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   2021| October-December  | Volume 5 | Issue 4  
    Online since December 30, 2021

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Age-cumulative effect of REC8 reduction on meiotic chromosome segregation errors in mice
Li-Yuan Tian, Ling Zhang, Cheng-Qiu Tao, Xiao-Qi Lin, Feng Zhang, Bin Zhang
October-December 2021, 5(4):193-198
Objective: This study aimed to explore the relationship between cohesin subunit REC8 reduction and meiosis chromosome segregation errors in the ovary. Methods: Rec8+/− mice were generated using CRIPSR/Cas9 gene editing. The association between age and REC8 expression levels in the ovary was determined by Western blotting. Chromosome segregation errors were investigated by immunofluorescence imaging of superovulated oocytes. Wild-type and Rec8+/− female mice at 5, 8, 20, 36, and 40 weeks were used to evaluate ovarian reserve by ovarian clearing and immunolabeling. Results: Ovary REC8 expression levels gradually decreased with age, while chromosome segregation errors increased with age. Segregation errors were more common in Rec8+/− mice, suggesting an association with REC8 expression. The ovarian reserve capacity decreased significantly with age. The ovarian reserve in Rec8+/− mice was inferior to that of age-matched wild-type mice, indicating important roles of age and REC8 levels in the ovarian reserve. Conclusions: REC8 reduction has an age-cumulative effect on meiotic chromosome segregation errors in mouse ovaries. Rec8 haploinsufficiency poses a major challenge in generating normal and reproductive oocytes in aging mice.
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Molecular mechanisms underlying cell-fate specification and cellular diversity of the trophoblast lineage during placental morphogenesis in mice
Jian-Qi Wang, Change Mu, Yang Sun, Jin-Hua Lu, Hai-Bin Wang
October-December 2021, 5(4):220-236
Placental morphogenesis is a highly dynamic process involving mutual recognition and interlacing between the trophoblast–uterus and ultimately the initiation of the maternal–fetal circulatory system. During placental morphogenesis in mice, the trophoblast lineage, which integrates maternal and fetal signaling, undergoes stage-specific changes in gene regulatory programs directing cellular proliferation and fate specification, generating diverse trophoblast subtypes. While accumulating evidence from studies on genetically engineered and mutant mice has revealed the involvement of cell-specific core transcription factors in certain key events during placental morphogenesis, the precise molecular mechanisms by which multipotent trophoblasts gradually differentiate into different subtypes are still largely unknown. In this review, we primarily focus on mutant mouse models with placental phenotypes to provide a comprehensive understanding of the molecular mechanisms underlying cell-fate specification and cellular diversity of the trophoblast lineage during the placental morphogenesis.
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Leukemia inhibitory factor enhanced the developmental and implantation compatibility of mouse embryos in co-culture with human endometrial epithelial cells
Ali Hosseini, Bahar Movaghar, Showra Amani Abkenari, Hassan Nazari, Mehrdad Bakhtiyari
October-December 2021, 5(4):199-205
Objective: Among the various in vitro embryo culture systems, co-culture has demonstrated remarkable effects in pre-implantation embryo development owing to the production of embryo-nourishing factors. Nevertheless, little is known about the secretion of these factors. Therefore, in this study, the effect of leukemia inhibitory factor (LIF), one of the most important nourishing factors in the early development of mouse embryos, in human endometrial epithelial cells (hEECs) was evaluated. Methods: Two-cell stage embryos were collected from the oviducts of hyper-stimulated and mated mice and cultivated in a co-culture with an hEEC monolayer with or without LIF. The quality and developmental and attachment potential rates of cultured embryos were evaluated by determining the levels of octamer-binding transcription factor 4 (Oct4) and caudal type homeobox 2 (Cdx2) transcripts. Results: LIF significantly increased the developmental rate (82.67% vs. 61.04%, respectively) and attachment rate (64% vs. 45.45%, respectively) of mouse embryos co-cultured with hEECs compared to those in untreated embryos. The expression levels of Oct4 and Cdx2 in blastocysts cultured in the presence of LIF were higher than those in blastocysts cultured without LIF. Conclusions: Despite the secretion of LIF by hEECs during co-culture with embryos, the amount of this factor was insufficient, and its addition to the culture media could increase the developmental potential of embryos.
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Altered carcinoembryonic antigen-related cell adhesion molecule 1/T-Cell immunoglobulin mucin-3 signaling causes the dysregulation of decidual CD8+T cells in the third trimester during preeclamptic pregnancies
Chun-Qin Chen, Song-Cun Wang, Feng-Run Sun, Meng-Die Li, Mei-Rong Du, Ying Zhang
October-December 2021, 5(4):206-212
Objective: To investigate the frequency and function of Tim-3+CD8+T cells in the third trimester of normal pregnancies (NPs) and preeclamptic (PE) pregnancies. Methods: T-cell immunoglobulin mucin-3 (Tim-3) expression levels of CD8+T cells in the decidua, peripheral blood, and umbilical cord blood obtained from women showing NPs and PE pregnancies were analyzed using flow cytometry. Decidual CD8+T cells were cultured in the presence of recombinant human carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) protein and/or Tim-3-specific neutralizing antibodies for analyzing CD107a and intracellular cytokine expression. The placental CEACAM1 protein expression was analyzed using immunohistochemistry. Results: Tim-3+CD8+T cells were more abundant in the decidua than in the peripheral blood. Tim-3 expression in the decidual CD8+T cells was significantly lower in PE patients. Decidual Tim-3+CD8+T cells from PE patients expressed higher levels of CD107a and the Th1-type cytokine IFN-γ, but lower levels of the Th2-type cytokine IL-4. CEACAM1 altered the CD107a, IFN-γ, and IL-4 levels; this was reversed by anti-Tim-3 antibodies. The CEACAM1 protein levels were lower in the placental tissues of women with PE pregnancies than in those of women with NPs. Conclusions: Abnormal CEACAM1/Tim-3 regulation may participate in the development of PE, accompanied by disturbed Th2 cell predominance and higher cytotoxicity of decidual CD8+T cells.
  1,272 62 -
Sperm donors in Shanghai, China: A study of motivations, characteristics, and semen parameters of actual sperm donors
Xiao Wang, Min-Xin Chen, Feng Zhang, Guo-Qing Liang, Hong Zhu, Bai-Lan Feng, Zhi-Wen Tao, Feng Jiang
October-December 2021, 5(4):213-219
Objective: To identify the sociodemographic characteristics, motivations, and semen parameters of sperm donors in Shanghai, China. Methods: The participants were sperm donors associated with the Human Sperm Bank of Fudan University in Shanghai, China. Among the 334 sperm donors that applied for participation, 329 completed the survey process. The responses obtained in the questionnaire and face-to-face interviews were used to investigate the donor motivations and characteristics, and the semen quality was examined to identify the sperm parameter. Results: In terms of the sociodemographic characteristics, an altruistic donor in this study was aged between 26 and 30 years, was single, did not have a child, had a college or undergraduate education level, was of the Han ethnicity, and worked full time. The strongest motivation highlighted by sperm donors was a donation for altruistic (26.4%, n = 87) reasons. The second-highest rated motivation was curiosity (20.7%, n = 68), followed by a desire to procreate (17.9%, n = 59). “Complimentary body checks” (14.3%, n = 47) and “financial incentives” (14.7%, n = 47) were regarded as less important. The average semen parameters of the 329 donors were as follows: the semen volume was 3.39 ± 1.21 mL, the semen concentration was 82.75 × 106/mL, the progressive motility rate (PR%) was 63.77% ± 3.13%, the total motility rate was 66.26%, the total progressive motile count was 158.31% ± 54.43 × 106/mL, and the round cell concentration was 0.38 ± 0.51 × 106/mL. The PR% of the procreation motivation group was significantly higher than that of the other motivation groups (P < 0.05). Conclusions: Sperm donors in Shanghai, China, are altruistic about their donation, although curiosity is also a key motivator. In addition, the decisions of donors are culturally influenced, and the motivation to procreate may influence the PR%.
  1,233 65 -
Associations of prepregnancy body mass index, gestational weight gain, and intelligence in offspring: A systematic review and meta-analysis
Si-Meng Zhu, Yi-Chen He, Chen Zhang, Yan-Ting Wu, He-Feng Huang
October-December 2021, 5(4):247-256
Objective: Increasing evidences have shown that prepregnancy maternal weight and gestational weight gain (GWG) may associate with offspring's neurodevelopment. However, the effects of prepregnancy maternal overweight, obesity, and excessive GWG on offspring's intelligence remain controversial. This meta-analysis aimed to re-assess the association between prepregnancy body mass index (BMI), GWG, and children's intelligence. Methods: We systematically searched multiple databases, including PubMed, EMBASE, Cochrane Library, and Ovid Medline, from their inception through February 2021. Studies assessing the association between prepregnancy BMI or GWG and children's intelligence were further screened manually before final inclusion. Cohorts that analyzed the association between prepregnancy BMI or GWG and intelligence of offspring were included, and we used the Mantel–Haenszel fixed-effects method to compute the weighted mean difference (WMD) and 95% confidence interval (CI) of each study. Results:A total of 12 articles were included in this systematic review, while six of them in the meta-analysis. There was a significant full-scale IQ reduction in children born from overweight and obese mothers, with WMDs of −3.08 (95% CI: −4.02, −2.14) and −4.91 (95% CI: −6.40, −3.42), respectively. Compared with control group, the WMDs for performance and verbal intelligence quotient (IQ) were decreased in overweight and obesity groups. However, we observed no association between children's full-scale IQ and excessive GWG with WMD of −0.14 (95% CI: −0.92, 0.65). Conclusions: Women's prepregnancy overweight and obesity adversely associate with children's intelligence but no association with excessive GWG. Our study suggests that further researches focusing on the effect of prepregnancy maternal health on offspring's intelligence development are needed.
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Insights into stem cell therapy for premature ovarian insufficiency
Zhen-Le Pei, Zhe-Yi Wang, Wen-Han Lu, Fei-Fei Zhang, Xin Li, Xiao-Yu Tong, Yi Feng, Cong-Jian Xu
October-December 2021, 5(4):237-246
Hormone therapy, assisted reproductive technology, and regenerative medicine have been used to treat infertility due to premature ovarian insufficiency (POI), with limited success. It is timely to survey the field by outlining the controversies and promising prospects of evolving stem cell (SC) therapy for patients with POI. We first discuss several strategies of tissue-derived SC therapy and induced/engineered SC therapy and then enumerate mechanisms, including cellular regenerability induced in reproductive tissues and paracrine effects induced by various chemokines. Next, we evaluate the potential benefits of SC-based tissue engineering in reversing ovarian aging. Finally, we discuss the clinical feasibility of SC therapy and generalized regenerative medicine for the treatment of POI. In summary, SCs and SC-derived exosomes, induced pluripotent SCs, engineered SCs, and tissue engineering could start a new chapter for fertility rehabilitation in patients with POI. Uncovering the underlying molecular mechanisms and biological efficacy could be facilitated not only by animal experiments but also by security screening and clinical trials to validate SC-based therapy for POI.
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