研究者詳細 - 山田　満稔

論文 - 山田　満稔

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子宮頸管妊娠に対しメトトレキサート(MTX)と子宮動脈塞栓術(UAE)を併用し保存的治療を行った2例

白石慧, 上條慎太郎, 佐久間萌子, 大岡令奈, 松沢優一, 内田志穂, 祝井麻希, 内田明花, 山田満稔, 山上亘, 田中守

東京産科婦人科学会会誌（(一社)東京産科婦人科学会） 73 （ 4 ） 848 - 853 2024年10月

ISSN 2186-0599

子宮頸管妊娠は異所性妊娠の一型であり,止血困難に至る疾患である.現在,治療法は子宮を温存する保存的治療法が主体となっている.メトトレキサート(methotrexate:MTX)の投与,子宮動脈塞栓術(uterine artery embolization:UAE)などによる保存的治療法が行われるが,診断基準・治療方針については未だコンセンサスが確立されていない.今回我々は子宮頸管妊娠に対し保存的治療としてMTXとUAEを併用し,子宮温存しえた2症例を経験した.子宮頸管妊娠は早期診断が重要であることに加え,治療経過中に出血をきたすことも多い.緊急での輸血やUAEなど急変に対応できる体制のもとで診断・治療をすることが重要である.(著者抄録)

Calcium oscillations and mitochondrial enzymes in stem cells

Fukuoka M., Kang W., Horiike S., Yamada M., Miyado K.

Regenerative Therapy 26 811 - 818 2024年06月

Calcium oscillations are rhythmic fluctuations of the intracellular concentration of calcium ions (Ca2+). As Ca2+ evokes various cellular processes, its intracellular concentration is tightly regulated. Ca2+ oscillations control biological events, including neuronal differentiation and proliferation of mesenchymal stem cells. The frequency and pattern of Ca2+ oscillations depend on cell type. Researchers have studied Ca2+ oscillations to better understand how cells communicate and regulate physiological processes. Dysregulation of Ca2+ oscillations causes health problems, such as neurodegenerative disorders. This review discusses the potential functions of Ca2+ oscillations in stem cells.

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Overdue Calcium Oscillation Causes Polyspermy but Possibly Permits Normal Development in Mouse Eggs

Fukuoka M., Kang W., Katano D., Horiike S., Miyado M., Tanaka M., Miyado K., Yamada M.

International Journal of Molecular Sciences （International Journal of Molecular Sciences） 25 （ 1 ） 2024年01月

ISSN 16616596

In some non-mammalian eggs, the fusion of one egg and multiple sperm (polyspermy) induces a robust rise in intracellular calcium ion (Ca2+) concentration due to a shortage of inducers carried by a single sperm. Instead, one of the sperm nuclei is selected inside the egg for normal embryogenesis. Polyspermy also occurs during the in vitro fertilization of human eggs; however, the fate of such eggs is still under debate. Hence, the relationship between polyspermy and repetitive Ca2+ increases (Ca2+ oscillation) in mammals remains unknown. To address this issue, we used mouse sperm lacking extramitochondrial citrate synthase (eCS), which functions as a Ca2+ oscillation inducer; its lack causes retarded Ca2+ oscillation initiation (eCs-KO sperm). Elevated sperm concentrations normalize Ca2+ oscillation initiation. As expected, eCS deficiency enhanced polyspermy in both zona pellucida (ZP)-free and ZP-intact eggs despite producing the next generation of eCs-KO males. In conclusion, similarly to non-mammalian eggs, mouse eggs may develop normally under polyspermy conditions caused by problematic Ca2+ oscillation.

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Assessment of embryologist sufficiency and associated regional disparities in Japanese assisted reproduction facilities using nationwide survey data (IZANAMI project)

Shirasawa H., Yamada M., Jwa S.C., Kuroda K., Harada M., Osuga Y.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research） 2024年

ISSN 13418076

Aims: This study aims to comprehensively examine the employment and practices of embryologists in Japan's assisted reproductive technology (ART) laboratories, focusing on the impact of various factors such as ART cycle numbers, add-ons, and regional differences. Additionally, it seeks to assess the extent to which Japanese ART facilities meet international minimum standards set by the American Society for Reproductive Medicine (ASRM). Methods: A survey was conducted from December 2021 to February 2022 among 621 ART facilities in Japan. The study categorized facilities into five ART cycle groups and compared the number of embryologists across these groups. It also examined the correlation between the number of embryologists, ART cycles, add-ons, and regional differences. Data were analyzed using linear regression and multiple linear regression analyses. Results: The study's findings revealed a significant correlation between the total number of embryologists at each facility and the ART cycles. Notably, there were significant differences in the number of embryologists across all ART cycle categories. Of the 435 facilities, only 44.6% met the ASRM minimum embryologist staffing requirement. The regression analysis further highlighted the significance of ART cycles and preimplantation genetic testing for aneuploidies as factors. Moreover, the number of embryologists stationed at urban facilities was significantly higher than at nonurban facilities, indicating a potential regional disparity. Conclusion: In Japan, it was first found that more than 50% of ART facilities do not have sufficient embryologists in place relative to the number of ART cycles. Furthermore, the add-ons and regional differences affect the placement of embryologists.

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Variation in diagnostic methods, criteria, and treatment for chronic endometritis: A nationwide survey in Japan

Jwa S.C., Kuroda K., Shirasawa H., Harada M., Osuga Y., Yamada M.

Journal of Obstetrics and Gynaecology Research 2024年

ISSN 13418076

Aim: To investigate variation in the diagnosis and treatment of chronic endometritis (CE) at the national level in Japan. Methods: We performed a nationwide survey targeting all assisted reproductive technology (ART) facilities across Japan between 2021 and 2022. Diagnostic methods, criteria, and first- and second-line treatment protocols for CE were collected via a questionnaire. Results: Among 616 ART facilities, 437 responded to the survey (response rate: 70.9%) of which 339 (77.6%) implemented diagnosis and treatment of CE. In the diagnosis of CE, 214 (63.1%) facilities used CD138 immunohistochemical staining of endometrial tissue, while hysteroscopy was the most frequently used as an adjunct diagnostic method (241 facilities, 71.1%). The most frequent cutoff value of CD138-positive cells for diagnosing CE was 3–5 cells/20 high-power fields (50%), but 7.9% (17 facilities) and 5.1% (11 facilities) used cutoff values of 1 and 2 cells, respectively. The most common first- and second-line treatment methods were doxycycline (210 facilities, 61.9%) and ciprofloxacin + metronidazole (164 facilities, 48.0%), respectively. Conclusions: There is considerable variation in the number of CD138-positive cells used for diagnosing CE. Establishing unified diagnostic criteria and therapeutic methods for CE is essential to provide standardized medicine for CE at the national level.

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Fertility preservation after gonadotoxic treatments for cancer and autoimmune diseases

Saito S., Yamada M., Yano R., Takahashi K., Ebara A., Sakanaka H., Matsumoto M., Ishimaru T., Utsuno H., Matsuzawa Y., Ooka R., Fukuoka M., Akashi K., Kamijo S., Hamatani T., Tanaka M.

Journal of Ovarian Research （Journal of Ovarian Research） 16 （ 1 ） 2023年12月

Background: The indications for fertility preservation (FP) have expanded. A few patients who underwent gonadotoxic treatment did not have the opportunity to receive FP, leading to concerns that these patients may develop premature ovarian insufficiency. However, the usefulness of FP in women with reduced ovarian reserve has also been questioned. Progestin-primed ovarian stimulation can improve the controlled ovarian stimulation (COS) protocol, but there is limited data on the efficacy of FP with progestin-primed ovarian stimulation. Methods: We conducted a prospective study of 43 women with cancer or autoimmune diseases before and after gonadotoxic treatment at the reproductive unit of Keio University Hospital, counselled between 1 January 2018 and 31 December 2021. After counselling, informed consent was obtained for FP from 43 patients, with those who underwent gonadotoxic treatment of the primary disease being prioritised. Gonadotropin-releasing hormone analogue or progestin was used to suppress luteinising hormone in COS before or after gonadotoxic treatment. The number of cryopreserved mature oocytes was the primary outcome. Results: Forty-three patients and 67 assisted reproductive technology cycles were included in the analysis. The median age at entry was 32 [inter quartile range (IQR), 29–37] years. All patients in the post-gonadotoxic treatment group had their oocytes frozen. Gonadotoxic treatment resulted in fewer oocytes [median 3 (IQR 1–4); pre-gonadotoxic treatment group: five patients, 13 cycles] vs. median 9 (IQR 5–14; pre-gonadotoxic treatment group: 38 patients, 54 cycles; P < 0.001). Although anti-Müllerian hormone levels were lower in the post-gonadotoxic treatment group (n = 5, 13 cycles, median 0.29 (IQR 0.15–1.04) pg/mL) than in the pre-gonadotoxic treatment group (n = 38, 54 cycles, median 1.89 (IQR 1.15–4.08) pg/mL) (P = 0.004), oocyte maturation rates were higher in the post-gonadotoxic treatment group [median 100 (IQR 77.5–100) %] than in the pre-gonadotoxic group [median 90.3 (IQR 75.0–100) %; P = 0.039]. Five patients in the pre-gonadotoxic treatment group had their cryopreserved embryos thawed, of which three had live births. Conclusions: Oocytes obtained for FP from women with cancer or autoimmune disease for FP are of satisfactory quality, regardless of whether they are obtained post-gonadotoxic treatment or COS protocols.

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Fact-finding survey on assisted reproductive technology in Japan

Harada S., Yamada M., Shirasawa H., Jwa S.C., Kuroda K., Harada M., Osuga Y.

Journal of Obstetrics and Gynaecology Research （Journal of Obstetrics and Gynaecology Research） 49 （ 11 ） 2593 - 2601 2023年11月

ISSN 13418076

Aims: In anticipation of the future development of assisted reproductive technology (ART) and to smoothly introduce new technology, it is necessary to understand the current staffing status of the medical system and the current state of treatment, as well as the status of in vitro fertilization add-ons, where the need for insurance coverage is currently a matter of debate. Methods: ART facilities in Japan were surveyed (437 valid responses, response rate: 71%). Current staffing status of the medical system, implementation rates of ART, add-on treatments, and medical supplies were investigated. Results: Despite the abundance of embryologists, nurses, and obstetricians and gynecologists in facilities, the majority of facilities lacked counselors, anesthesiologists, and other essential medical professionals. Conventional ovarian stimulation was widely adopted (median 120 [interquartile range 60–300] cycles), followed by mild ovarian simulation (60 [30–200]). Additionally, freeze–thaw embryo transfer cycles (300 [120–750]) were performed more frequently than fresh embryo transfer cycles (30 [30–60]). Among the add-ons, assisted hatching (85.1%), chronic endometritis examination (77.2%) and treatment (76.9%), artificial oocyte activation (67.3%), endometrial receptivity analysis (64.2%), and endometrial microbiome analysis (58.9%) were relatively widely employed. Conclusions: The implementation of frozen–thawed embryo transfer cycles, freeze-all strategies, and add-on treatments have become popular and widely accepted despite the lack of robust evidence regarding their safety and efficacy.

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保存的に加療し得た卵管間質部妊娠の1例

佐久間萌子, 山田満稔, 松沢優一, 大岡令奈, 福岡美桜, 宮崎康太郎, 木村寛子, 上條慎太郎, 浜谷敏生, 青木大輔, 田中守

東京産科婦人科学会会誌（(一社)東京産科婦人科学会） 72 （ 4 ） 752 - 757 2023年10月

ISSN 2186-0599

卵管間質部妊娠は異所性妊娠の2～4%と稀であり,治療や管理方法に一定の見解が示されていない.今回メトトレキサート(MTX)の全身投与による保存治療が有効であった卵管間質部妊娠の1症例を経験したので報告する.症例は35歳,2妊1産.妊娠6週1日に異所性妊娠疑いにて当院を紹介受診した.妊娠6週6日には血清hCG 2,334.3mIU/mL,画像検査において左卵管角付近に子宮筋層で囲まれた造影効果のある被膜を伴う直径7.2mmの嚢胞を認め,左卵管間質部妊娠と診断した.MTXの全身投与を2回行って奏効を得,MTX治療後142日目に血清hCGは陰転化し,277日目に胎嚢の消失を確認した.502日目に凍結融解胚盤胞移植を行い,正所性妊娠が成立した.MTX療法は卵管間質部妊娠において,次回妊娠時の安全性を考慮した保存治療として有用であると考える.(著者抄録)

Sodium Hexametaphosphate Serves as an Inducer of Calcium Signaling

Katano D., Kang W., Harada Y., Kawano N., Miyado M., Saito T., Fukuoka M., Yamada M., Miyado K.

Biomolecules （Biomolecules） 13 （ 4 ） 2023年04月

In bacteria, polymers of inorganic phosphates, particularly linear polyphosphate, are used as alternative phosphate donors for adenosine triphosphate production. A six-chain form of sodium metaphosphate, sodium hexametaphosphate (SHMP), is believed to have no physiological functions in mammalian cells. In this study, we explored the possible effects of SHMP on mammalian cells, using mouse oocytes, which are useful for observing various spatiotemporal intracellular changes. Fertilization-competent oocytes were isolated from the oviducts of superovulated mice and cultured in an SHMP-containing medium. In the absence of co-incubation with sperm, SHMP-treated oocytes frequently formed pronuclei and developed into two-cell embryos owing to the increase in calcium concentration in the cytoplasm. We discovered an intriguing role for SHMP as an initiator of calcium rise in mouse oocytes, presumably in a wide variety of mammalian cells.

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Embryonic β-Catenin Is Required for Priming of the Uterus to Implantation

Takezawa Y., Iwai M., Fujiki Y., Yokomizo R., Kishigami H., Miyado M., Kawano N., Yamada M., Shindo M., Suzuki M., Sato B., Katano D., Kamijo S., Hamatani T., Tanaka M., Umezawa A., Kang W., Miyado K.

Laboratory Investigation （Laboratory Investigation） 103 （ 3 ） 2023年03月

ISSN 00236837

Repeated implantation failure is a major cause of infertility among healthy women. Uterine β-catenin (CTNNB1) plays a critical role in implantation. However, the role of embryonic CTNNB1 during implantation remains unclear. We addressed this topic by analyzing mice carrying Ctnnb1-deficient (Ctnnb1Δ/Δ) embryos. Ctnnb1Δ/Δ embryos were produced by intercrossing mice bearing Ctnnb1-deficient eggs and sperms. We found that Ctnnb1Δ/Δ embryos developed to the blastocyst stage; thereafter, they were resorbed, leaving empty decidual capsules. Moreover, leukemia inhibitory factor, a uterine factor essential for implantation, was undetectable in Ctnnb1Δ/Δ blastocysts. Furthermore, CDX2, a transcription factor that determines the fate of trophectoderm cells, was not observed in Ctnnb1Δ/Δ blastocysts. Intrauterine injection with uterine fluids (from control mice) and recombinant mouse leukemia inhibitory factor proteins rescued the uterine response to Ctnnb1Δ/Δ blastocysts. These results suggest that embryonic CTNNB1 is required for the secretion of blastocyst-derived factor(s) that open the implantation window, indicating that the uterine response to implantation can be induced using supplemental materials. Therefore, our results may contribute to the discovery of a similar mechanism in humans, leading to a better understanding of the pathogenesis of repeated implantation failure.

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Morphometric assessment of blastocysts: relationship with the ongoing pregnancy rate

Utsuno H., Ishimaru T., Matsumoto M., Sasamori C., Takahashi H., Kimura H., Kamijo S., Yamada M., Tanaka M., Hamatani T.

F and S Reports （F and S Reports） 4 （ 1 ） 85 - 92 2023年03月

Objective: To explore a morphometric grading system for blastocysts that is associated with ongoing pregnancy. Design: Cross-sectional study. Setting: None. Patients(s): All consecutive vitrified blastocysts at our center from July 2018 to November 2021 that were transferred in single blastocyst transfer cycles until January 2022. Intervention(s): None. Main Outcome Measure(s): The ongoing pregnancy rate after a single vitrified-warmed blastocyst transfer. Interobserver agreement on morphometric values among embryologists. Result(s): Three morphometric variables (blastocyst diameter, area of inner cell mass [ICM], and the estimated trophectoderm cell count) were used to evaluate the expansion, ICM, and trophectoderm morphology. During the study period, 585 blastocysts were involved in this study. Of the 3 morphometric variables, ICM area (per 500 μm2, adjusted odds ratio, 1.19; 95% confidence interval, 1.09−1.30) and estimated trophectoderm cell count (per 10 cells, adjusted odds ratio, 1.25; 95% confidence interval, 1.12−1.39) were significantly associated with the ongoing pregnancy rate after adjustment for confounding factors. The ongoing pregnancy rate was 2.0% (1/49) with an ICM area of <2,500 μm2 and the estimated trophectoderm cell count <70. The ongoing pregnancy rate reached 47.8% (22/46) when the ICM area and the estimated trophectoderm cell count were >3,500 μm2 and >110, respectively. Interobserver agreement on the blastocyst diameter, ICM area, and the estimated trophectoderm cell count was excellent-to-good among 5 embryologists (intraclass correlation coefficients: 0.99, 0.87, and 0.91, respectively). Conclusion(s): Morphometric values of ICM and trophectoderm are promising predictors of pregnancy success. The high reproducibility suggests that the morphometric variables will contribute to identifying blastocysts with the highest developmental potential as well as those that will not result in a successful pregnancy.

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Artificial oocyte activation using Ca<sup>2+</sup> ionophores following intracytoplasmic sperm injection for low fertilization rate

Akashi K., Yamada M., Jwa S.C., Utsuno H., Kamijo S., Hirota Y., Tanaka M., Osuga Y., Kuji N.

Frontiers in Endocrinology （Frontiers in Endocrinology） 14 2023年

This large multi-center retrospective study examined whether artificial oocyte activation (AOA) using Ca2+ ionophore following ICSI improves the live birth rate for couples with previous ICSI cycles of unexplained low fertilization rate. In this large-scale multi-center retrospective study conducted in Japan, data were collected from Keio University and 17 collaborating institutions of the Japanese Institution for Standardizing Assisted Reproductive Technology. Between January 2015 and December 2019, 198 couples were included in this study. Oocytes for both the intervention and control groups were procured from the same pool of couples. Oocytes obtained from ICSI cycles with no or low fertilization rate (<50%) with unknown causes were included in the control (conventional ICSI) group while oocytes procured from ICSI cycles followed by performing AOA were assigned to the intervention (ICSI-AOA) group. Those fertilized with surgically retrieved sperm were excluded. ICSI-AOA efficacy and safety were evaluated by comparing these two groups. Live birth rate was the primary outcome. The ICSI-AOA group (2,920 oocytes) showed a significantly higher live birth per embryo transfer rate (18.0% [57/316]) compared to that of the conventional ICSI group with no or low fertilization rate (1,973 oocytes; 4.7% [4/85]) (odds ratio 4.5, 95% confidence interval 1.6–12.6; P<0.05). A higher live birth rate was observed in younger patients without a history of oocyte retrieval. Miscarriage, preterm delivery, and fetal congenital malformation rates were similar between the two groups. ICSI-AOA may reduce fertilization failure without increasing risks during the perinatal period. AOA may be offered to couples with an ICSI fertilization rate < 50%.

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Identification of a syncytin gene in a non-rodent laboratory mammal, Suncus murinus

Suzuki M., Nakamura A., Matsumoto Y., Kang W., Ichinose M., Kawano N., Yamada M., Shindo M., Katano D., Saito T., Harada Y., Miyado M., Miyado K.

Journal of Veterinary Medical Science （Journal of Veterinary Medical Science） 85 （ 9 ） 912 - 920 2023年

ISSN 09167250

An endogenous retrovirus-derived membrane protein, syncytin (SYN), contributes to placental function via trophoblast fusion. Multinuclear trophoblasts (syncytiotrophoblasts) physically and functionally mediate the interaction between fetal and maternal vessels in various ways. Suncus murinus (suncus) is a small mammalian species with a pregnancy duration of approximately 30 days, 1.5 times longer than mice. However, the molecular basis for the longer pregnancy duration is unknown. In this study, we first isolated two genes that encoded putative SYN proteins expressed in the suncus placenta, which were named syncytin-1-like proteins 1 and 2 (SYN1L1 and SYN1L2). When their expression vectors were introduced into cultured cells, suncus SYN1L2 was found to be active in cell fusion. Moreover, the SYN1L2 protein was homologous to a SYN1-like protein identified in greater mouse-eared bats (bat SYN1L) and was structurally compared with bat SYN1L and other SYN proteins, implying the presence of structural features of the SYN1L2 protein.

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【不妊と薬の知識　患者に寄り添う薬剤師になる!】不妊治療に使用される薬の使い方　凍結融解胚移植におけるホルモン調整周期に用いる薬

山田, 満稔

調剤と情報 28 （ 13 ） 2224 - 2228 2022年10月

ISSN 1341-5212

過去10年の間に凍結融解胚移植の実施件数は大幅に増加している。着床をサポートするためには,子宮内膜と胚の発生段階を同期させることが必要である。一般的な子宮内膜の調整方法は,発育中の卵胞から子宮内膜の成熟に必要なエストロゲンとプロゲステロンが順次分泌される自然周期と,これらを順次投与するホルモン調整周期がある。ホルモン調整周期におけるモニタリング方法,およびエストロゲンおよびプロゲステロンの理想的な投与量,投与方法,投与期間を決定するために,さらなる研究が求められている。(著者抄録)

【AYA世代の女性ヘルスケア-対応と実際-】生殖機能維持と保存　生殖補助医療による妊孕性の限界と今後の展望

明石, 一浩, 宇津野, 宏樹 and 山田, 満稔

産婦人科の実際 71 （ 10 ） 1142 - 1149 2022年09月

ISSN 0558-4728

＜文献概要＞女性に対する代表的な妊孕性温存療法には,卵子/受精卵(胚)凍結,卵巣組織凍結が挙げられる。卵子/胚凍結は標準治療の位置づけとして確立しつつある一方,卵巣組織凍結は米国臨床腫瘍学会(ASCO)Clinical Practice Guideline 2018年版ではいまだ実験段階の方法としての位置づけとなっており,有効性・安全性に関する科学的エビデンスの蓄積が求められている。妊孕性温存に向けた実験的な試みとして,in vitro maturation(IVM),卵巣組織凍結における卵胞生存率を高める取り組み,人工卵巣,再生医療による卵子作成などの研究が行われている。本稿では,妊孕性温存療法の実態と限界,今後の展望について解説する。

Trehalose Suppresses Lysosomal Anomalies in Supporting Cells of Oocytes and Maintains Female Fertility

Kang W., Ishida E., Amita M., Tatsumi K., Yonezawa H., Yohtsu M., Katano D., Onozawa K., Kaneko E., Iwasaki W., Naito N., Yamada M., Kawano N., Miyado M., Sato B., Saito H., Saito T., Miyado K.

Nutrients （Nutrients） 14 （ 10 ） 2022年05月

Supporting cells of oocytes, i.e., cumulus cells, control oocyte quality, which determines fertilization success. Therefore, the transformation of mature and immature cumulus cells (MCCs and ICCs, respectively) into dysmature cumulus cells (DCCs) with dead characteristics deteriorates oocyte quality. However, the molecular basis for this transformation remains unclear. Here, we explored the link between autophagic decline and cumulus transformation using cumulus cells from patients with infertility, female mice, and human granulosa cell-derived KGN cell lines. When human cumulus cells were labeled with LysoTracker probes, fluorescence corresponding to lysosomes was enhanced in DCCs compared to that in MCCs and ICCs. Similarly, treatment with the autophagy inhibitor chloroquine elevated LysoTracker fluorescence in both mouse cumulus cells and KGN cells, subsequently suppressing ovulation in female mice. Electron microscopy analysis revealed the proliferation of abnormal lysosomes in chloroquine-treated KGN cells. Conversely, the addition of an autophagy inducer, trehalose, suppressed chloroquine-driven problematic lysosomal anomalies and ameliorated ovulation problems. Our results suggest that autophagy maintains the healthy state of the supporting cells of human oocytes by suppressing the formation of lysosomes. Thus, our results provide insights into the therapeutic effects of trehalose on female fertility.

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治療法の再整理とアップデートのために専門家による私の治療　機能性子宮出血

明石, 一浩 and 山田, 満稔

日本医事新報（ 5114 ） 48 - 49 2022年04月

ISSN 0385-9215

福岡, 美桜, 山田, 満稔, 宇津野, 宏樹, 上條, 慎太郎, 浜谷, 敏生 and 田中, 守

臨床婦人科産科 76 （ 4 ） 239 - 243 2022年04月

ISSN 0386-9865

The possible effects of the Japan Society of Clinical Oncology Clinical Practice Guidelines 2017 on the practice of fertility preservation in female cancer patients in Japan

Kunitomi C., Harada M., Sanada Y., Kusamoto A., Takai Y., Furui T., Kitagawa Y., Yamada M., Watanabe C., Tsugawa K., Nishiyama H., Hosoi H., Miyachi M., Sugiyama K., Maeda Y., Kawai A., Hamatani T., Fujio K., Suzuki N., Osuga Y.

Reproductive Medicine and Biology （Reproductive Medicine and Biology） 21 （ 1 ） 2022年01月

ISSN 14455781

Purpose: In 2017, the first guidelines for fertility preservation in cancer patients were published in Japan. However, the impact of the guidelines remains unknown. Therefore, the authors conducted a nationwide survey on cryopreservation procedures in the period from shortly before to after publication of the guidelines (2016–2019) and compared the results with our previous survey (2011–2015). The authors also surveyed reproductive specialists’ awareness of the guidelines and implementation problems. Methods: The authors sent a questionnaire to 618 assisted reproductive technology facilities certified by the Japanese Society of Obstetrics and Gynecology. Results: The authors received responses from 395 institutions (63.8%). Among them, 144 institutions conducted cryopreservation for cancer patients (vs. 126 in 2011–2015) and performed 2537 embryo or oocyte and 178 ovarian tissue cryopreservation procedures (vs. 1085 and 122, respectively). Compared with the previous period, indications were more varied and protocols for controlled ovarian stimulation were more standardized. Reproductive specialists’ interest in oncofertility was high, but many reported three main difficulties: selecting a treatment method, storing samples in the long term, and securing the necessary human resources. Conclusions: The practice of fertility preservation in cancer patients in Japan has been considerably affected by the first Japanese guidelines.

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Identification of an antibacterial polypeptide in mouse seminal vesicle secretions

Morohoshi K., Yamazaki T., Kito K., Sato B., Kang W., Hibino T., Yoshida M., Yoshida K., Iwamoto T., Yamada M., Miyado K., Kawano N.

Journal of Reproductive Immunology （Journal of Reproductive Immunology） 148 2021年11月

ISSN 01650378

In both men and women, pathogenic bacteria enter the reproductive tract and cause harmful symptoms. Intrauterine and oviductal inflammation after copulation may have severe effects, such as infertility, implantation failure, oviduct obstruction, and robust life-threatening bacterial infection. Human seminal plasma is considered to be protective against bacterial infection. Among its components, Semenogelin-I/-II proteins are digested to function as bactericidal factors; however, their sequences are not conserved in mammals. Therefore, alternative antibacterial (bactericidal and/or bacteriostatic) systems may exist across mammals. In this study, we examined the antibacterial activity in the seminal plasma of mice lacking a gene cluster encoding Semenogelin-I/-II counterparts. Even in the absence of the majority of seminal proteins, antibacterial activity remained in the seminal plasma. Moreover, a combination of gel chromatography and liquid chromatography coupled with tandem mass spectrometry revealed that the prostate and testis expressed 4 protein as a novel antibacterial (specifically, bacteriostatic) protein, the sequence of which is broadly conserved across mammals. Our results provide the first evidence of a bacteriostatic protein that is widely present in the mammalian seminal plasma.

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