the inhibin activity, which suggests that inhibin could play a major role for the normal reproductive function and this could possibly explain the menstrual disturbances in the female athlete.

scholarly journals Impact of hypocaloric dietary intervention on ovulation in obese women with PCOS

Reproduction ◽  
2017 ◽  
Vol 153 (1) ◽  
pp. R15-R27 ◽  
Author(s):  
Brittany Y Jarrett ◽  
Marla E Lujan
Keyword(s):  
Weight Loss ◽  
Dietary Intervention ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Antral Follicle ◽  
Reproductive Age ◽  
Obese Women ◽  
Dietary Interventions ◽  
Wide Range ◽  
The Impact

Polycystic ovary syndrome (PCOS) is a common cause of ovulatory dysfunction affecting women of reproductive age. Obesity and insulin resistance are thought to potentiate disruptions in antral follicle development that result in chronic anovulation, and as such, have become important therapeutic targets of dietary interventions aimed at weight loss. Caloric restriction has been shown to promote sporadic ovulation in obese women with PCOS, but improvements have occurred across a wide range of patients and little has been garnered about the factors that distinguish responders from non-responders. Further, few studies have evaluated the likelihood for modest weight loss to restore normal ovulatory cyclicity in PCOS. Consensus regarding the impact of dietary intervention on ovulation has been limited by variability in the measures used to characterize and report ovulatory status across studies. In response, this review provides an assessment of the evidence surrounding the effectiveness of hypocaloric dietary intervention to normalize ovulatory function in PCOS. The impact of physiological vs methodological factors on the evaluation of ovulatory status is discussed, and recommendations to strengthen future studies in this area are provided. Ultimately, further research is needed to understand the optimal dietary or lifestyle approaches that promote ovulation and sustained improvements in reproductive function in PCOS.

scholarly journals EXPERIMENTAL EVALUATION OF LONG-TERM ADVERSE SIDE EFFECTS OF CYTOSTATIC DRUGS ON FEMALE REPRODUCTIVE FUNCTION AND PHARMACOLOGICAL WAYS TO REDUCE THEM

2021 ◽  
Vol 20 (1) ◽  
pp. 87-96
Author(s):  
T. G. Borovskaya ◽  
V. E. Goldberg ◽  
M. E. Poluektova ◽  
A. V. Vychuzhanina ◽  
Yu. A. Shchemerovа ◽  
...  
Keyword(s):  
Ovarian Reserve ◽  
Structural Damage ◽  
Reproductive Potential ◽  
Reproductive Function ◽  
Female Rats ◽  
Male Rats ◽  
Fetal Mortality ◽  
Cytostatic Drugs ◽  
Adult Rats

The purpose of the study was a comparative experimental assessment of long-term toxic effects of cytostatic drugs (epirubicin, etoposide, platidiam, carboplatin, paclitaxel) on the female reproductive function and search for pharmacological ways to reduce them.Material and Methods. Experiments were carried out on 200 outbred male rats, Wistar stock, 2.5 months old. Antitumor drugs were administered once, intravenously, in maximum tolerated dose. The reproductive status in rats was assessed 90 and 180 days after injection of cytostatic drugs. Correction of ovariotoxicity of cytostatic drugs was carried out using a recombinant human granulocyte colony stimulating factor (rhG-CS F, Neupomax, FARMSTA NDA RT-UfaVITA OJSC , Russia) and liquid extract of Scutellaria Baikalsky («GNTsLS », Kharkov). The mating and fertility ability of female rats as well as pre- and post-implantation fetal mortality were determined. Ovarian reserve was evaluated using morphological analysis of the ovaries using quantitative assessments of structural damage. Concentration of anti-Muller hormone in the blood of adult rats-females receiving etoposide and rhG-CS F were evaluated by enzyme immunoassay (IFA, ELISA , Cloud clone, Corp. Wuhan). Statistical processing of obtained experimental data was performed using Mann-Whitney U-test and Fisher angular transformation.Results. The mating and fertility ability of animals was found to be persisted. However, signs of early depletion of the ovarian reserve and a decrease in reproductive potential were observed. The risk of early menopause was increased to a greater extent after using epirubicin, etoposide and paclitaxel, and to a lesser extent after platidiam and carboplatin. The reproductive potential of animals was reduced due to increased fetal death. Platinum-containing drugs were found to be the most toxic. G-CS F was the effective drug for protecting the ovarian reserve from cytostatic effects. The use of Scutellaria baicalensis extract increased the reproductive potential of animals by reducing the rate of embryonic death. 

scholarly journals Obesity induced by high-fat diet promotes insulin resistance in the ovary

2010 ◽  
Vol 206 (1) ◽  
pp. 65-74 ◽  
Author(s):  
Eliana H Akamine ◽  
Anderson C Marçal ◽  
João Paulo Camporez ◽  
Mara S Hoshida ◽  
Luciana C Caperuto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Insulin Signaling Pathway ◽  
Female Rats ◽  
High Fat ◽  
Obese Rats

Besides the effects on peripheral energy homeostasis, insulin also has an important role in ovarian function. Obesity has a negative effect on fertility, and may play a role in the development of the polycystic ovary syndrome in susceptible women. Since insulin resistance in the ovary could contribute to the impairment of reproductive function in obese women, we evaluated insulin signaling in the ovary of high-fat diet-induced obese rats. Female Wistar rats were submitted to a high-fat diet for 120 or 180 days, and the insulin signaling pathway in the ovary was evaluated by immunoprecipitation and immunoblotting. At the end of the diet period, we observed insulin resistance, hyperinsulinemia, an increase in progesterone serum levels, an extended estrus cycle, and altered ovarian morphology in obese female rats. Moreover, in female obese rats treated for 120 days with the high-fat diet, the increase in progesterone levels occurred together with enhancement of LH levels. The ovary from high-fat-fed female rats showed a reduction in the insulin receptor substrate/phosphatidylinositol 3-kinase/AKT intracellular pathway, associated with an increase in FOXO3a, IL1B, and TNFα protein expression. These changes in the insulin signaling pathway may have a role in the infertile state associated with obesity.

Faecal corticosterone and immunoglobulin A in young adult rats

2003 ◽  
Vol 37 (2) ◽  
pp. 166-171 ◽  
Author(s):  
Liselotte Pihl ◽  
Jann Hau
Keyword(s):  
Body Weight ◽  
Young Adult ◽  
Time Windows ◽  
Immunoglobulin A ◽  
Time Of Day ◽  
Female Rats ◽  
Male Rats ◽  
Adult Rats ◽  
Faecal Pellets ◽  
Non Invasive

Quantitative analyses of relevant molecules in faeces may have potential as future non-invasive measures of stress. This study examined levels of faecal corticosterone and immunoglobulin A (IgA) in young adult rats and how these levels varied according to age, gender and time of day. Faecal samples were collected from 40 young adult rats (7 weeks old, n = 20 and 10 weeks old, n = 20) of both sexes from two time windows: day and night. The concentrations of corticosterone and IgA were measured by ELISAs following organic solvent extraction and aqueous extraction, respectively, of the molecules from faecal pellets. The production of faeces per time unit was higher in males than in females, and linear correlations were found between the faecal concentrations of corticosterone and IgA and total amounts of the respective molecules excreted in faeces per kg body weight per hour. In all further analyses the levels of the two molecules were calculated as amounts secreted per kg of body weight per hour. There was no gender difference between females and males in the production of corticosterone and IgA, but 7-week-old animals excreted significantly higher amounts of both molecules than did 10-week-old rats. The levels of IgA excreted by female rats were higher in the evening than in the morning, and male rats excreted higher concentrations of corticosterone in the morning than in the evening.

scholarly journals Androgens and ovarian function: translation from basic discovery research to clinical impact

2019 ◽  
Vol 242 (2) ◽  
pp. R23-R50 ◽  
Author(s):  
K A Walters ◽  
V Rodriguez Paris ◽  
A Aflatounian ◽  
D J Handelsman
Keyword(s):  
Future Development ◽  
Molecular Mechanisms ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Reproductive Function ◽  
Poor Responders ◽  
Discovery Research ◽  
The Future ◽  
The Impact

In the last decade, it has been revealed that androgens play a direct and important role in regulating female reproductive function. Androgens mediate their actions via the androgen receptor (AR), and global and cell-specific Ar-knockout mouse models have confirmed that AR-mediated androgen actions play a role in regulating female fertility and follicle health, development and ovulation. This knowledge, along with the clinical data reporting a beneficial effect of androgens or androgen-modulating agents in augmenting in vitro fertilization (IVF) stimulation in women termed poor responders, has supported the adoption of this concept in many IVF clinics worldwide. On the other hand, substantial evidence from human and animal studies now supports the hypothesis that androgens in excess, acting via the AR, play a key role in the origins of polycystic ovary syndrome (PCOS). The identification of the target sites of these AR actions and the molecular mechanisms involved in underpinning the development of PCOS is essential to provide the knowledge required for the future development of novel, mechanism-based therapies for the treatment of PCOS. This review will summarize the basic scientific discoveries that have enhanced our knowledge of the roles of androgens in female reproductive function, discuss the impact these findings have had in the clinic and how a greater understanding of the role androgens play in female physiology may shape the future development of effective strategies to improve IVF outcomes in poor responders and the amelioration of symptoms in patients with PCOS.

scholarly journals Neonatal programming by immunological challenge: effects on ovarian function in the adult rat

Reproduction ◽  
2011 ◽  
Vol 141 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Xue-Qing Wu ◽  
Xiao-Feng Li ◽  
Bilu Ye ◽  
Neha Popat ◽  
Stuart R Milligan ◽  
...  
Keyword(s):  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ovarian Function ◽  
Pulse Generator ◽  
Female Rats ◽  
Neonatal Exposure ◽  
Inhibitory Influence ◽  
Nerve Activity ◽  
Adult Rats ◽  
Theca Interna

Neonatal exposure to an immunological challenge (lipopolysaccharide, LPS) increases the activity of hypothalamo-pituitary–adrenal axis and sensitises the GNRH pulse generator to the inhibitory influence of stress in adult rats. We investigated the effects of neonatal exposure to LPS on various reproductive parameters during puberty and into adulthood in female rats. LPS (50 μg/kg, i.p.) or saline was administered on postnatal days 3 and 5. Vaginal opening was recorded, and oestrous cyclicity was monitored immediately post puberty and again at 8–9 weeks of age. At 10 weeks of age, the ovaries were removed and the number of follicles was counted, together with the thickness of the theca interna of the largest antral follicles. Ovarian sympathetic nerve activity was assessed immunohistochemically by measurement of the levels of ovarian low-affinity receptor of nerve growth factor (p75NGFR). In rats exposed to LPS in early life, there was a significant delay in puberty and disruption of oestrous cyclicity immediately post puberty, which persisted into adulthood. The follicle reserve was decreased, the thickness of the theca interna increased and the expression profile of ovarian p75NGFR increased in the neonatal LPS-treated animals. These data suggest that exposure to LPS during early neonatal life can have long-term dysfunctional effects on the female reproductive system, which might involve, at least in part, increased ovarian sympathetic nerve activity.

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