{"title":"Beyond a single signal: how can bovine pregnancy be established without IFNT?","authors":"Toshihiro Sakurai, Hanako Bai, Kazuya Kusama, Kazuhiko Imakawa","doi":"10.1262/jrd.2026-051","DOIUrl":"https://doi.org/10.1262/jrd.2026-051","url":null,"abstract":"<p><p>Interferon tau (IFNT) has been regarded as the dominant conceptus signal for maternal recognition of pregnancy (MRP) in ruminants. In cattle, IFNT is classically proposed to prevent luteolysis by suppressing uterine luteolytic pulses of prostaglandin F2α (PGF2α). IFNT also induces endometrial interferon-stimulated genes (ISGs) such as ISG15, MX dynamin-like GTPase 2 (MX2), and 2'-5'-oligoadenylate synthetase 1 (OAS1), thereby supporting uterine receptivity and an attachment- supportive immune milieu. A recent loss-of-function report using conceptuses lacking functional IFNT challenges this view by describing conceptus elongation and persistence of luteal function in a subset of recipients despite markedly reduced uterine ISG induction during the peri-implantation window. Here, we interpret this claim conservatively and specify experimental boundary conditions that currently limit generalization, including somatic cell nuclear transfer (SCNT), multi-embryo transfer, limited sample size, and the absence of direct physiological readouts of PGF2α pulsatility and the estrogen receptor 1 (ESR1) and oxytocin receptor (OXTR) axis. We then summarize possible buffering routes that could support early pregnancy when IFNT input is weakened, focusing on prostaglandin network rerouting toward luteoprotective outputs such as PGE2, extracellular vesicle (EV)-mediated communication, steroid-immune interactions, and corpus luteum (CL) gating of luteolytic sensitivity. Finally, we discuss how bovine endogenous retrovirus (BERV) long terminal repeats (LTRs) retaining interferon-responsive motifs, including interferon-stimulated response elements (ISREs), gamma-activated sequences (GAS), and ETS-family motifs, may act as enhancer substrates that amplify cytokine inputs in a cell-type and chromatin-dependent manner. Overall, we suggest that IFNT should be evaluated as a frequently dominant signal within a system that includes parallel buffering routes, such that the apparent requirement for IFNT can vary with conceptus load, uterine endocrine conditions, and ERV-derived regulatory architecture.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Preimplantation culture conditions and later-life outcomes: implications for evaluating embryo culture media.","authors":"Jannatul Ferdous Jharna, Md Wasim Bari, Sakino Furusato, Kaname Sato, Yui Maruhashi, Norermi Firzana Alfian, Masahiro Horizoe, Yoshiya Morishita, Kei Uechi, Satoshi Kishigami","doi":"10.1262/jrd.2026-041","DOIUrl":"https://doi.org/10.1262/jrd.2026-041","url":null,"abstract":"<p><p>Environmental conditions during early development are critical determinants of lifelong health, as described by the Developmental Origins of Health and Disease (DOHaD) concept. Preimplantation embryos develop entirely within artificial culture systems during assisted reproduction, yet current media are primarily evaluated by short-term developmental outcomes. Accumulating evidence indicates that embryos cultured in vitro differ from in vivo embryos at metabolic and molecular levels and that altered early nutrition can program long-term phenotypes. Here, we discuss how culture medium composition influences embryonic cellular physiology, focusing on nucleolar organization as an indicator of cellular stress. We propose that embryo culture media should be reconsidered using physiological indices linked to long-term safety rather than developmental performance alone.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fernando López-Gatius, Mónica Pando, Irina Garcia-Ispierto
{"title":"Effect of post-insemination GnRH analogue administration on pregnancy rates in repeat-breeder cows: comparison of dosage and frequency.","authors":"Fernando López-Gatius, Mónica Pando, Irina Garcia-Ispierto","doi":"10.1262/jrd.2026-043","DOIUrl":"https://doi.org/10.1262/jrd.2026-043","url":null,"abstract":"<p><p>Repeat-breeder cows (defined as having > 3 inseminations) significantly impact dairy profitability worldwide. This study evaluated the clinical efficacy of two elevated doses of the GnRH analogue, dephereline, administered during the early luteal phase (5-7 days post-insemination) to improve fertility in high-producing repeat-breeder cows (n = 551). Cows were assigned to a control group (n = 82), a 2 DEPH group (two single doses 24 h apart; n = 235), or a 2.5 DEPH group (a 2.5-fold single dose; n = 234). Pregnancy was recorded in 232 (42.1%) cows: 32 (39%), 100 (42.6%), and 100 (42.7%), in the control, 2DEPH and 2.5DEPH, respectively. Compared to the control, both treatment protocols significantly increased the probability of additional corpus luteum formation in pregnant cows (OR: 5.4 and 8.6, respectively) and reduced pregnancy loss (OR: 0.3 and 0.4, respectively). These findings suggest that both elevated dephereline regimens effectively enhance luteal support and pregnancy maintenance, offering practical therapeutic options for clinical management.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147839270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Holding temperature to transport immature bovine oocytes in collection media critically affects their developmental competence.","authors":"Kenichiro Sakaguchi, Thomas Chia-Tang Ho, Moeka Saito, Takashi Tanida, Yojiro Yanagawa, Seiji Katagiri, Kohei Kawano","doi":"10.1262/jrd.2026-042","DOIUrl":"https://doi.org/10.1262/jrd.2026-042","url":null,"abstract":"<p><p>We investigated the holding condition in collection media to establish transportation system of immature bovine cumulus-oocyte complexes (COCs). We examine holding temperature (38℃ or 20℃), basal media (Lactated Ringer's solution and TCM199) and supplementation of hypoxanthine, an inhibitor of meiotic resumption. As a result, no blastocyst was obtained from COCs held at 38℃ for 6 h or longer, whereas blastocysts were obtained even after 24 h holding in all experimental groups held at 20℃. The blastulation rate was maintained (42%) in TCM199 with hypoxanthine group even after 12 h holding, while reduction of the blastulation rates were observed in all other groups (P < 0.05). After 24 h of storage, Lactated Ringer's solution without hypoxanthine showed the highest blastulation rate (40%). In conclusion, holding temperature of oocytes critically affects the developmental competence of oocytes, and oocytes held at 20°C maintain their developmental competence at least 12 h.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Malonic acid promotes glycolytic activity in cumulus cells and improves the quality of bovine oocytes matured in vitro.","authors":"Nobuhiko Itami, Yuji Hirao","doi":"10.1262/jrd.2025-104","DOIUrl":"https://doi.org/10.1262/jrd.2025-104","url":null,"abstract":"<p><p>Malonic acid (MA) is a dicarboxylic acid that inhibits the mitochondrial electron transport chain. Cumulus cells surrounding human oocytes that achieve conception after in vitro fertilization (IVF) contain higher levels of MA than those that do not. Although MA has no effect on embryo developmental culture, the effects of MA on cumulus cells and oocyte quality remain unclear. In this study, the addition of 10 μM MA to the in vitro maturation (IVM) medium cultured cumulus cell-oocyte complexes improved embryo production efficiency, meeting multiple conception-related criteria after IVF (P < 0.05). MA did not affect the nuclear maturation rate of oocytes after IVM; however, it increased lipid content and normal alignment ratio of cortical granules (P < 0.05), both of which are indicators of cytoplasmic maturation of oocytes. MA also increased the adenosine triphosphate (ATP) content in oocytes only when they were present with cumulus cells (P < 0.05). MA decreased mitochondrial membrane potential activity in cumulus cells but increased the ATP content and enhanced glycolytic activity (P < 0.05). The use of a glycolysis inhibitor resulted in a decrease in the ATP content of both cumulus cells and oocytes and reduced the amount of lipids in oocytes (P < 0.05). These results indicate that MA shifts ATP production in cumulus cells from the mitochondrial to the glycolytic pathway, resulting in improved ATP synthesis. Furthermore, an increased ATP supply from cumulus cells to oocytes promotes oocyte cytoplasmic maturation, leading to improved quality of IVF embryos.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147774665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Monosodium glutamate protects DNA of freeze-dried somatic cells and improves development of somatic cell nuclear transfer embryos.","authors":"Kosuke Tanaka, Ai Namiki, Natsuki Ushigome, Kango Yamaji, Daiyu Ito, Sayaka Wakayama, Teruhiko Wakayama","doi":"10.1262/jrd.2026-036","DOIUrl":"https://doi.org/10.1262/jrd.2026-036","url":null,"abstract":"<p><p>Freeze-dried (FD) somatic cells serve as a novel method for preserving animal genetic resources; however, the efficiency of cloned mice production from FD somatic cells remains low, owing to severe nuclear damage induced by the freeze-drying. In this study, we aimed to mitigate FD-induced damage by evaluating protectants that have been reported to exert protective effects during freeze-drying of microorganisms, and to identify those most effective for somatic cells. Results showed, that using Tris-EGTA as the basal medium for freeze-drying, together with monosodium glutamate (MSG) as a protective agent, significantly reduced DNA damage in FD somatic cells after injection into oocytes. Subsequent optimization of MSG concentration revealed that the addition of 3% MSG markedly increased the formation rate of premature chromosome condensation from 50.0% to 80.4% compared with the non-MSG condition. Moreover, the rate of normal chromosome segregation at the two-cell stage of cloned embryos increased from 0% to 20.0%. Furthermore, although no blastocysts were obtained in the absence of MSG, the addition of 3% MSG enabled the formation of morphologically good-quality blastocysts, albeit at a low frequency. These findings indicated that the addition of 3% MSG reduces DNA damage in FD somatic cells and improves the developmental competence of somatic cell nuclear transfer embryos, representing the first step toward the practical application of FD somatic cells as genetic resources.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147723215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detection of sex chromosome-specific DNA sequences by polymerase chain reaction using hair DNA in cattle.","authors":"Toma Hamano, Tomomi Kanazawa, Toru Takahashi","doi":"10.1262/jrd.2025-086","DOIUrl":"https://doi.org/10.1262/jrd.2025-086","url":null,"abstract":"<p><p>To establish a simpler polymerase chain reaction (PCR) strategy for detecting sex chromosome-specific DNA sequences in cattle, we verified the feasibility of using hair-derived DNA as a PCR template. In the control steer, multiplex PCR using hair-derived DNA resulted in the amplification of two amplicons: one derived from the X chromosome-harboring 1.715 satellite DNA (365 bp) and another from the Y chromosome-harboring btDYZ-1 sequence (199 bp). In heterosexual twin females with XX/XY chimerism confirmed by chromosome analyses, multiplex PCR analyses with hair DNA determined both 365 and 199 bp amplicons in five of the six cases. In the remaining case, multiplex PCR analysis using hair DNA revealed the amplification of only the 365-bp product; however, using singleplex PCR, the 199-bp product was successfully amplified from hair DNA. The results of the present study suggest that sex chromosome-specific DNA sequences can be detected by PCR using bovine hair-derived DNA.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147690762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jakub Bartlewski, Maria Emilia Franco Oliveira, Pawel M Bartlewski
{"title":"Effects of a GnRH antagonist on antral follicular development and ovarian hemodynamics in cycling ewes.","authors":"Jakub Bartlewski, Maria Emilia Franco Oliveira, Pawel M Bartlewski","doi":"10.1262/jrd.225-109","DOIUrl":"10.1262/jrd.225-109","url":null,"abstract":"<p><p>Sixteen multiparous Santa Inês ewes underwent transrectal ovarian ultrasonography from days 6 to 17 (D6-17; D0 = ovulation). On D6, ewes received a single subcutaneous injection of Firmagon<sup>®</sup> at a low dose (LD; n = 5; 215 µg/kg body weight [b.w.]) or a high dose (HD; n = 6; 235 µg/kg b.w.); controls (C; n = 5) received saline. Ovulations were detected in 100% of controls, but only in 20% of LD and 17% of HD animals. Mean daily numbers of large antral follicles (> 4.49 mm) decreased (P < 0.05) between D6 and D7 in HD group. Compared with controls, LD ewes had higher (P < 0.05) ovarian artery pulsatility index (PI; D16-17) and resistive index (RI; D17), but lower flow-propagation velocity (FPV; D17), whereas HD ewes exhibited higher PI (D15) and RI (D17), along with lower FPV (D8 and D15) and end-diastolic velocity (D17). Firmagon<sup>®</sup> treatment was associated with a reduced number of large antral follicles and alterations in ovarian blood perfusion.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":"80-85"},"PeriodicalIF":2.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Current status and advances in bovine semen production technologies for artificial insemination in Japan.","authors":"Yousuke Naniwa, Masashi Kinukawa, Kyoko Uchiyama","doi":"10.1262/jrd.2025-141","DOIUrl":"10.1262/jrd.2025-141","url":null,"abstract":"<p><p>Artificial insemination (AI) is the predominant reproductive technology in Japanese cattle breeding, particularly for genetic improvement of dairy and beef cattle. This review outlines the historical development, current status, and recent advances in semen production technologies for AI in Japan and addresses the remaining challenges and future directions. The adoption of AI accelerated after the Act on Improvement and Increased Production of Livestock was implemented in 1950, with frozen semen replacing liquid semen by the mid-1960s. Advances in cryobiology and genomic selection have improved breeding efficiency; however, fertility issues persist. In dairy cattle, conception rates have declined primarily due to high milk yield, negative energy balance, and heat stress. In beef cattle, particularly Japanese Black cattle, conception rates remain stable overall, but subfertile sires still occur despite normal post-thaw semen quality. Studies on sperm motility, acrosomal integrity, and genomic variants have identified a single nucleotide polymorphism (SNP) marker linked to extreme subfertility in Japanese Black bulls. Japan has developed innovative technologies such as the two-layer semen straw (FCMax), which enhances post-thaw sperm function through in-straw dilution and supplementation. Field trials have suggested potential improvements in conception rates; however, large-scale validation studies are still ongoing. Furthermore, sexed semen technology has been widely adopted in Japan and achieved conception rates comparable to those of conventional semen. Emerging challenges include labor efficiency in large-scale farms, prompting interest in improved thawing protocols or liquid semen alternatives. Future priorities include integrating genomic tools, refining cryobiological techniques, and implementing practical innovations to sustain cattle reproduction in evolving production systems.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":"39-47"},"PeriodicalIF":2.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Development of a three-dimensional culture model of endometrium to study embryo-uterine interactions.","authors":"Nobuhiko Yamauchi","doi":"10.1262/jrd.2025-102","DOIUrl":"10.1262/jrd.2025-102","url":null,"abstract":"<p><p>Three-dimensional (3D) culture systems provide physiologically relevant models that better replicate in vivo cell architecture and function compared to the conventional two-dimensional cultures. In reproductive biology, 3D models of endometrial cells have emerged as powerful tools to investigate uterine physiology, embryo-maternal interactions, and implantation processes. Gel-based cultures using natural extracellular matrices such as collagen or Matrigel enable endometrial epithelial and stromal cells to form gland-like or fibroblast-like structures while maintaining hormone responsiveness and secretory activity. In addition, spheroid cultures recapitulate cell polarity, paracrine signaling, and tissue remodeling, offering insights into implantation biology and endometrial pathologies such as endometriosis. Our studies have demonstrated that bovine endometrial epithelial cells embedded in Matrigel exhibit enhanced glandular gene expression and that engineered hetero-spheroids provide stable models for studying interferon-induced matrix remodeling. Furthermore, co-culture of cultured endometrial explants with rat hatched blastocyst facilitates in vitro analysis of embryo attachment and uterine receptivity. Advances in organoid and microfluidic platforms extend these models by enabling long-term culture and dynamic hormonal regulation. Collectively, 3D culture approaches bridge the gap between in vitro experimentation and in vivo physiology, offering translational applications in reproductive medicine, livestock fertility management, and drug discovery.</p>","PeriodicalId":16942,"journal":{"name":"Journal of Reproduction and Development","volume":" ","pages":"34-38"},"PeriodicalIF":2.2,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145917929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}