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      Effect of dehydroepiandrosterone on meiotic spindle structure and oocyte quality in mice

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          Abstract

          Objective(s):

          Dehydroepiandrosterone (DHEA) has been reported to improve pregnancy chances in women with diminished ovarian reserve (DOR) and to reduce miscarriage rates by 50–80%. This study, therefore, assesses effects of DHEA on number of retrieved oocytes and meiotic spindles.

          Materials and Methods:

          A randomized, prospective, controlled study was conducted on eight groups, four groups of young mice and four elderly. All young and old groups received different oral doses (35, 50, 75 mg/kg) of DHEA for 3 months. Meiotic spindle assessment was done by immunocytochemical techniques using a confocal laser microscope (Leica TCS-4D).

          Results:

          Statistical surveys showed that in control young groups 80% ( P=0.0845) and in the old control group 73.3% ( P=0.000) of the meiotic spindles have a normal shape and structure; the difference was meaningful. The young with 50 mg/kg of DHEA in 85.4% and the young with 75 mg/kg of DHEA in 84.2% were normal in shape and structure. Statistical analysis showed that the difference was meaningless ( P=0.845). The old group with 30 mg/kg of DHEA in 81.1%, the old with 50 mg/kg of DHEA in 83.9%, and the old with 75 mg/kg of DHEA in 79.0% showed normal shape and structure. The meiotic spindle disruption ratio in old mice showed a significant difference ( P=0.000) in comparison with others in young groups. Statistical analysis showed that difference between DHEA and control groups is meaningful. But this difference was meaningless between DHEA groups.

          Conclusion:

          Results showed that DHEA has a positive and improvement effect on the meiotic spindle in old mice.

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          Most cited references45

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          Androgen production in women.

          To describe the sources, production rates, circulating concentrations, and regulatory mechanisms of the major androgen precursors and androgens in women. Review of the major published literature. Quantitatively, women secrete greater amounts of androgen than of estrogen. The major circulating steroids generally classified as androgens include dehydroepiandrosterone sulphate (DHEAS), dehydroepiandrosterone (DHEA), androstenedione (A), testosterone (T), and dihydrotestosterone in descending order of serum concentration, though only the latter two bind the androgen receptor. The other three steroids are better considered as pro-androgens. Dehydroepiandrosterone is primarily an adrenal product, regulated by adrenocorticotropic hormone (ACTH) and acting as a precursor for the peripheral synthesis of more potent androgens. Dehydroepiandrosterone is produced by both the ovary and adrenal, as well as being derived from circulating DHEAS. Androstenedione and testosterone are products of the ovary and the adrenal. Testosterone circulates both in its free form, and bound to protein including albumin and sex steroid hormone-binding globulin (SHBG), the levels of which are an important determinant of free testosterone concentration. The postmenopausal ovary is an androgen-secreting organ and the levels of testosterone are not directly influenced by the menopausal transition or the occurrence of menopause. Dihydrotestosterone (DHT) is primarily a peripheral product of testosterone metabolism. Severe androgen deficiency occurs in hypopituitarism, but other causes may lead to androgen deficiency, including Addison's disease, corticosteroid therapy, chronic illness, estrogen replacement (leads to elevated SHBG and, therefore, low free testosterone), premenopausal ovarian failure, or oophorectomy.
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            Prevention of maternal aging-associated oocyte aneuploidy and meiotic spindle defects in mice by dietary and genetic strategies.

            Increased meiotic spindle abnormalities and aneuploidy in oocytes of women of advanced maternal ages lead to elevated rates of infertility, miscarriage, and trisomic conceptions. Despite the significance of the problem, strategies to sustain oocyte quality with age have remained elusive. Here we report that adult female mice maintained under 40% caloric restriction (CR) did not exhibit aging-related increases in oocyte aneuploidy, chromosomal misalignment on the metaphase plate, meiotic spindle abnormalities, or mitochondrial dysfunction (aggregation, impaired ATP production), all of which occurred in oocytes of age-matched ad libitum-fed controls. The effects of CR on oocyte quality in aging females were reproduced by deletion of the metabolic regulator, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α). Thus, CR during adulthood or loss of PGC-1α function maintains female germline chromosomal stability and its proper segregation during meiosis, such that ovulated oocytes of aged female mice previously maintained on CR or lacking PGC-1α are comparable to those of young females during prime reproductive life.
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              Influence of maternal age on meiotic spindle assembly in oocytes from naturally cycling women.

              To examine the effects of maternal ageing on the meiotic apparatus, we obtained oocytes from naturally cycling women in two age groups, including younger (aged 20-25 years) and older (aged 40-45 years) women. Using high-resolution confocal microscopy we obtained a detailed picture of the meiotic spindle and chromosome placement during various phases of meiosis. Our data revealed that the meiotic spindle in older women is frequently abnormal, both with regard to chromosome alignment and the microtubule matrix that comprise the meiotic spindle. The spindle in 79% of the oocytes from the older group exhibited abnormal tubulin placement and one or more chromosomes were displaced from the metaphase plate during the second meiotic division. In contrast, only 17% of the oocytes from the younger age group exhibited aneuploid conditions. The majority of eggs from this group possessed a well ordered, meiotic spindle containing chromosomes that were fully aligned within a distinct metaphase plate in the spindle. Chromosome management during meiosis is directed by microtubule assembly within the spindle. These data suggest that the regulatory mechanisms responsible for assembly of the meiotic spindle are significantly altered in older women, leading to the high prevalence of aneuploidy.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                October 2018
                : 21
                : 10
                : 1020-1025
                Affiliations
                [1 ]Physiology Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
                [2 ]Fertility and Infertility Research Center, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
                [3 ]Department of Anatomical Science, Faculty of Medicine, Tarbiat Modarres University, Tehran, Iran
                [4 ]Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Science, Ahvaz, Iran
                Author notes
                [* ]Corresponding author: Ghasem Saki. Physiolog Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Tel: +98-611-3738073; Email: saki-gh@ajums.ac.ir
                Article
                10.22038/IJBMS.2018.27111.6629
                6281067
                e9b7d574-7e91-4b80-8501-b881e63c6d9b

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 October 2017
                : 21 April 2018
                Categories
                Original Article

                dehydroepiandrosterone meiotic spindle,mice,oocyte quality,pregnancy

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