About

Nataki Douglas, PHD, MD, is an Associate Professor and the Director of Reproductive Endocrinology and Infertility at Rutgers New Jersey Medical School. She is part of the Department of Obstetrics, Gynecology and Women's Health within the Center for Immunity and Inflammation. Dr. Douglas completed her PhD and MD at Yale University in 2002 and earned her BA from Cornell University in 1993. Her research focuses on reproductive endocrinology and infertility, contributing to the understanding of immune and inflammatory processes related to reproductive health. She is actively involved in clinical practice at University Hospital, Newark, and participates in various insurance networks. Her professional profile and publications are accessible through the Center for Immunity & Inflammation and the Institute for Infectious & Inflammatory Diseases.

Research topics

• Endocrinology
• Medicine
• Internal medicine
• Obstetrics
• Gynecology

Selected publications

• Hormonal stimulation induces broader decidualization responses than cAMP alone in 3D human endometrial organoids

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-28

  articleOpen access

  Abstract The human endometrium undergoes cyclic, hormone-driven remodeling that establishes a transient window of receptivity required for embryo implantation, placentation, and maintenance of pregnancy. Decidualization of endometrial stromal cells is a central component of this process and can be induced in vitro using cAMP alone or in combination with ovarian steroid hormones (EPC: estradiol, progesterone, and cAMP). Although cAMP activates the core decidual transcriptional program, whether hormone supplementation induces a more physiologically relevant response remains unclear, particularly in 3D endometrial organoid (Endo-organoid) models which have emerged as a new alternative methodology (NAM). Here, we compared morphological and transcriptomic responses of human endometrial stromal cell-derived Endo-organoids undergoing decidualization induced by cAMP or EPC stimulation. EPC-treated Endo-organoids exhibited enhanced structural remodeling and more advanced morphological transformation compared with cAMP-treated organoids. RNA-seq analysis revealed substantial overlap in canonical decidual gene expression between the two conditions, but EPC induced broader transcriptional and pathway-level changes, including enrichment of metabolic, stress-response, and differentiation-related processes. Together, these findings demonstrate that while cAMP activates the core decidual program, EPC elicits a broader and more physiologically relevant decidualization response in 3D human Endo-organoids, providing guidance for optimizing Endo-organoids to study endometrial receptivity, implantation, and early pregnancy success.

  PublisherOA PDFDOI

• Single-cell mapping of human endometrium and decidua reveals epithelial and stromal contributions to fertility

  JCI Insight · 2026-01-22 · 1 citations

  articleOpen accessSenior author

  The human endometrium undergoes dynamic changes across the menstrual cycle to establish a receptive state for embryo implantation. Using bulk and single-cell RNA-Seq, we characterized gene expression dynamics in the cycling endometrium and the decidua from early pregnancy. We demonstrated that during the mid-secretory phase - the period encompassing the window of implantation - secretory glandular epithelial cells undergo notable transcriptional changes and alterations in cell-cell communication. Through comprehensive analyses, we identified the glandular epithelium receptivity module (GERM) signature, comprising 556 genes associated with endometrial receptivity. This GERM signature was consistently perturbed across datasets of endometrial samples from women with impaired fertility, validating its relevance as a marker of receptivity. In addition to epithelial changes, we observed shifts in stromal cell populations, notably involving decidual and senescent subsets, which also play key roles in modulating implantation. Together, these findings provide a high-resolution transcriptomic atlas of the receptive and early pregnant endometrium and shed light on key molecular pathways underlying successful implantation.

  PublisherDOI

• Role of KIT signaling in ovarian development and function: insights from multisystem biology

  Biology of Reproduction · 2026-03-12

  articleOpen access

  KIT signaling is a fundamental regulatory pathway that preserves cellular homeostasis and controls cell development and fate across a wide range of organs and cell types. Consistent with this pleiotropic role, mutations in c-KIT/Kit have been associated with a wide range of phenotypes, including sterility, piebaldism, nevus formation, mastocytosis, and multiple malignancies. The contribution of c-KIT/Kit to reproductive function has attracted sustained attention for several decades, underscoring its essential role in fertility and gonadal biology. KIT expression is observed in oocytes - localized to the oocyte membrane and the cytoplasm - as well as in theca cells and interstitial cells, suggesting a multifaceted role in follicular development. Notably, all Kit mutant models develop primary ovarian insufficiency (POI) with variable onset, characterized by endocrine dysfunction, impaired folliculogenesis, and eventual female infertility. These findings collectively establish KIT signaling as a critical regulator of ovarian integrity, as both gain- or loss-of-function mutations in Kit consistently recapitulate POI-associated phenotypes. However, despite substantial progress, the precise molecular mechanisms by which KIT signaling integrates these pathways to preserve primordial follicle survival and prevent POI remain incompletely understood. Here, we summarize current knowledge of KIT expression and the functional consequences of Kit mutations, with particular emphasis on oocytes across ovarian cell populations and in comparison to other organ systems in humans and mice. We further evaluate the physiological and pathological significance of ovarian KIT signaling in female fertility and highlight crucial knowledge gaps that must be addressed to fully elucidate its role in maintaining ovarian function.

  PublisherOA PDFDOI

• Signaling via retinoic acid receptors mediates decidual angiogenesis in mice and human stromal cell decidualization

  The FASEB Journal · 2025-01-07 · 4 citations

  articleOpen accessSenior authorCorresponding

  At the maternal-fetal interface, tightly regulated levels of retinoic acid (RA), the physiologically active metabolite of vitamin A, are required for embryo implantation and pregnancy success. Herein, we utilize mouse models, primary human cells, and pharmacological tools to demonstrate how depletion of RA signaling via RA receptor (RAR) disrupts implantation and progression of early pregnancy. To inhibit RAR signaling during early pregnancy, BMS493, an inverse pan-RAR agonist that prevents RA-induced differentiation, was administered to pregnant mice during the peri-implantation period. Attenuation of RA/RAR signaling prior to embryo implantation results in implantation failure, whereas attenuation of RA/RAR signaling after embryo implantation disrupts the post-implantation decidual vasculature and results in pregnancy failure by mid-gestation. To inhibit RAR signaling during human endometrial stromal cell (HESC) decidualization, primary HESCs and decidualized primary HESCs were transfected with silencing RNA specific for human RARA. Inhibition of RA/RARA signaling prevents initiation of HESC decidualization, but not maintenance of the decidualized HESC phenotype. These data show that RA/RAR signaling is required for maintenance of the decidual vasculature that supports early pregnancy in mice, and distinct RAR signaling is required for initiation, but not maintenance of primary HESC decidualization in vitro.

  PublisherOA PDFDOI

• Freezing first: insights from 8 years of planned oocyte cryopreservation at an “egg freezing clinic”

  Fertility and Sterility · 2025-12-05 · 1 citations

  articleOpen accessSenior author

  OBJECTIVE: To assess the outcomes of oocyte warming (OW) and embryo transfer in individuals who underwent planned oocyte cryopreservation (OC). DESIGN: Retrospective cohort study. SUBJECTS: This study includes all planned OC cycles performed at Extend Fertility before December 31, 2023, and subsequent OW cycles performed before August 2024. EXPOSURE: Age at the time of OC and number of metaphase (M)II oocytes warmed. MAIN OUTCOME MEASURES: The primary outcome was cumulative ongoing pregnancy/live birth (OP/LB) rate per OW cycle, stratified by age and number of MII oocytes warmed. Secondary outcomes included OW survival and fertilization rates and the number of euploid embryos per MII oocyte, categorized by age at the time of OC. RESULTS: Between 2016 and 2023, 4,659 OC cycles were completed for 3,138 patients, with the mean OC start age decreasing from 36.9 ± 2.8 years at the onset to 35.0 ± 3.5 years in the final year of the study. The mean length of time between OC and first OW was 3.4 ± 1.9 years. The mean age at first OW was 39.9 ± 3.5 years, with a median (interquartile range) of 40 (39, 42) years. Among patients who had completed at least one OC cycle before 2020 (n = 2,163), allowing for a minimum follow-up period of 4 years, 10.4% (n = 226) returned for OW. Across 271 OW cycles, the mean number of MII oocytes warmed was 15, with survival and fertilization rates of 90.7% and 77.2%, respectively. Among patients who underwent OC at ≤40 years of age, warming a higher number of MII oocytes was associated with increased euploid embryo yield. The cumulative ongoing pregnancy/live birth rate (OP/LB) rate for the cohort was 70.3%, ranging from 58.3% for 1-9 MII oocytes warmed to 81.8% for >20 MII oocytes warmed. CONCLUSION: Driven by increased awareness and access, patients are undergoing planned OC at younger ages. This study demonstrates high success rates achieved at an "egg freezing clinic", especially among patients who pursue OC at younger ages. It also establishes a framework to estimate the number of euploid embryos from MII oocytes, as well as the likelihood of live birth, stratified by age at OC.

  PublisherDOI

• Non-canonical Notch signaling and gamma secretase inhibitors as potential mechanisms to overcome immunotherapy resistance

  Gynecologic Oncology · 2025-09-01

  articleSenior author
  PublisherDOI

• Utility of ai technology to identify sonographic features of endometrium predictive of cycle outcomes: a pilot study

  Fertility and Sterility · 2025-12-01

  article
  PublisherDOI

• Dynamic expression of endometrial adhesion G protein-coupled receptors during the menstrual cycle and early mouse pregnancy: modulation by ovarian stimulation

  F&S Science · 2025-05-16 · 2 citations

  articleOpen accessSenior author

  OBJECTIVE: To characterize the expression of adhesion G protein-coupled receptors (ADGR) in the human endometrium and early mouse pregnancy. DESIGN: An in silico analysis was performed using a retrospective data set comprised endometrial samples across normo-ovulatory menstrual cycles. Gene expression was then validated using quantitative reverse transcription polymerase chain reaction and mRNA sequencing (mRNA-seq) in prospectively collected endometrial biopsies in the periovulatory and midsecretory stages of natural cycles. Gene expression was also investigated under ovarian stimulation (OS) conditions using mRNA-seq. Early pregnancy mouse models were used to investigate whether trends of dynamic ADGR expression are also conserved in the mouse. SUBJECTS: Twenty-four women aged 21-42 years. EXPOSURE: Ovulatory menstrual cycle or OS cycle. MAIN OUTCOME MEASURES: Gene expression in endometrial biopsies and pregnant mouse uterus. RESULTS: Fifteen women, aged 21-33 years, were recruited in natural cycles during the proliferative phase (cycle days 10-13; n = 4), periovulatory (luteinizing hormone + 12-24 hours; n = 6) period, and midsecretory (luteinizing hormone + 8-9 days; n = 5) phase. Nine women aged 31-42 years old undergoing in vitro fertilization (without fresh embryo transfer) or oocyte cryopreservation using a gonadotropin releasing hormone antagonist protocol were recruited for the OS cohort in either the periovulatory phase (human chorionic gonadotropin + 2; n = 5) or midsecretory phase (human chorionic gonadotropin + 9; n = 4). The in silico analysis revealed dynamic expression for many ADGRs across the menstrual cycle. Differential gene expression was also seen in the prospective analysis within the menstrual cycle phases and between natural cycle and OS conditions. Within early mouse pregnancy, expression was also found to be altered across several Adgr subfamilies. CONCLUSION: The differential gene expression observed between the proliferative and secretory phases of the menstrual cycle, along with changes in expression seen in OS and early mouse pregnancy suggest that ADGR expression is hormonally regulated by estradiol and progesterone.

  PublisherDOI

• Single cell mapping of the human endometrium and first trimester decidua identifies distinct epithelial and stromal cell contributions to fertility

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-04-26 · 1 citations

  preprintOpen accessSenior authorCorresponding

  Abstract The human endometrium undergoes dynamic changes across the menstrual cycle to establish a receptive state for embryo implantation. Using bulk and single-cell RNA sequencing, we characterized gene expression dynamics in the cycling endometrium and the decidua from early pregnancy. We are the first to demonstrate that during the mid-secretory phase—the period encompassing the window of implantation—secretory glandular epithelial cells undergo notable transcriptional changes in cell-cell communication. Through comprehensive analyses, we identified the Glandular Epithelium Receptivity Module (GERM) signature, comprising 556 genes associated with endometrial receptivity. This GERM signature was consistently perturbed across multiple datasets of endometrial samples from women with impaired fertility, validating its relevance as a marker of receptivity. In addition to epithelial changes, we observed shifts in stromal cell populations, notably involving decidual and senescent subsets, which also play key roles in modulating implantation. Together, these findings provide a high-resolution transcriptomic atlas of the receptive and early pregnant endometrium and shed light on key molecular pathways underlying successful implantation.

  PublisherOA PDFDOI

• Exposure to Long- and Short-Chain Per- and Polyfluoroalkyl Substances in Mice and Ovarian-Related Outcomes: An <i>in Vivo</i> and <i>in Vitro</i> Study

  Environmental Health Perspectives · 2025-04-07 · 20 citations

  articleOpen access

  BACKGROUND: The extensive use of per- and polyfluoroalkyl substances (PFAS) has led to environmental contamination and bioaccumulation of these substances. Previous research linked PFAS exposure to female reproductive disorders, but the mechanism remains elusive. Further, most studies focused on legacy long-chain PFOA and PFOS, yet the reproductive impacts of other long-chain PFAS and short-chain alternatives are rarely explored. OBJECTIVES: We investigated the effects of long- and short-chain PFAS on the mouse ovary and further evaluated the toxic mechanisms of long-chain perfluorononanoic acid (PFNA). METHODS: mouse exposure model to verify the accumulation of PFNA in the ovary and its ovarian-disrupting effects. RESULTS: extrapolation analyses estimated follicular rupture as the most sensitive end point and that observed effects occurred in the range of human exposure to long-chain PFAS. DISCUSSION: agonist in granulosa cells to interfere with gonadotropin-dependent follicle growth, hormone secretion, and ovulation; and exposure to high levels of PFAS may cause adverse ovarian outcomes. https://doi.org/10.1289/EHP14876.

  PublisherOA PDFDOI

Recent grants

• Innate Immune Mechanisms at the Maternal-Fetal Interface in Normal and Superovulatory Pregnancy

  NIH · $3.8M · 2019–2025

• Role of angiogenic Notch in uterine decidualization and placentation

  NIH · $2.0M · 2016–2021

Frequent coauthors

• Qingshi Zhao

  59 shared

• Sara S. Morelli

  Rutgers, The State University of New Jersey

  52 shared

• Anat Chemerinski

  University Reproductive Associates

  43 shared

• Tracy Wu

  Rutgers, The State University of New Jersey

  41 shared

• Alexander Lemenze

  Rutgers New Jersey Medical School

  39 shared

• Mark H. Einstein

  Rutgers New Jersey Medical School

  39 shared

• Mark V. Sauer

  Rutgers, The State University of New Jersey

  35 shared

• Andy V. Babwah

  Johnson University

  32 shared

Education

• B.A.

  Cornell University

  1993

• M.D.

  Yale University

  2002

• Ph.D.

  Yale University

  2002