Evaluation of Neonatal Exposure to Mycoestrogens Zearalenone  and Alpha-zearalenol on Puberty and Reproductive  Function in Female Mice

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.

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

Reproduction Fertility and Development ◽

10.1071/rd16022 ◽

2017 ◽

Vol 29 (7) ◽

pp. 1426 ◽

Cited By ~ 2

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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Oestrogenic action of neonatal tamoxifen on the hypothalamus and reproductive system in female mice

Reproduction Fertility and Development ◽

10.1071/rd15361 ◽

2017 ◽

Vol 29 (5) ◽

pp. 1012 ◽

Cited By ~ 2

Author(s):

Rahmatollah Parandin ◽

Morteza Behnam-Rassouli ◽

Nasser Mahdavi-Shahri

Keyword(s):

Reproductive System ◽

Reproductive Function ◽

Female Mice ◽

Treatment And Prevention ◽

Receptor Modulator ◽

Neuron Populations ◽

Reproductive Axis ◽

First Time ◽

The Brain ◽

Selective Oestrogen Receptor Modulator

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.

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The Impact of Sodium Fluoride on Reproductive Function of Female Mice and Behavior of the Offspring

ISEE Conference Abstracts ◽

10.1289/isee.2014.p2-531 ◽

2014 ◽

Vol 2014 (1) ◽

pp. 2137

Author(s):

Jian Zhou* ◽

Honghui Li ◽

Lingqin Zhu ◽

Huifang Yang ◽

Yanhong Cui ◽

...

Keyword(s):

Sodium Fluoride ◽

Reproductive Function ◽

Female Mice ◽

And Behavior ◽

The Impact

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Effects of Neonatal Exposure to Zearalenone on Puberty Timing, Hypothalamic Nuclei of AVPV and ARC, and Reproductive Functions in Female Mice

Reproductive Sciences ◽

10.1177/1933719116683808 ◽

2016 ◽

Vol 24 (9) ◽

pp. 1293-1303 ◽

Cited By ~ 4

Author(s):

Rahmatollah Parandin ◽

Morteza Behnam-Rassouli ◽

Nasser Mahdavi-Shahri

Keyword(s):

Neonatal Exposure ◽

Female Mice ◽

Hypothalamic Nuclei

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Neonatal Exposure to Sevoflurane in Mice Causes Deficits in Maternal Behavior Later in Adulthood

Anesthesiology ◽

10.1097/aln.0000435846.28299.e7 ◽

2014 ◽

Vol 120 (2) ◽

pp. 403-415 ◽

Cited By ~ 34

Author(s):

Yumiko Takaenoki ◽

Yasushi Satoh ◽

Yoshiyuki Araki ◽

Mitsuyoshi Kodama ◽

Ryuji Yonamine ◽

...

Keyword(s):

Hydrogen Gas ◽

Developing Brain ◽

Neonatal Exposure ◽

General Anesthetics ◽

Learning Abilities ◽

Brain Functioning ◽

Female Mice ◽

Maternal Behaviors ◽

Brain Functions ◽

Anesthetic Exposure

Abstract Background: In animal models, exposure to general anesthetics induces widespread increases in neuronal apoptosis in the developing brain. Subsequently, abnormalities in brain functioning are found in adulthood, long after the anesthetic exposure. These abnormalities include not only reduced learning abilities but also impaired social behaviors, suggesting pervasive deficits in brain functioning. But the underlying features of these deficits are still largely unknown. Methods: Six-day-old C57BL/6 female mice were exposed to 3% sevoflurane for 6 h with or without hydrogen (1.3%) as part of the carrier gas mixture. At 7–9 weeks of age, they were mated with healthy males. The first day after parturition, the maternal behaviors of dams were evaluated. The survival rate of newborn pups was recorded for 6 days after birth. Results: Female mice that received neonatal exposure to sevoflurane could mate normally and deliver healthy pups similar to controls. But these dams often left the pups scattered in the cage and nurtured them very little, so that about half of the pups died within a couple of days. Yet, these dams did not show any deficits in olfactory or exploratory behaviors. Notably, pups born to sevoflurane-treated dams were successfully fostered when nursed by control dams. Mice coadministered of hydrogen gas with sevoflurane did not exhibit the deficits of maternal behaviors. Conclusion: In an animal model, sevoflurane exposure in the developing brain caused serious impairment of maternal behaviors when fostering their pups, suggesting pervasive impairment of brain functions including innate behavior essential to species survival.

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