Estradiol-Induced Senescence of Hypothalamic Astrocytes Contributes to Aging-Related Reproductive Function Declines in Female Mice

2019 ◽  
Author(s):  
Xiaoman Dai ◽  
Luyan Hong ◽  
Hui Shen ◽  
Qiang Du ◽  
Qinyong Ye ◽  
...  
2004 ◽  
Vol 183 (1) ◽  
pp. 29-38 ◽  
Author(s):  
Mika Suzuki ◽  
Hiroshi Kobayashi ◽  
Yoshiko Tanaka ◽  
Naohiro Kanayama ◽  
Toshihiko Terao

Bikunin, a Kunitz-type protease inhibitor, is found in blood and urine. It has been established by two laboratories independently that the bikunin knockout female mice display a severe reduction in fertility: the cumulus oophorus has a defect in forming the extracellular hyaluronan-rich matrix during expansion. Proteins of the inter-alpha-trypsin inhibitor (ITI) family are eliminated in mice in which the bikunin gene has been inactivated, since bikunin is essential for their biosynthesis. Proteins of the ITI family may contribute to the microenvironment in which ovulation takes place. It is not clear, however, whether a single mechanism affects the reproductive function including ovulation. For identifying the full repertoire of the ITI deficiency-related genes, a cDNA microarray hybridization screening was conducted using mRNA from ovaries of wild-type or bik−/− female mice. A number of genes were identified and their regulation was confirmed by real-time RT-PCR analysis. Our screen identified that 29 (0.7%) and 5 genes (0.1%) of the genes assayed were, respectively, up- and down-regulated twofold or more. The identified genes can be classified into distinct subsets. These include stress-related, apoptosis-related, proteases, signaling molecules, aging-related, cytokines, hyaluronan metabolism and signaling, reactive oxygen species-related, and retinoid metabolism, which have previously been implicated in enhancing follicle development and/or ovulation. Real-time RT-PCR analysis confirmed that these genes were up- and down-regulated two- to tenfold by bikunin knockout. These studies demonstrate that proteins of the ITI family may exert potent regulatory effects on a major physiological reproductive process, ovulation.


2017 ◽  
Vol 29 (7) ◽  
pp. 1426 ◽  
Author(s):  
K. A. Walters ◽  
M. C. Edwards ◽  
M. Jimenez ◽  
D. J. Handelsman ◽  
C. M. Allan

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.


2017 ◽  
Vol 29 (5) ◽  
pp. 1012 ◽  
Author(s):  
Rahmatollah Parandin ◽  
Morteza Behnam-Rassouli ◽  
Nasser Mahdavi-Shahri

Tamoxifen, a selective oestrogen receptor modulator, is widely used for both the treatment and prevention of breast cancer in women; however, it is known to have adverse effects in the female reproductive system. Growing evidence suggests that oestrogen-sensitive neuron populations of the anteroventral periventricular (AVPV) nucleus and arcuate (ARC) nucleus, especially kisspeptin neurons, play a pivotal role in the timing of puberty onset and reproductive function. The aim of the present study was to evaluate whether neonatal exposure to tamoxifen affects oestrogenic actions in the brain and reproductive function in mice. On 1 to 5 postnatal days, female pups were injected subcutaneously with sesame oil (sham), oestradiol benzoate (EB; 20 µg kg–1), tamoxifen (0.4 mg kg–1) or EB+tamoxifen. Control mice received no treatment. Mice in the EB, tamoxifen and tamoxifen+EB groups exhibited advanced vaginal opening, disrupted oestrous cycles and a decreased follicular pool. Conversely, in these groups, there was a reduction in kisspeptin (Kiss1) mRNA expression, the neuronal density of AVPV and ARC nuclei and LH and oestradiol concentrations in the serum. The results of the present study confirm oestrogenic actions of tamoxifen in the brain and reproductive system. In addition, we show, for the first time, that tamoxifen has oestrogenic effects on the oestrogen-sensitive hypothalamic AVPV and ARC nuclei controlling the reproductive axis in female mice.


2014 ◽  
Vol 2014 (1) ◽  
pp. 2137
Author(s):  
Jian Zhou* ◽  
Honghui Li ◽  
Lingqin Zhu ◽  
Huifang Yang ◽  
Yanhong Cui ◽  
...  

2006 ◽  
Vol 87 (2) ◽  
pp. 416-423 ◽  
Author(s):  
Zeynep Benderlioglu ◽  
Jenny Eish ◽  
Zachary M. Weil ◽  
Randy J. Nelson

Nitric Oxide ◽  
1999 ◽  
Vol 3 (5) ◽  
pp. 366-374 ◽  
Author(s):  
Deborah L. Drazen ◽  
Sabra L. Klein ◽  
Arthur L. Burnett ◽  
Edward E. Wallach ◽  
Julie K. Crone ◽  
...  

2016 ◽  
Vol 106 (3) ◽  
pp. e119
Author(s):  
K. Lee ◽  
J. Joo ◽  
S. Kim ◽  
S. Lee

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