About

Dr. Heewon Seo is an Assistant Professor in the Department of Animal and Avian Sciences at the University of Maryland. He is a reproductive biologist whose research focuses on understanding the cellular and molecular interactions between the conceptus and uterus during implantation and placentation. His long-term goal is to apply this knowledge to develop clinical strategies aimed at reducing infertility and preventing pregnancy loss in women and domestic livestock. Dr. Seo utilizes livestock species such as pigs, sheep, and cows to conduct comparative studies across different types of implantation and placentation. His research emphasizes the investigation of the temporal and spatial changes in the metabolism of specific cell types within the uterus and placenta during the critical events of implantation and early placental development. His work aims to elucidate the physiological, cellular, and molecular events that support successful pregnancy, contributing valuable insights into reproductive biology.

Research topics

• Biology
• Endocrinology
• Medicine
• Andrology
• Internal medicine
• Cell biology
• Genetics
• Biochemistry

Selected publications

• PSV-7 The reproductive tract microbiota of cyclic and pregnant gilts.

  Journal of Animal Science · 2025-10-01

  articleOpen access

  Abstract The composition of bacterial communities within the female reproductive tract has been associated with fertility status in mammals; however, limited research has explored reproductive tract microbiota in swine. The objective of this study was to analyze the abundance and diversity of bacterial communities from the mucosal surface of the vagina, cervix, uterus, and chorioallantois, and within the allantoic and amniotic fluids throughout gestation in gilts. Duroc x Landrace x Yorkshire gilts (n=38) free of physical, health or reproductive-related issues were euthanized and hysterectomized on either day 11 (n = 11; peri-implantation), 15 (n = 10; implantation), 60 (n =6; mid-gestation) or 90 (n = 6; late-gestation) of pregnancy, as well as day 15 (n = 5; cyclic) of the estrous cycle. Bacterial analyses were conducted targeting the V4 hypervariable region of the 16S rRNA gene. In day 15 cyclic gilts, genera Campylobacter, Actinobacillus, Anaerococcus, and Fusobacterium were more abundant in the vagina than in the cervix (P < 0.05). Additionally, Campylobacter, Porphyromonas, and Anaerococcus were more abundant in the vagina than in the endometrium (P < 0.05). In pregnant gilts, the genus Fusobacteria abundance was greater in the vagina than in the cervix and endometrium on days 11 (P < 0.01) and 15 (P < 0.01) of gestation. Additionally, Lactobacillus was more abundant in allantoic fluid than the endometrium on day 60 (P < 0.05). Further, Streptococcus, Campylobacter, and Actinobacillus were more abundant in the vagina than in the amniotic fluid on day 90 (P < 0.05). Alpha diversity metrics indicated lower microbial diversity in amniotic fluid relative to other tissues (P < 0.05). However, alpha diversity did not differ between cyclic and pregnant gilts (P > 0.05). Beta diversity analysis revealed distinct clustering patterns based on tissue type and stage of pregnancy. Specifically, the vagina, cervix, and endometrium clustered separately from placental fluids. Additionally, microbial communities in samples from day 15 cyclic, day 11 pregnant, and day 15 pregnant gilts clustered distinctly from days 60 and 90 of gestation (P < 0.01). These findings suggest that microbial communities within the reproductive tract are dynamic and vary by both anatomical location and stage of pregnancy or estrous cycle. The distinct clustering of microbial populations between early and late stages of gestation indicates shifts in bacterial composition potentially associated with the presence of a conceptus. Additionally, the observed differences in microbial diversity across reproductive tissues and fetal fluids highlight potential functional roles of microbiota in reproductive success.

  PublisherOA PDFDOI

• Effects of dietary supplementation of creatine on fetal development in gilts at d 60 and d 90 of gestation

  Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology · 2025-03-01 · 4 citations

  articleOpen access

  BACKGROUND: The creatine-creatine kinase-phosphocreatine (Cr-CK-PCr) system maintains intracellular ratios of ATP/ADP for support of cellular functions and has been characterized at the placental-uterine interface of rodents, primates, swine and sheep, and thus may support fetal development. This study determined effects of dietary supplementation of creatine (Cr) to gestating gilts on fetal development, the number and ratio of primary and secondary muscle fibers, and on protein expression in endometrium and fetal biceps-femoris muscle, respectively in fetal pigs on d 60 and d 90 of gestation. METHODS: Reproductively mature gilts were synchronized to estrus using Matrix, observed for estrus (d 0), and artificially inseminated 12 h and 36 h later. Gilts were individually housed and fed 0.86 kg of 14% crude protein diet twice daily that meets nutritional requirements for pregnant gilts. Gilts were assigned to either basal diet control (CON) group, or Cr supplemented group (provided 30 g Cr monohydrate daily) from d 10 to either d 60 or d 90 of gestation. Gilts were euthanized and hysterectomized on either d 60 or d 90 of gestation. These protocols were completed in two replicates, as gilts were bred in spring and euthanized in summer or bred in fall and euthanized in winter (n = 20 gilts/replicate). Litter size, crown-rump length, sex, and fetal weight was recorded. Three female and male fetuses closest to mean litter weight were selected to assess effects of treatment on weight of fetal brain, kidney, liver, spleen, and biceps-femoris muscle. Data were analyzed to determine effects of treatment, days of gestation, replicate, and sex on litter size, fetal measurements, and incidence of intrauterine growth restriction. RESULTS: 0.05). CONCLUSIONS: Results suggest that dietary supplementation of Cr in gestating gilts enhanced development of select fetal organs and contribute to understanding roles of the Cr-CK-PCr system in pregnancy.

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• Conceptus Elongation, Implantation, and Early Placental Development in Species with Central Implantation: Pigs, Sheep, and Cows

  Biomolecules · 2025-07-17 · 6 citations

  reviewOpen access

  Species have different strategies for implantation and placentation. Much can be learned about general molecular and cellular biology through the examination and comparison of these differences. To varying degrees, implantation in all species includes alterations in epithelial polarity, the transformation of the endometrial stroma, the differentiation of the trophoblast, cell-to-cell and tissue-to-tissue signaling through hormones, cytokines, and extracellular vesicles, and the alteration of the maternal immune system. This review focuses on implantation in pigs, sheep, and cows. These species share with mice/rats and humans/primates the key events of early embryonic development, pregnancy recognition, and the establishment of functional placentation. However, there are differences between the pregnancies of livestock and other species that make livestock unique biomedical models for the study of pregnancy and cell biology in general. Pig, sheep, and cow conceptuses (embryo/fetus and associated placental membranes) elongate prior to implantation, displaying central implantation, extended periods of conceptus attachment to the uterus, and epitheliochorial (pigs) and synepitheliochorial (sheep and cows) placentation. This review will discuss what is understood about how the trophoblast and extraembryonic endoderm of pig, sheep, and cow conceptuses elongate, and how a major goal of current in vitro models is to achieve conceptus elongation. It will then examine the adhesion cascade for conceptus implantation that initiates early placental development in pigs, sheep, and cows. Finally, it will conclude with a brief overview of early placental development in pigs, sheep, and cows, with a listing of some important "omics" studies that have been published.

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• Effect of gestational age and fetal sex on metabolism of creatine by uteri, placentae, and fetuses of pigs

  Biology of Reproduction · 2025-01-21 · 4 citations

  article

  The creatine (Cr) biosynthesis pathway buffers adenosine triphosphate in metabolically active tissues. We investigated whether sex of fetus and day of gestation influence Cr in endometrial and conceptus tissues from gilts on days 60 and 90 (n = 6 gilts/day) of gestation. Uterine and conceptus tissues associated with one male and one female fetus from each gilt were analyzed for creatine, messenger RNAs (mRNAs), and proteins for Cr biosynthesis. Total Cr decreased in amniotic fluid but increased in allantoic fluid between days 60 and 90 of gestation for male (P < 0.05) but not for female fetuses (P > 0.05). Endometrial expression of creatine kinase, muscle (CKM), creatine kinase mitochondrial type 1 (CKMT1), and solute carrier family 6, member 8 (SLC6A8) mRNAs increased (P < 0.05) between days 60 and 90 only for female fetuses. On day 60, expression of creatine kinase, brain (CKB) and CKMT1 mRNAs was greater (P < 0.05) for placentae of female than male fetuses. Livers of male fetuses had greater expression of arginine:glycine amidinotransferase (AGAT) and CKB than for females on day 60, while kidneys of female fetuses had greater expression of guanidinoacetate-N-methyltransferase (GAMT) than male fetuses on day 90 (P < 0.05). Localization of GAMT, CKB, CKMT1, and SLC6A8 proteins to uterine and chorionic epithelium was not influenced by gestational age or fetal sex. Arginine-glycine amidinotransferase localized to fetal kidneys and appeared greater on day 90 than on day 60 in both sexes. Thus, expression of the creatine-creatine kinase-phosphocreatine system at the uterine-conceptus interface is affected by gestational age and fetal sex to influence energy homeostasis in pigs.

  PublisherDOI

• Characterization of TNSALP expression and activity in porcine utero-placental tissues

  Reproduction and Fertility · 2025-04-01

  articleOpen access

  Abstract: Tissue non-specific alkaline phosphatase (TNSALP) regulates postnatal phosphate homeostasis, but its role in utero-placental phosphate availability remains poorly understood. Gilts were bred and hysterectomized on Day 60 or Day 90 of gestation (n = 6/day). Phosphate was less abundant in allantoic and amniotic fluids on Day 90 compared to Day 60. TNSALP protein was immunolocalized, and enzymatic activity was quantified and localized in endometrial and chorioallantois tissues. Day had no effect on TNSALP activity in the chorioallantois. In contrast, endometrial TNSALP activity was lower on Day 90 compared to Day 60. Phosphate abundance in allantoic fluid correlated positively with endometrial TNSALP activity on Day 60 but not Day 90. TNSALP protein was abundantly expressed in the endometrium and chorioallantois on both days investigated, with localization to the endometrial, chorionic, and areolar epithelia, as well as stromal cells and endothelium. TNSALP activity was detected in the endothelium of the blood vessels in both the endometrium and chorioallantois, and on the basal surface of the endometrial glands on Day 60 but not Day 90. The endometrial stratum compactum stroma had strong TNSALP activity on Day 60. Weak TNSALP activity was present in the areolar epithelium, with a modest increase in activity on Day 90 compared to Day 60. TNSALP activity was present in the columnar chorionic epithelial cells, with an apparent decrease in activity in the chorioallantois on Day 90 compared to Day 60. These data reveal spatiotemporal changes in TNSALP localization and activity, suggesting its involvement in regulating phosphate availability at the utero-placental interface in swine. Lay Summary: Phosphate is an essential nutrient for fetal growth, but how it is managed during pregnancy is not fully understood. This study explored the role of an enzyme called tissue non-specific alkaline phosphatase (TNSALP) in regulating phosphate availability in the uterus and placenta in pigs in mid- and late pregnancy. Phosphate levels decreased in the fluids surrounding the fetus in late pregnancy. TNSALP was present in the uterus and placenta, and the amount of the enzyme varied depending on the tissue and stage of pregnancy and correlated with changes in phosphate levels. These findings suggest that TNSALP plays a key role in managing phosphate transport from the mother to the fetus in pregnancy to support fetal development.

  PublisherDOI

• Characterization of the expression of XPR1 in ovine utero-placental tissues

  Reproduction · 2025-05-01

  articleOpen access

  In brief: Phosphate plays a critical role in conceptus development, yet the mechanisms regulating utero-placental availability remain underinvestigated. This research characterized the spatiotemporal expression and endocrine regulation of XPR1, a phosphate exporter, in ovine utero-placental tissues, suggesting a potential role of XPR1 in the regulation of utero-placental phosphate availability. Abstract: Phosphate is an essential regulator of conceptus development, but there is limited understanding of mechanisms regulating phosphate availability in utero-placental tissues. These experiments characterized the expression of xenotropic and polytropic retrovirus receptor 1 (XPR1), a phosphate exporter, in ovine utero-placental tissues. In Experiment 1, ewes were hysterectomized on day 1, 9, or 14 of the estrous cycle or day 30, 50, 70, 110, or 125 of pregnancy. Day of the estrous cycle did not affect XPR1 mRNA expression or protein localization. Expression of XPR1 mRNA decreased with day of gestation in placentomes, while XPR1 protein was detectable in uterine epithelia, blood vessels, endometrial stromal cells, myometrium, caruncular stroma, and syncytium of the placentome. In Experiment 2, ewes received daily injections of either corn oil vehicle (CO) or 25 mg progesterone (P4) in vehicle for the first 8 days of pregnancy and were hysterectomized on either day 9, 12, or 125. Endometrial stroma from P4-treated ewes had greater XPR1 immunoreactivity than CO-treated ewes on day 9. On day 125, endometria from P4-treated ewes had decreased expression of XPR1 mRNA compared to CO-treated ewes. Greater XPR1 protein immunoreactivity was present in uterine epithelia and stratum compactum stroma of P4-treated than CO-treated ewes. P4-treated ewes with a singleton fetus tended to have greater expression of XPR1 mRNA in placentomes than CO-treated ewes with a singleton fetus. Collectively, these results suggest a potential role of XPR1 in the regulation of phosphate availability in utero-placental tissues in ruminants.

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• SPARC expression in the mouse decidua, placenta, and fetus: correlations with SPP1 expression

  Placenta · 2025-06-17 · 1 citations

  article
  PublisherDOI

• 95 The microbiomes of reproductive tissues in cyclic and early gestation gilts

  Journal of Animal Science · 2025-06-01

  articleOpen access

  Abstract During early gestation, the conceptus is undergoing elongation and begins to signal maternal recognition of pregnancy (day 12) with implantation occurring at approximately day 15. Additionally, luteolysis occurs in cyclic gilts at approximately day 13 of their estrous cycle. Further, there is limited research examining the reproductive microbiomes during these periods. Therefore, this study characterized the bacterial communities associated with the mucosal surfaces of the vagina, cervix, and uterus in both pregnant and cycling gilts. Duroc x Landrace x Yorkshire gilts (n=17) free of physical, health or reproductive-related issues were euthanized and hysterectomized during the preimplantation (D11) and implantation (D15) stages of pregnancy as well as cyclic (Pregnant D11, n=7; Pregnant D15, n=5; Cyclic D14/15, n=5). Sterile swabs were used to collect, in duplicate, samples from the mucosal surface of each tissue for storage in microcentrifuge tubes at -80°C until sequencing. For uterine and cervical tissues, a 1 cm incision was made in the same location, exposing the endometrium and cervical mucosa. The sterile swab was rotated 8 times and immediately placed in a microcentrifuge tube. For vaginal sampling, a sterile swab was inserted 6 inches past the vulva and rotated 8 times. Bacterial DNA extraction and genome sequencing targeting the V4 hypervariable region of the 16S rRNA gene was conducted by FERA Diagnostics and Biologicals Corp. Statistical analyses were conducted using the GLM procedure in SAS. Across all reproductive tissues, the phylum Bacteroidetes differed by pregnancy status with less relative abundance in cyclic gilts compared to D11 and D15 gilts (9.68 ± 1.71% vs 11.51 ± 1.11% and 15.91 ± 1.17%, respectively; P&amp;lt; 0.01). Within this phylum, the relative abundance of genus Prevotella was the greatest at D15 compared to D11 and cyclic (4.91 ± 0.59% vs. 3.27 ± 0.57% and 2.15 ± 0.87%, respectively; P&amp;lt; 0.05). The phylum Actinobacteria differed by pregnancy status with a greater relative abundance in cyclic gilts compared to D11 and D15 gilts (13.1 ± 1.66% vs. 5.53 ± 1.08% and 6.72 ± 1.13%, respectively; P&amp;lt; 0.01). Within this phylum, the relative abundance of genus Corynebacterium was greater in cyclic gilts compared to D11 and D15 gilts (5.22 ± 0.60% vs. 2.52 ± 0.39% and 2.83 ± 0.41%, respectively; P&amp;lt; 0.01). There were numerous bacteria that differed by tissue type with Campylobacter, Bacteroides, Porphyromonas, Actinobacillus, Anaerococcus, Peptoniphilus, and Fusobacterium being greater in relative abundance in the vagina compared to the cervix and uterus (P&amp;lt; 0.05). These results suggest that microbial communities differ among components of the reproductive tract and by pregnancy status. The differences observed between the reproductive microbiome of pregnant versus cyclic gilts could be influenced by signals from the conceptus.

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• Evidence for metabolism of creatine by the conceptus, placenta, and uterus for production of adenosine triphosphate during conceptus development in pigs

  Biology of Reproduction · 2024-06-05 · 10 citations

  article

  In pigs, the majority of embryonic mortality occurs when free-floating conceptuses (embryos/fetuses and associated placental membranes) elongate, and the uterine-placental interface undergoes folding and develops areolae. Both periods involve proliferation, migration, and changes in morphology of cells that require adenosine triphosphate (ATP). We hypothesize that insufficient ATP in conceptus and uterine tissues contributes to conceptus loss in pigs. Creatine is stored in cells as phosphocreatine for ATP regeneration through the creatine-creatine kinase- phosphocreatine pathway. However, the expression of components of this pathway in pigs has not been examined throughout gestation. Results of qPCR analyses indicated increases in AGAT, GAMT, CKM, CKB, and SLC6A8 mRNAs in elongating porcine conceptuses, and immunofluorescence microscopy localized guanidinoacetate N-methyltransferase, creatine kinase M, and creatine kinase B proteins to the trophectoderm of elongating conceptuses, to the columnar chorionic epithelial cells at the bottom of chorioallantoic troughs, and to endometrial luminal epithelium at the tops of the endometrial ridges of uterine-placental folds on Days 40, 60, and 90 of gestation. Guanidinoacetate N-methyltransferase protein is expressed in endometrial luminal epithelium at the uterine-placental interface, but immunostaining is more intense in luminal epithelium at the bottoms of the endometrial ridges. Results of this study indicate that key elements of the pathway for creatine metabolism are expressed in cells of the conceptus, placenta, and uterus for potential production of ATP during two timepoints in pregnancy with a high demand for energy; elongation of the conceptus for implantation and development of uterine-placental folding during placentation.

  PublisherDOI

• Spatiotemporal modeling reveals high-resolution invasion states in glioblastoma

  Genome biology · 2024-10-10 · 14 citations

  articleOpen access

  BACKGROUND: Diffuse invasion of glioblastoma cells through normal brain tissue is a key contributor to tumor aggressiveness, resistance to conventional therapies, and dismal prognosis in patients. A deeper understanding of how components of the tumor microenvironment (TME) contribute to overall tumor organization and to programs of invasion may reveal opportunities for improved therapeutic strategies. RESULTS: Towards this goal, we apply a novel computational workflow to a spatiotemporally profiled GBM xenograft cohort, leveraging the ability to distinguish human tumor from mouse TME to overcome previous limitations in the analysis of diffuse invasion. Our analytic approach, based on unsupervised deconvolution, performs reference-free discovery of cell types and cell activities within the complete GBM ecosystem. We present a comprehensive catalogue of 15 tumor cell programs set within the spatiotemporal context of 90 mouse brain and TME cell types, cell activities, and anatomic structures. Distinct tumor programs related to invasion align with routes of perivascular, white matter, and parenchymal invasion. Furthermore, sub-modules of genes serving as program network hubs are highly prognostic in GBM patients. CONCLUSION: The compendium of programs presented here provides a basis for rational targeting of tumor and/or TME components. We anticipate that our approach will facilitate an ecosystem-level understanding of the immediate and long-term consequences of such perturbations, including the identification of compensatory programs that will inform improved combinatorial therapies.

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Frequent coauthors

• Fuller W. Bazer

  Marymount University

  71 shared

• Hakhyun Ka

  Yonsei University

  57 shared

• Gregory A. Johnson

  32 shared

• Jangsoo Shim

  Yonsei University

  30 shared

• Greg A. Johnson

  Mitchell Institute

  28 shared

• Guoyao Wu

  Texas A&M University

  27 shared

• Joe W. Cain

  Texas A&M University

  23 shared

• Mingoo Kim

  Hanyang University

  22 shared