scholarly journals Activation of Norepinephrine Neurons in the NTS (A2 population) is Sufficient to Suppress Pulsatile LH Secretion in Female Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A531-A531
Author(s):  
Richard B McCosh ◽  
Michael J Kreisman ◽  
Katherine Tian ◽  
Steven A Thomas ◽  
Kellie M Breen
Keyword(s):  
Acute Stress ◽  
Cell Activity ◽  
Metabolic Stress ◽  
Pulse Frequency ◽  
Designer Drugs ◽  
Transduction Efficiency ◽  
Neural Pathways ◽  
Wild Type ◽  
Female Mice ◽  
Lh Secretion

Abstract The overarching goal of this work is to identify neural pathways underlying inhibition of pulsatile luteinizing hormone (LH) secretion during stress. Stress-induced suppression of LH secretion is mediated, at least in part, by suppression of arcuate kisspeptin (ARCKiss1) neurons. The mechanisms by which acute stress suppresses ARCKiss1 cell activity are largely unknown; however, several lines of evidence support the hypothesis that A2 neurons (norepinephrine [NE] neurons in the nucleus of the solitary tract [NTS] of the brainstem) are involved. First, A2 cells are activated during several reactive stress paradigms. Second, NE administered into the paraventricular nucleus, which is innervated by A2 neurons, suppressed pulsatile LH secretion. Finally, ablation of brainstem NE neurons restored estrous cyclicity following chronic glucoprivation (chronic metabolic stress model). The present study employed chemogenetics to test the hypothesis that A2 neurons are sufficient to suppress pulsatile LH secretion in ovariectomized female dopamine beta-hydroxylase (DBH) Cre positive and negative (wild type) mice. Mice received bilateral injections of either a Cre-dependent stimulatory Designer Receptor Exclusively Activated by Designer Drugs (DREADD) virus (AAV1-DIO-hM3Dq-mCherry) or a control virus (AAV1-DIO-mCherry) into the NTS. Mice were randomly assigned to receive either clozapine N-oxide (CNO, specific DREADD agonist; 1mg/kg, i.p.) or saline and blood samples were collected at 6-min intervals for 60 min before and 90 min after injection. Two weeks later, mice received the alternate treatment in a cross-over design (n= 5-10/grp). During the pre-injection period, all mice had clear LH pulses (mean: 6.0 ± 0.2 ng/mL, pulses/60 min: 3.4 ± 1.5). In DBH Cre- (wild type) mice with hM3D virus and DBH Cre+ with mCherry virus (both control groups), neither CNO nor saline altered mean LH or LH pulse frequency. However, DBH Cre+ mice with hM3D virus had a 54% reduction in mean LH (p < 0.05) and 59% reduction in pulse frequency (p < 0.05) following CNO; neither LH metric was altered in response to saline. To assess transduction efficiency, fixed neural tissue was collected. In tissue analyzed thus far, DBH Cre+ mice have mCherry labeling in ~70% of DBH-immunoreactive neurons in the NTS and >90% of mCherry neurons contained DBH immunoreactivity. Three DBH Cre+ mice with hM3D virus mice had no LH response to CNO and may represent missed viral injections, which will be determined when tissue is analyzed. These data demonstrate that activation of A2 neurons is sufficient to impair pulsatile LH secretion in female mice. Moreover, these data support the broad hypothesis that the A2 population of neurons is critical for modulating neuroendocrine function during stress and raises the possibility that A2 neurons directly or indirectly influence ARCKiss1 cell activity.

scholarly journals Androgen Suppresses In Vivo and In Vitro LH Pulse Secretion and Neural Kiss1 and Tac2 Gene Expression in Female Mice

Endocrinology ◽  
2020 ◽  
Vol 161 (12) ◽  
Author(s):  
Lourdes A Esparza ◽  
Tomohiro Terasaka ◽  
Mark A Lawson ◽  
Alexander S Kauffman
Keyword(s):  
Gene Expression ◽  
Pulse Frequency ◽  
Normal Male ◽  
Steroid Abuse ◽  
Female Mice ◽  
Reproductive Axis ◽  
Lh Pulsatility ◽  
Lh Secretion

Abstract Androgens can affect the reproductive axis of both sexes. In healthy women, as in men, elevated exogenous androgens decrease gonad function and lower gonadotropin levels; such circumstances occur with anabolic steroid abuse or in transgender men (genetic XX individuals) taking androgen supplements. The neuroendocrine mechanisms by which endogenous or exogenous androgens regulate gonadotropin release, including aspects of pulsatile luteinizing hormone (LH) secretion, remain unknown. Because animal models are valuable for interrogating neural and pituitary mechanisms, we studied effects of androgens in the normal male physiological range on in vivo LH secretion parameters in female mice and in vitro LH secretion patterns from isolated female pituitaries. We also assessed androgen effects on hypothalamic and gonadotrope gene expression in female mice, which may contribute to altered LH secretion profiles. We used a nonaromatizable androgen, dihydrotestosterone (DHT), to isolate effects occurring specifically via androgen receptor (AR) signaling. Compared with control females, DHT-treated females exhibited markedly reduced in vivo LH pulsatility, with decreases in pulse frequency, amplitude, peak, and basal LH levels. Correlating with reduced LH pulsatility, DHT-treated females also exhibited suppressed arcuate nucleus Kiss1 and Tac2 expression. Separate from these neural effects, we determined in vitro that the female pituitary is directly inhibited by AR signaling, resulting in lower basal LH levels and reduced LH secretory responses to gonadotropin-releasing hormone pulses, along with lower gonadotropin gene expression. Thus, in normal adult females, male levels of androgen acting via AR can strongly inhibit the reproductive axis at both the neural and pituitary levels.

scholarly journals SUN-257 Evidence that Urocortin 2 Contributes to the Suppressive Effect of Metabolic Stress on LH Secretion in Female Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Richard B McCosh ◽  
Michael J Kreisman ◽  
Katherine Tian ◽  
Kellie M Breen
Keyword(s):  
Cell Function ◽  
Acute Stress ◽  
Metabolic Stress ◽  
Suppressive Effect ◽  
Mrna Abundance ◽  
Neurokinin B ◽  
Blood Samples ◽  
Expression Of Genes ◽  
Lh Secretion ◽  
Lines Of Evidence

Abstract Pulsatile luteinizing hormone (LH) secretion is disrupted by numerous stimuli including metabolic stress. Insulin-induced hypoglycemia is a model of metabolic stress that suppresses LH secretion in numerous species including mice. Our recent work provides evidence that this inhibition of LH secretion occurs via suppression of neurons that contain kisspeptin (Kiss1), neurokinin B (NKB) and dynorphin (Dyn) in the arcuate (ARC) nucleus (KNDy cells). Thus, our current objective is to identify the neural components responsible for the suppression of KNDy cells during metabolic stress. Several lines of evidence support the hypothesis that the neuropeptide urocortin 2 (UCN2) has a key role in the inhibition of LH during stress in rats. First, ICV injection of UCN2 suppresses LH secretion. Second, an antagonist to the receptor for UCN2 reverses the suppression of LH during metabolic stress. Finally, restraint and osmotic stress increase UCN2 mRNA abundance in the paraventricular nucleus (PVN). To determine if UCN2 neurons in the PVN are activated during metabolic stress we performed immunohistochemistry for UCN2 and c-Fos in tissue collected 120 min after saline or insulin (0.75mU/kg) injection (n = 2/group, ovariectomized, adult, C57/BL6). Insulin significantly increased both the number of UCN2 cells (saline: 109.0 ± 8.5, insulin: 156.3 ± 10.8 cells) and the percentage of UCN2 cells that expressed c-Fos (saline: 13.1 ± 2.5%, insulin: 31.2 ± 0.8%). Next, we administered UCN2 (7.23nmol) via ICV injection to determine if this molecule suppresses LH secretion and/or mRNA abundance of KNDy genes. LH was measured in serial blood samples collected from 60 min prior to and 30-90 min following injection. Tissue was collected 3 h after ICV injection to confirm injection site and quantify mRNA abundance in ARC micropunches. In saline-treated mice (n = 5 successful injections), mean LH concentration and the number of LH pulses did not differ across sampling periods (mean: 6.4 ± 0.4 ng/mL vs. 6.0 ± 0.4 ng/mL; pulses: 2.6 ± 0.2 vs. 3.0 ± 0.3, pre vs. post). In contrast, in mice with successful UCN2 injections (n = 4) there was a significant reduction in both mean LH and the number of LH pulses following UCN2 (mean: 5.0 ± 0.3 ng/mL vs. 1.4 ± 0.2 ng/mL; pulses: 3.0 ± 0.0 vs. 0.25 ± 0.25, pre vs post). UCN2-treated animals had a significant reduction in the abundance of mRNAs encoding Kiss1 (~35%) and NKB (~40%) compared to saline-treated animals; the abundance of Dyn mRNA did not differ between treatments. These data demonstrate that PVN UCN2 cells are activated during metabolic stress and that UCN2 is sufficient to suppress LH secretion and the expression of genes involved in stimulating LH pulses. These data support the hypothesis that UCN2 released from neurons in the PVN impairs KNDy cell function and LH secretion during acute stress.

scholarly journals Estradiol Enables Chronic Corticosterone to Inhibit Pulsatile Luteinizing Hormone Secretion and Suppress Kiss1 Neuronal Activation in Female Mice

2019 ◽  
Vol 110 (6) ◽  
pp. 501-516 ◽  
Author(s):  
Michael J. Kreisman ◽  
Richard B. McCosh ◽  
Katherine Tian ◽  
Christopher I. Song ◽  
Kellie M. Breen
Keyword(s):  
Luteinizing Hormone ◽  
Hormone Secretion ◽  
Pulse Frequency ◽  
Dependent Manner ◽  
Neuronal Activation ◽  
Luteinizing Hormone Secretion ◽  
Female Mice ◽  
Enhanced Sensitivity ◽  
Ovarian Cyclicity ◽  
Lh Secretion

Introduction: Two common responses to stress include elevated circulating glucocorticoids and impaired luteinizing hormone (LH) secretion. We have previously shown that a chronic stress level of corticosterone can impair ovarian cyclicity in intact mice by preventing follicular-phase endocrine events. Objective: This study is aimed at investigating if corticosterone can disrupt LH pulses and whether estradiol is necessary for this inhibition. Methods: Our approach was to measure LH pulses prior to and following the administration of chronic corticosterone or cholesterol in ovariectomized (OVX) mice treated with or without estradiol, as well as assess changes in arcuate kisspeptin (Kiss1) neuronal activation, as determined by co-expression with c-Fos. Results: In OVX mice, a chronic 48 h elevation in corticosterone did not alter the pulsatile pattern of LH. In contrast, corticosterone induced a robust suppression of pulsatile LH secretion in mice treated with estradiol. This suppression represented a decrease in pulse frequency without a change in amplitude. We show that the majority of arcuate Kiss1 neurons contain glucocorticoid receptor, revealing a potential site of corticosterone action. Although arcuate Kiss1 and Tac2 gene expression did not change in response to corticosterone, arcuate Kiss1 neuronal activation was significantly reduced by chronic corticosterone, but only in mice treated with estradiol. Conclusions: Collectively, these data demonstrate that chronic corticosterone inhibits LH pulse frequency and reduces Kiss1 neuronal activation in female mice, both in an estradiol-dependent manner. Our findings support the possibility that enhanced sensitivity to glucocorticoids, due to ovarian steroid milieu, may contribute to reproductive impairment associated with stress or pathophysiologic conditions of elevated glucocorticoids.

scholarly journals Seasonal and dose-dependent effects of intracerebroventricular leptin on lh secretion and appetite in sheep

2002 ◽  
Vol 175 (2) ◽  
pp. 395-404 ◽  
Author(s):  
DW Miller ◽  
PA Findlay ◽  
MA Morrison ◽  
N Raver ◽  
CL Adam
Keyword(s):  
Moving Average ◽  
Third Ventricle ◽  
Pulse Amplitude ◽  
Pulse Frequency ◽  
Saline Control ◽  
Neural Pathways ◽  
Post Injection ◽  
Reproductive Regulation ◽  
Lh Secretion ◽  
Dose Dependent

The role of leptin in neuroendocrine appetite and reproductive regulation remains to be fully resolved. A series of three experiments was conducted using adequately nourished oestradiol-implanted castrated male sheep. In a cross-over design (n=6), responses to a single i.c.v. (third ventricle) injection of leptin (0.5, 1.0 and 1.5 mg ovine leptin (oLEP) and 1.0 mg murine leptin (mLEP)), N-methyl-D-aspartate (NMDA, 20 micro g) or 0.9% saline (control) were measured in terms of LH secretion (4 h post-injection compared with 4 h pre-injection) and appetite (during 2 h post-injection) in autumn (Experiment 1). NMDA and 1.0 mg oLEP treatments were repeated in the same sheep in the following spring (Experiment 2). With an additional 12 sheep (n=18 in cross-over design), responses to low-dose 'physiological' i.c.v. infusion of leptin (8 ng/h for 12 h daily for 4 days), insulin (0.7 ng/h) and artificial cerebrospinal fluid were measured in the next spring (Experiment 3). LH was studied over 8 h and appetite over 1 h on days 1 and 4 of infusion. In Experiment 1 (autumn), oLEP overall increased LH pulse frequency by up to 110% (P<0.05), decreased LH pulse amplitude (P<0.05) and decreased appetite (P<0.05). mLEP reduced LH pulse amplitude (P<0.05) without significant effect on appetite, while NMDA reduced appetite (P<0.05) but had no effect on LH. In Experiment 2 (spring), LH responses were 'surge-like' with highly significant increases in the moving average LH concentration after 1.0 mg oLEP (P<0.001) and after NMDA (P<0.001). Compared with similar analysis of experiment 1 results, the LH response in spring was greater than that in autumn for both 1.0 mg oLEP (P<0.05) and NMDA (P<0.005). Conversely, unlike in autumn (Experiment 1), there was no effect of 1.0 mg oLEP or NMDA on appetite in the spring (Experiment 2). In Experiment 3 (spring), 'physiological' i.c.v. infusion of oLEP or insulin increased LH pulse frequency by up to 100% (P<0.001) compared with the control infusion on both days 1 and 4, but there were no effects on appetite. These results indicate that intracerebral leptin both stimulates reproductive neuroendocrine output and decreases appetite in adequately nourished sheep. However, the responses of these two axes were dose-dependent and differentially affected by the time of year, suggesting dissociation of the neural pathways involved.

scholarly journals Kisspeptin Stimulates the Pulsatile Secretion of Luteinizing Hormone (LH) during Postpartum Anestrus in Ewes Undergoing Continuous and Restricted Suckling

Animals ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 2656
Author(s):  
José Manuel Hernández-Hernández ◽  
Graeme B. Martin ◽  
Carlos Miguel Becerril-Pérez ◽  
Arturo Pro-Martínez ◽  
César Cortez-Romero ◽  
...  
Keyword(s):  
Luteinizing Hormone ◽  
Jugular Vein ◽  
Pulse Frequency ◽  
Neural Pathways ◽  
Indwelling Catheter ◽  
Pulsatile Secretion ◽  
Intravenous Application ◽  
Access To Water ◽  
Ad Libitum ◽  
Lh Secretion

This study tested whether the intravenous application of kisspeptin can stimulate the pulsatile secretion of LH in suckling ewes during postpartum anestrus. Ten days after lambing, Pelibuey ewes were allocated among two groups: (1) continuous suckling (n = 8), where the lambs remained with their mothers; and (2) restricted suckling (n = 8), where the mothers suckled their lambs twice daily for 30 min. On Day 19 postpartum, the ewes were individually penned with ad libitum access to water and feed and given an indwelling catheter in each jugular vein. On Day 20, 4 mL of blood was sampled every 15 min from 08:00 to 20:00 h to determine LH pulse frequency. At 14:00 h, four ewes in each group received 120 μg of kisspeptin diluted in 3 mL of saline as a continuous infusion for 6 h; the remaining four ewes in each group received only saline. The interaction between kisspeptin and suckling type did not affect LH pulse frequency (p > 0.05). Before kisspeptin administration, pulse frequency was similar in all groups (1.50 ± 0.40 pulses per 6 h; p > 0.05). With the application of kisspeptin, pulse frequency increased to 3.50 ± 0.43 pulses per 6 h (p ≤ 0.014), so the concentration of LH (1.11 ± 0.14 ng mL−1) was greater in kisspeptin-treated ewes than in saline-treated ewes (0.724 ± 0.07 ng mL−1; p ≤ 0.040). The frequency of LH pulses was greater with restricted suckling than with continuous suckling (2.44 ± 0.29 versus 1.69 ± 0.29 pulses per 6 h; p ≤ 0.040). We conclude that intravenous application of kisspeptin increases the pulsatile secretion of LH in suckling ewes and that suckling might reduce kisspeptin neuronal activity, perhaps explaining the suppression of ovulation. Moreover, the effects of kisspeptin and suckling on pulsatile LH secretion appear to be independent, perhaps operating through different neural pathways.

Effects of acute stress on the patterns of LH secretion in the common marmoset (Callithrix jacchus)

1988 ◽  
Vol 118 (2) ◽  
pp. 259-264 ◽  
Author(s):  
K. T. O'Byrne ◽  
S. F. Lunn ◽  
A. F. Dixson
Keyword(s):  
Acute Stress ◽  
Mammalian Species ◽  
Physical Restraint ◽  
Plasma Concentrations ◽  
Social Rank ◽  
Pulse Amplitude ◽  
Common Marmoset ◽  
Pulse Frequency ◽  
Lh Releasing Hormone ◽  
Lh Secretion

ABSTRACT Stressful stimuli associated with aggressive encounters and low social rank may affect female fertility in a variety of mammalian species. In these experiments we examined the effects of aggressive encounters and physical restraint in a primate chair on the patterns of LH secretion in ovariectomized, oestrogen-primed female marmosets. Receipt of aggression from a female conspecific, followed by physical restraint for collection of blood samples (at 10-min intervals for 4 h), resulted in marked declines in LH concentrations during oestradiol-induced LH surges in five animals (from 112 ± 24 μg/l to 45±12 μg/l; group means ± s.e.m.; P<0·05). This was due to reductions in LH pulse amplitude rather than to changes in pulse frequency. Decreases in plasma concentrations of LH were reversed by treating females with exogenous LH-releasing hormone (LHRH). Cortisol treatment had no effect on LH levels during oestrogen-induced LH surges. Effects of aggressive encounters and physical restraint on plasma LH were not therefore due to reduced pituitary responsiveness to LHRH or to increased plasma concentrations of cortisol. In separate experiments it was found that physical restraint alone had no effect on plasma LH in habituated subjects, and that decreases in plasma LH after receipt of aggression only occurred if animals were subsequently placed in the restraint chair. A summation of stressful effects is therefore required to produce the fall in circulating LH. A summation of social and other environmental stressors may also underlie the reduced fertility seen in free-living animals. J. Endocr. (1988) 118, 259–264

scholarly journals Chronic High Fat Diet Intake Impairs Hepatic Metabolic Parameters in Ovariectomized Sirt3 KO Mice

2021 ◽  
Vol 22 (8) ◽  
pp. 4277
Author(s):  
Marija Pinterić ◽  
Iva I. Podgorski ◽  
Marijana Popović Hadžija ◽  
Ivana Tartaro Bujak ◽  
Ana Tadijan ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Lipid Hydroperoxide ◽  
Metabolic Stress ◽  
Lipid Hydroperoxides ◽  
Ros Scavenging ◽  
High Fat ◽  
Preclinical Research ◽  
Female Mice

High fat diet (HFD) is an important factor in the development of metabolic diseases, with liver as metabolic center being highly exposed to its influence. However, the effect of HFD-induced metabolic stress with respect to ovary hormone depletion and sirtuin 3 (Sirt3) is not clear. Here we investigated the effect of Sirt3 in liver of ovariectomized and sham female mice upon 10 weeks of feeding with standard-fat diet (SFD) or HFD. Liver was examined by Folch, gas chromatography and lipid hydroperoxide analysis, histology and oil red staining, RT-PCR, Western blot, antioxidative enzyme and oxygen consumption analyses. In SFD-fed WT mice, ovariectomy increased Sirt3 and fatty acids synthesis, maintained mitochondrial function, and decreased levels of lipid hydroperoxides. Combination of ovariectomy and Sirt3 depletion reduced pparα, Scd-1 ratio, MUFA proportions, CII-driven respiration, and increased lipid damage. HFD compromised CII-driven respiration and activated peroxisomal ROS scavenging enzyme catalase in sham mice, whereas in combination with ovariectomy and Sirt3 depletion, increased body weight gain, expression of NAFLD- and oxidative stress-inducing genes, and impaired response of antioxidative system. Overall, this study provides evidence that protection against harmful effects of HFD in female mice is attributed to the combined effect of female sex hormones and Sirt3, thus contributing to preclinical research on possible sex-related therapeutic agents for metabolic syndrome and associated diseases.

scholarly journals Carcinoembryonic antigen cell adhesion molecule 6 (CEACAM6) in Pancreatic Ductal Adenocarcinoma (PDA): An integrative analysis of a novel therapeutic target

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ritu Pandey ◽  
Muhan Zhou ◽  
Shariful Islam ◽  
Baowei Chen ◽  
Natalie K Barker ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Pancreatic Ductal Adenocarcinoma ◽  
Therapeutic Target ◽  
Cell Activity ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Ductal Adenocarcinoma ◽  
Wild Type ◽  
Cancer Genome Atlas ◽  
Novel Therapeutic

AbstractWe investigated biomarker CEACAM6, a highly abundant cell surface adhesion receptor that modulates the extracellular matrix (ECM) in pancreatic ductal adenocarcinoma (PDA). The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) RNA-Seq data from PDA patients were analyzed for CEACAM6 expression and evaluated for overall survival, association, enrichment and correlations. A CRISPR/Cas9 Knockout (KO) of CEACAM6 in PDA cell line for quantitative proteomics, mitochondrial bioenergetics and tumor growth in mice were conducted. We found CEACAM6 is over-expressed in primary and metastatic basal and classical PDA subtypes. Highest levels are in classical activated stroma subtype. CEACAM6 over-expression is universally a poor prognostic marker in KRAS mutant and wild type PDA. High CEACAM6 expression is associated with low cytolytic T-cell activity in both basal and classical PDA subtypes and correlates with low levels of T-REG markers. In HPAF-II cells knockout of CEACAM6 alters ECM-cell adhesion, catabolism, immune environment, transmembrane transport and autophagy. CEACAM6 loss increases mitochondrial basal and maximal respiratory capacity. HPAF-II CEACAM6−/− cells are growth suppressed by >65% vs. wild type in mice bearing tumors. CEACAM6, a key regulator affects several hallmarks of PDA including the fibrotic reaction, immune regulation, energy metabolism and is a novel therapeutic target in PDA.

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.

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