About

CheMyong Ko is a Professor in the Department of Comparative Biosciences at the University of Illinois College of Veterinary Medicine. He holds a PhD in Developmental Biology from Seoul National University and a BS in Biology Education from the same institution. His research interests focus on studying the molecular mechanisms of ovulation, developing novel methods of contraception for humans and animals, and understanding the impact of endocrine disruptors on reproductive dysfunction. Dr. Ko has contributed to advancing knowledge in reproductive biology through his research, and his work is accessible via PubMed. He is based in Urbana, Illinois, where he continues his research and academic activities.

Research topics

• Biology
• Chemistry
• Medicine
• Internal medicine
• Endocrinology
• Anesthesia
• Cell biology
• Genetics
• Pharmacology

Selected publications

• Estrogen receptor expression in GnRH neurons: back to the future

  Biology of Reproduction · 2026-05-02

  articleSenior author

  Estrogen feedback within the hypothalamic-pituitary-gonadal (HPG) axis is mediated primarily by upstream estrogen-sensitive neuronal populations, most notably kisspeptin neurons, which translate circulating sex steroid levels into excitatory or inhibitory input to gonadotropin-releasing hormone (GnRH) neurons, the final neural output controlling pituitary gonadotropin secretion. Despite extensive research, the expression and role of estrogen receptors in GnRH neurons remain poorly understood. To systematically evaluate what can be inferred from transcriptomic data alone, we conducted a comprehensive analysis of open-source single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets encompassing mouse embryogenesis through adulthood, supplemented by cross-species datasets from rat, squirrel, pig, and human hypothalami. In adult mice, Esr1 transcripts were detected in a distinct subset of Gnrh1+ cells more frequently than Esr2 transcripts. Notably, this expression was dynamic, with an increased proportion of Esr1+Gnrh1+ cells emerging during maturation, particularly after puberty. In contrast, Esr2 detection remained minimal across developmental stages. Pseudotime analysis showed Esr1+Gnrh1+ cells at late pseudotime, coinciding with advanced maturation states. Cross-species comparisons further revealed species-specific patterns, with Esr1+Gnrh1+ cells consistently more prevalent than Esr2+Gnrh1+ cells in rodents, while ESR2+GNRH+ cells were slightly more detectable in pigs and humans. These results support a model where estrogen signaling within GnRH neurons is heterogeneous, developmentally regulated, and often mediated indirectly through upstream estrogen-sensitive circuits, such as kisspeptin and nNOS neurons. This study provides a comprehensive, unbiased transcriptomic framework for understanding estrogen receptor expression in GnRH neurons, offering new insights into how estrogen might influence reproductive function through both direct and indirect signaling pathways.

  PublisherDOI

• Ovarian-Specific Cyp17A1 Overexpression in Female Mice: A Novel Model of Endogenous Testosterone Excess

  Endocrinology · 2025-03-24 · 3 citations

  articleOpen access

  Excessive androgen levels can severely affect female health. However, most existing models of androgen excess rely on exogenous androgen administration, which does not fully capture the effect of elevated local ovarian testosterone on reproductive and metabolic functions. Here, we report the development of a novel hyperandrogenic mouse model, Cyp17TM-625, generated by combining CRISPR-Cas9 and a Tet-On doxycycline system to induce Cyp17A1 overexpression in ovarian theca-interstitial cells. As a result, Cyp17TM-625 mice exhibited significantly elevated Cyp17A1 messenger RNA and protein levels, accompanied by increased testosterone concentrations without alterations in basal levels of estradiol, progesterone, luteinizing hormone, or follicle-stimulating hormone. These mice demonstrated subfertility, evident by smaller and fewer litters, prolonged estrous cycles, and an increased number of unhealthy follicles with abnormally shaped oocytes. Despite these marked reproductive changes, body weight and glucose homeostasis remained comparable to Con-625 mice. Notably, withdrawal of doxycycline reversed testosterone overexpression and restored fertility over time. This model recapitulates reproductive dysfunction but not the metabolic disturbances, commonly observed in exogenous androgen models. The Cyp17TM-625 mouse line is a unique model for investigating the effects of local excess androgens on ovarian function. It also serves as a valuable tool for studying fertility restoration following the withdrawal of testosterone.

  PublisherOA PDFDOI

• Absence of mating behaviors in the female dogs neonatally treated with estrogen and progesterone

  Animal Reproduction · 2025-01-01

  articleOpen accessSenior author

  This study aimed to develop a non-surgical method to neutralize reproduction in female dogs. Female Beagle puppies, aged 6 days, were treated with pellets designed to release estradiol benzoate (EB; 1.0 mg) and progesterone (P4; 5.0 mg) over approximately 3 weeks. Their estrous cycles were monitored from 6 to 34 months of age by examining their vulvas daily and measuring their serum P4 levels once a month. Vulvar edema and discharge, followed by a serum P4 level above 5 ng/ml, indicated the potential estrus. Each time a dog showed these signs, breeding was attempted by housing with a proven male Beagle. All the treated dogs displayed cyclic progesterone surges with 5 to 6-month-long anestrous intervals. Surprisingly, none exhibited sexual behaviors, and no mating occurred (i.e., no intromission and copulatory tie), resulting in no pups being born. This phenomenon was further explored in laboratory animals. Neonatal female rats were treated with microspheres containing smaller doses of the same steroids (0.3 mg EB + 3.0 mg P4) at 1 or 2 days old. At 3 months old, the rats were ovariectomized, chemically stimulated to exhibit estrus behaviors using a standard protocol and tested for receptivity to proven male rats. Untreated control rats showed normal receptivity (i.e., lordosis) and allowed males to mate. However, rats treated with EB+P4 did not exhibit lordosis or allow mating. These results indicate that the combined use of estrogen and progesterone could be an effective non-surgical method for inhibiting mating behavior and, consequently, neutralizing female dog reproduction.

  PublisherDOI

• Conditional ablation of <i>Insr</i> and <i>Igf1r</i> using <i>Esr2</i> -Cre leads to abnormal ovarian follicle development and infertility in mice

  Biology of Reproduction · 2025-08-06

  articleOpen access

  Conditional ablation of Igf1r in early folliculogenesis has demonstrated the necessity of insulin signaling to progress to the antral stage, whereas ablation of both Insr and Igfr1 in the periovulatory window allows the formation of the antrum but reduces the efficiency of ovulation and subsequent luteinization. For this study, we examined the independent and shared actions in single and double knockouts (DKO) for Insr and Ifg1r using Esr2-Cre. As this recombinase is active during neonatal ovarian development and the initial wave of folliculogenesis, we hypothesized that abnormalities in ovary formation and establishment of the initial follicle pool would occur, which could alter female reproductive lifespan. We found that ablation of both receptors led to a delay in puberty, altered mating frequency, and ultimately infertility for Igf1rd/d and DKO females. Quantitation of germ cell cyst breakdown, and formation of primordial and primary follicles were normal in the neonatal window and at puberty, suggesting insulin signaling was not essential for establishment of ovarian reserve. However, the loss of IGF1R signaling impaired transition from primary to secondary follicles, which was worsened when IGF ligand cross-reactivity from INSR signaling was lost in DKO mice. DKO mice also exhibited abnormal follicle activation in the absence of hormone stimulation, but no subsequent proliferation of granulosa cells or antrum formation occurred. In adult mice, loss of either receptor disrupted estrous cyclicity, with DKO mice rarely leaving metestrus indicating abnormal regulation of the HPG axis contributing to subfertility and infertility observed in single and double receptor knockouts.

  PublisherOA PDFDOI

• MON-159 A Critical Role of an ESR2-to-ESR1 Switch in the Female Reproductive Axis

  Journal of the Endocrine Society · 2025-10-01

  articleOpen accessSenior author

  Abstract Disclosure: M.A. Bunnell: None. P.P. Lin: None. J. Oh: None. C. Park: None. S. Zhou: None. C.J. Ko: None. Most actions of estradiol (E2) are exerted by two distinct nuclear receptors, estrogen receptor alpha (ESR1) and estrogen receptor beta (ESR2). Despite being activated by the same ligand, ESR1 and ESR2 exhibit distinct expression patterns and elicit different physiological outcomes. Typically, ESR1 mediates E2-driven actions in regulating reproductive functions. ESR2 modulates or attenuates these effects. Global ESR1 knockout mice are infertile, underscoring ESR1’s essential role in regulating fertility. In this study, we tested a novel hypothesis that a switch from ESR2 to ESR1 in specific cell lineages is critical for female fertility and health. To test this, we generated a transgenic mouse model in which ESR1 expression is specifically ablated in the ESR2-expressing cell lineage using the Cre-LoxP system (Esr1 flox/flox Esr2 iCre/WT; Esr2-Esr1KO). Female Esr2-Esr1KO mice did not produce any litters (0% vs. 100% in WT controls; p &amp;lt; 0.0001) when paired with proven male breeders. Their ovaries were smaller than WT, and had follicular cysts, disrupted cumulus oocyte complexes, atretic follicles, and lacked corpus luteum (CL), indicating impaired folliculogenesis and ovulation. These ovarian phenotypes were indicatives of an inadequate supply of gonadotropins. To determine if the GnRH-gonadotroph axis was impaired in the Esr2-Esr1KO mice, we measured LH secretion before and 30 minutes after kisspeptin (KP-10, 50 nmol) stimulation in adult female mice. WT mice exhibited a significant increase in LH concentration (0.88 to 2.88 ng/mL, p=0.003), whereas Esr2-Esr1KO mice did not (0.37 to 0.35 ng/mL, p=0.9), indicating an impaired GnRH-gonadotroph axis. Thus, inadequate LH secretion contributed to the anovulatory phenotype in the ovaries of Esr2-Esr1KO mice. To determine ovarian responsiveness to gonadotropins, mice were treated with gonadotropins following the superovulation protocol. Although fewer than WT, Esr2-Esr1KO mice ovulated oocytes (p =0.0008) and formed CL, suggesting that follicular atresia was primarily caused by an inadequate supply of endogenous gonadotropins. In conclusion, ESR1 deletion in ESR2-expressing lineages results in female infertility due to impaired gonadotropin secretion, revealing a previously unknown requirement for ESR2-to-ESR1 switch in the hypothalamic-pituitary-ovarian axis. These findings highlight the significance of estrogen receptor plasticity in reproductive organs and their functions. Presentation: Monday, July 14, 2025

  PublisherOA PDFDOI

• A Dynamic Shift in Estrogen Receptor Expression During Granulosa Cell Differentiation in the Ovary

  Endocrinology · 2025-01-06 · 6 citations

  articleOpen accessSenior author

  This study uncovers a dynamic shift in estrogen receptor expression during granulosa cell (GC) differentiation in the ovary, highlighting a transition from estrogen receptor alpha (ESR1) to estrogen receptor beta (ESR2). Using a transgenic mouse model with Esr1-iCre-mediated Esr2 deletion, we demonstrate that ESR2 expression is absent in GCs derived from ESR1-expressing ovarian surface epithelium (OSE) cells. Single-cell analysis of the OSE-GC lineage reveals a developmental trajectory from Esr1-expressing OSE cells to Foxl2-expressing pre-GCs, culminating in GCs exclusively expressing Esr2. Transcriptome analyses identified vasculature-derived TGFβ1 ligands as key regulators of this transition. Supporting this, TGFβ1 treatment of cultured embryonic ovaries reduced Esr1 expression while promoting Esr2 expression. This study underscores the capability of GCs to switch from ESR1 to ESR2 expression as a fundamental aspect of normal differentiation.

  PublisherOA PDFDOI

• SUN-152 Neonatal Exposure to Estrogen Impairs Intra-ovarian Ovulatory Machinery

  Journal of the Endocrine Society · 2025-10-01

  articleOpen accessSenior author

  Abstract Disclosure: J. Oh: None. C. Park: None. P. Lin: None. S. Zhou: None. C. Ko: None. Endocrine-disrupting chemicals (EDCs) with estrogenic properties are pervasive in the environment, interfering with hormonal signaling pathways and causing long-term reproductive dysfunction. Neonatal exposuse to estrogenic EDCs has been linked to ovarian abnormalties and impaired fertility, yet the underlying mechanisms remain poorly. We recently observed that adult rats neonatally exposed to estradiol for an extended period exhibit a complete lack of corpus lutea (CL), indicating ovulatory failure. This study investigates the hypothesis that prolonged neonatal exposure to an estrogenic EDC disrupts the establishment of the intra-ovarian ovulation machinery. To test the hypothesis, 1-day-old female pups female rats were treated with estradiol benzoate (EB, 0.3mg)-containing microspheres to that were designed to release the EB for 2 weeks. We examined their ovaries on days 7 and 14 by histology. To assess their ovulatory capacity, superovulation was induced at a prepubertal age (23 days) and at an adult age (2 months). The oocytes were collected from oviducts at 16 hours (h) post-hCG injection for oocyte counting, and ovaries were collected at 6 h after hCG injection for gene expression analysis and histology. Histology revealed delayed foliculogenesis the neonatally exposed to estrogen (NeoEE) rats. On day 7, ovaries of NeoEE rats exhibited incomplete germ cell nest breakdown, which was resolved by day 14, indicating delayed follicular development. Superovulation at an adulthood failed to produce oocytes in NeoEE rats, whereas Control rats released an average of 39 oocytes/rat (p&amp;lt;0.001). Ovarian histology showed that NeoEE rats contained numerous cystic follicles but no CL, indicating impaired ovulation rather than foliculogenesis impairment. Further anylsis of immature NeoEE ovaries at 6 h after hCG injection reveald dysregulated expression of genes essential for successful ovulation - endothelin-2 (Edn2), progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2). These results suggest impaired contraction and inflammatory required for ovulation. Taken together, these results show that early-life estrogen exposure causes disruption of ovulatory machinery, providing mechanistic insignt into how EDC exerts long-term adverse effects on female reproductive health. Presentation: Sunday, July 13, 2025

  PublisherOA PDFDOI

• Granulosa cell expression of <i>Fos</i> is critical for regulating ovulatory gene expressions in the mouse ovary

  The FASEB Journal · 2025-02-13 · 2 citations

  articleOpen access

  Abstract A previous study showed that female Fos null mice fail to ovulate even when given gonadotropins, suggesting that ovarian expression of Fos is critical for successful ovulation. However, the expression of FOS and function of FOS have not been determined in the mouse ovary. FOS, a member of the Fos family ( Fos, Fosb, Fosl1 , and Fosl2 ), functions as a transcription factor by forming a heterodimer complex with a member of Jun family ( Jun, Junb , and Jund ). This study demonstrated rapid increases in Fos , along with other Fos and Jun family members, after hCG administration in the ovary of immature PMSG‐primed mice and after the LH surge in naturally cycling animals. ChIP‐seq analysis identified 1965 FOS‐binding genes in granulosa cells collected at 3 h post‐hCG, including Pgr , Ptgs2, Tnfiap6 , and Edn2 , genes known to be involved in the ovulatory process. When super‐ovulation was induced, the number of oocytes released was significantly reduced in Esr2 cre/+ ‐driven granulosa cell‐specific Fos knockout ( gcFos KO) mice. This reduction was accompanied by lower expressions of Pgr, Ptgs2, Ptgs1, and Edn2 in preovulatory follicles of gcFosKO mice compared to those in control littermates. In addition, gcFos KO mice showed a trend toward a decreased average litter size. Together, the present study indicates that the preovulatory induction of Fos expression is crucial for increasing the expression of key ovulatory genes, yet the role of FOS may be partially substituted by other Fos and Jun family members induced in the preovulatory follicle in the gcFos KO mouse ovary.

  PublisherOA PDFDOI

• PTBP1 mediates Sertoli cell actin cytoskeleton organization by regulating alternative splicing of actin regulators

  Nucleic Acids Research · 2024-10-07 · 9 citations

  articleOpen access

  Spermatogenesis is a biological process within the testis that produces haploid spermatozoa for the continuity of species. Sertoli cells are somatic cells in the seminiferous epithelium that orchestrate spermatogenesis. Cyclic reorganization of the Sertoli cell actin cytoskeleton is vital for spermatogenesis, but the underlying mechanism remains largely unclear. Here, we report that the RNA-binding protein PTBP1 controls Sertoli cell actin cytoskeleton reorganization by programming alternative splicing of actin cytoskeleton regulators. This splicing control enables ectoplasmic specializations, the actin-based adhesion junctions, to maintain the blood-testis barrier and support spermatid transport and transformation. Particularly, we show that PTBP1 promotes actin bundle formation by repressing the inclusion of exon 14 of Tnik, a kinase present at the ectoplasmic specialization. Our results thus reveal a novel mechanism wherein Sertoli cell actin cytoskeleton dynamics are controlled post-transcriptionally by utilizing functionally distinct isoforms of actin regulatory proteins, and PTBP1 is a critical regulatory factor in generating such isoforms.

  PublisherDOI

• A Novel, Humane Method of Sterilizing Dogs, Cats, and Pigs

  American Journal of Veterinary Research · 2024-10-11

  articleOpen access1st authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R01HD052694

  NIH · $1.2M · 2012

• Conversion of ERalpha cells to ERbeta cells in a cell lineage

  NIH · $436k · 2018–2021

• Angiogenesis in the Primate Ovulatory Follicle

  NIH · $12.1M · 2021

Frequent coauthors

• Radwa Barakat

  35 shared

• Rex A. Hess

  University of Illinois Urbana-Champaign

  23 shared

• Phillip J. Bridges

  University of Kentucky

  21 shared

• Yongbum Koo

  Inje University

  17 shared

• Chan Jin Park

  University of Illinois Urbana-Champaign

  14 shared

• Jodi A. Flaws

  University of Illinois Urbana-Champaign

  14 shared

• Joseph A. Cacioppo

  Alta Bates Summit Medical Center

  13 shared

• Po-Ching Lin

  University of Illinois Urbana-Champaign

  12 shared

Education

• Ph.D, Biology Education

  Seoul National University

  1998