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The aim of the present study was to test the hypothesis that uterine bacterial contamination alters the location of ovarian follicle emergence and selection, and inhibits follicle growth and function. Swabs were collected from the uterine body lumen of cattle on days 7, 14, 21 and 28 after parturition. Bacteria were identified by aerobic and anaerobic culture; bacterial growth was scored semiquantitatively and animals were categorized into standard or high bacterial contamination categories on the basis of the number of colonies detected. Follicular growth and function were monitored by daily transrectal ultrasonography, and estimation of plasma FSH, oestradiol and progesterone concentrations. There was no effect of bacterial contamination on plasma FSH concentration profiles or emergence of the ovarian follicle wave. When uterine bacterial growth scores were high on day 7 or day 21 after parturition, fewer first (1\u002F20 versus 15\u002F50; P < 0.05) or second (1\u002F11 versus 13\u002F32; P < 0.05) dominant follicles were selected in the ipsilateral compared with the contralateral ovary, respectively. The diameter of the first dominant follicle was smaller in animals with a high day 7 bacterial score (P < 0.001), dominant follicle growth was slower (P < 0.05) and oestradiol secretion was decreased (P < 0.05). The present study provides evidence for an effect of the uterus on the ovary after parturition, whereby uterine bacteria have a contemporaneous localized effect on ovarian follicle selection and subsequent growth and function, but not on initial emergence.\u003C\u002Fjats:p>","\u003Cjats:p>Các nang trứng ưu thế đầu tiên sau khi sinh được chọn lựa ưu tiên tại buồng trứng đối bên với sừng tử cung đã từng mang thai. Mục tiêu của nghiên cứu hiện tại là kiểm tra giả thuyết rằng ô nhiễm vi khuẩn tử cung làm thay đổi vị trí xuất hiện và chọn lựa của các nang trứng ở buồng trứng, đồng thời ức chế sự tăng trưởng và chức năng của các nang trứng. Mẫu bông đã được lấy từ lòng tử cung của gia súc vào các ngày thứ 7, 14, 21 và 28 sau khi sinh. Vi khuẩn được xác định qua nuôi cấy hiếu khí và kỵ khí; sự phát triển của vi khuẩn được ghi điểm bán định lượng và động vật được phân loại thành các loại ô nhiễm vi khuẩn tiêu chuẩn hoặc cao dựa trên số lượng thuộc địa được phát hiện. Sự tăng trưởng và chức năng của các nang trứng được theo dõi qua siêu âm qua trực tràng hàng ngày, và ước tính nồng độ FSH trong huyết tương, oestradiol và progesterone. Không có ảnh hưởng của ô nhiễm vi khuẩn đến hồ sơ nồng độ FSH trong huyết tương hoặc sự xuất hiện của sóng nang trứng ở buồng trứng. 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From activation of dormant primordial follicles to selection of secondary follicles, locally acting factors have been identified that appear to exert important effects on the growth and differentiation of oocytes and granulosa cells. This article summarizes evidence to support a model for bi-directional paracrine communication that is based on developmental regulation of the delivery and reception of paracrine factors at the oocyte-granulosa cell interface. Transzonal projections that originate from granulosa cells and terminate at the oocyte plasma membrane provide a polarized means to orient the secretory organelles of somatic cells. Characterization of transzonal projections in follicles from normal and genetically modified mice reveals dynamic changes in the density and stability of transzonal projections. On the basis of new data analysing the orientation and cytoskeletal content of transzonal projections in mammalian oocytes, a model is proposed for regulation of paracrine growth factor secretion by follicle-stimulating hormone. These findings have immediate implications for ovarian hyperstimulation protocols and follicle culture models as related to the production of mammalian embryos by assisted reproductive technologies.\u003C\u002Fjats:p>","\u003Cjats:p>Các yếu tố paracrine do noãn bào và tế bào soma tiết ra điều chỉnh nhiều khía cạnh quan trọng của sự phát triển nang buồng trứng sớm ở động vật có vú. Từ việc kích hoạt các nang nguyên thủy ngủ đến việc chọn lọc các nang thứ cấp, đã xác định các yếu tố hoạt động tại chỗ có vẻ như có tác động quan trọng đến sự tăng trưởng và phân hóa của noãn bào và tế bào granulosa. Bài báo này tóm tắt bằng chứng ủng hộ một mô hình cho sự giao tiếp paracrine hai chiều dựa trên việc điều hòa sự vận chuyển và tiếp nhận các yếu tố paracrine tại giao diện giữa noãn bào và tế bào granulosa. Các dự báo xuyên nang từ tế bào granulosa và kết thúc tại màng plasma của noãn bào cung cấp một phương thức phân cực để định hướng các bào quan tiết niệu của các tế bào soma. Việc xác định các dự báo xuyên nang trong các nang từ chuột bình thường và chuột biến đổi gen cho thấy sự thay đổi động trong mật độ và độ ổn định của các dự báo xuyên nang. Dựa trên các dữ liệu mới phân tích sự định hướng và thành phần cytoskeleton của các dự báo xuyên nang trong noãn bào động vật có vú, một mô hình được đề xuất cho sự điều hòa việc tiết các yếu tố tăng trưởng paracrine bởi hormone kích thích nang trứng. 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recent years, exciting progress has been made towards unravelling the complex intraovarian control mechanisms that, in concert with systemic signals, coordinate the recruitment, selection and growth of follicles from the primordial stage through to ovulation and corpus luteum formation. A plethora of growth factors, many belonging to the transforming growth factor-β (TGF-β ) superfamily, are expressed by ovarian somatic cells and oocytes in a developmental, stage-related manner and function as intraovarian regulators of folliculogenesis. Two such factors, bone morphogenetic proteins, BMP-4 and BMP-7, are expressed by ovarian stromal cells and\u002For theca cells and have recently been implicated as positive regulators of the primordial-to-primary follicle transition. In contrast, evidence indicates a negative role for anti-Mullerian hormone (AMH, also known as Mullerian-inhibiting substance) of pre-granulosa\u002Fgranulosa cell origin in this key event and subsequent progression to the antral stage. Two other TGF-β superfamily members, growth and differentiation factor-9 (GDF-9) and BMP-15 (also known as GDF-9B) are expressed in an oocyte-specific manner from a very early stage and play key roles in promoting follicle growth beyond the primary stage; mice with null mutations in the \u003Cjats:italic>gdf-9\u003C\u002Fjats:italic> gene or ewes with inactivating mutations in \u003Cjats:italic>gdf-9\u003C\u002Fjats:italic> or \u003Cjats:italic>bmp-15\u003C\u002Fjats:italic> genes are infertile with follicle development arrested at the primary stage. Studies on later stages of follicle development indicate positive roles for granulosa cell-derived activin, BMP-2, -5 and -6, theca cell-derived BMP-2, -4 and -7 and oocyte-derived BMP-6 in promoting granulosa cell proliferation, follicle survival and prevention of premature luteinization and\u002For atresia. Concomitantly, activin, TGF-β and several BMPs may exert paracrine actions on theca cells to attenuate LH-dependent androgen production in small to medium-size antral follicles. Dominant follicle selection in monovular species may depend on differential FSH sensitivity amongst a growing cohort of small antral follicles. Changes in intrafollicular activins, GDF-9, AMH and several BMPs may contribute to this selection process by modulating both FSH- and IGF-dependent signalling pathways in granulosa cells. Activin may also play a positive role in oocyte maturation and acquisition of developmental competence. In addition to its endocrine role to suppress FSH secretion, increased output of inhibin by the selected dominant follicle(s) may upregulate LH-induced androgen secretion that is required to sustain a high level of oestradiol secretion during the pre-ovulatory phase. Advances in our understanding of intraovarian regulatory mechanisms should facilitate the development of new approaches for monitoring and manipulating ovarian function and improving fertility in domesticated livestock, endangered species and man.\u003C\u002Fjats:p>","\u003Cjats:p>Trong những năm gần đây, đã có những tiến bộ đáng chú ý trong việc khám phá các cơ chế kiểm soát nội buồng trứng phức tạp, phối hợp với các tín hiệu toàn thân, phối hợp việc tuyển chọn, lựa chọn và tăng trưởng của các nang từ giai đoạn nguyên thủy đến giai đoạn rụng trứng và hình thành hoàng thể. Một số lượng lớn các yếu tố tăng trưởng, nhiều yếu tố thuộc siêu họ yếu tố tăng trưởng chuyển dạng beta (TGF-β), được biểu hiện bởi các tế bào soma buồng trứng và noãn bào theo cách liên quan đến giai đoạn phát triển và hoạt động như các điều hòa nội buồng trứng của quá trình tạo nang. Hai yếu tố như vậy, protein hình thành xương, BMP-4 và BMP-7, được biểu hiện bởi các tế bào stroma buồng trứng và\u002Fhoặc tế bào theca và gần đây đã được chỉ ra là các người điều chỉnh tích cực đối với sự chuyển đổi từ nang nguyên thủy sang nang chính. Ngược lại, có bằng chứng cho thấy vai trò tiêu cực của hormone chống Mullerian (AMH, còn được gọi là chất ức chế Mullerian) có nguồn gốc từ tế bào pre-granulosa\u002Fgranulosa trong sự kiện quan trọng này và sự tiến triển sau đó đến giai đoạn antral. Hai thành viên khác của siêu họ TGF-β, yếu tố tăng trưởng và phân hóa-9 (GDF-9) và BMP-15 (còn được gọi là GDF-9B) được biểu hiện theo cách đặc hiệu cho noãn bào từ một giai đoạn rất sớm và đóng vai trò quan trọng trong việc thúc đẩy sự phát triển của nang vượt qua giai đoạn chính; chuột có đột biến null trong gen \u003Cjats:italic>gdf-9\u003C\u002Fjats:italic> hoặc cừu với đột biến bất hoạt trong các gen \u003Cjats:italic>gdf-9\u003C\u002Fjats:italic> hoặc \u003Cjats:italic>bmp-15\u003C\u002Fjats:italic> là vô sinh với sự phát triển nang bị ngừng lại ở giai đoạn chính. Các nghiên cứu về các giai đoạn phát triển nang sau đó cho thấy vai trò tích cực của activin do các tế bào granulosa tiết ra, BMP-2, -5 và -6, BMP-2, -4 và -7 do tế bào theca tiết ra và BMP-6 do noãn bào tiết ra trong việc thúc đẩy sự phát triển của tế bào granulosa, sự sống còn của nang và ngăn ngừa sự trưởng thành hoàng thể sớm và\u002Fhoặc sự thoái hóa. Đồng thời, activin, TGF-β và một số BMP có thể gây ra tác động ngoại tiết trên các tế bào theca để làm giảm sản xuất androgen phụ thuộc LH trong các nang antral nhỏ đến vừa. Việc lựa chọn nang chi phối trong các loài đơn noãn có thể phụ thuộc vào độ nhạy FSH khác nhau giữa một nhóm các nang antral nhỏ đang phát triển. Những thay đổi trong các activin nội nang, GDF-9, AMH và một số BMP có thể góp phần vào quá trình lựa chọn này bằng cách điều chỉnh cả tín hiệu phụ thuộc FSH và IGF trong các tế bào granulosa. Activin cũng có thể đóng vai trò tích cực trong quá trình trưởng thành noãn bào và thu nhận khả năng phát triển. Ngoài vai trò nội tiết của nó trong việc ức chế sự tiết FSH, việc tăng cường sản xuất inhibin bởi các nang chi phối được chọn có thể làm tăng sự tiết androgen do LH kích thích cần thiết để duy trì mức độ cao của sự tiết oestradiol trong giai đoạn trước rụng trứng. Những tiến bộ trong việc hiểu biết các cơ chế điều hòa nội buồng trứng nên tạo điều kiện cho việc phát triển các phương pháp mới để theo dõi và thao tác chức năng buồng trứng cũng như cải thiện khả năng sinh sản ở gia súc nuôi, các loài có nguy cơ tuyệt chủng và con người.\u003C\u002Fjats:p>",{"EN":1025,"VI":1026},"TGF-β superfamily members and ovarian follicle development","Các thành viên trong siêu họ TGF-β và sự phát triển của nang buồng 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However, the function of enhancer of zeste homolog 2 (EZH2) in spermatogenesis and the molecular mechanisms underlying its activity remain poorly defined. Here, we demonstrate that deleting EZH2 promoted spermatogonial differentiation and apoptosis. EZH2 is expressed in spermatogonia, spermatocytes and round and elongated spermatids from stage 9 to 11 but not in leptotene and zygotene spermatocytes. Knocking down\u003Cjats:italic>Ezh2 in vitro\u003C\u002Fjats:italic>using a lentivirus impaired self-renewal in spermatogonial stem cells (SSC\u003Cjats:sub>s\u003C\u002Fjats:sub>), and the conditional knockout of\u003Cjats:italic>Ezh2\u003C\u002Fjats:italic>in spermatogonial progenitors promoted precocious spermatogonial differentiation. EZH2 functions to balance self-renewal and differentiation in spermatogonia by suppressing NEUROG3 and KIT via a direct interaction that is independent of its histone methyltransferase activity. 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