The female fertility squad and their hormonal magic
Thecal cells are found in the follicles of mammals, where they are essential for various aspects of female physiology. They originate within secondary follicles and differentiate into two main types: theca interna and theca externa. The theca interna contains vascular endothelial cells and immune cells, while the theca externa is mainly made up of fibroblast-like cells (1). One key role of the theca interna is participating in steroidogenesis, which means it helps convert cholesterol into steroid hormones such as androgens. The full function of theca externa is still not well understood. Overall, thecal cells are important because they provide structural support for the follicle and produce androgens, which are used by neighbouring granulosa cells to create estradiol, a hormone vital for reproduction. Thecal cells are well-differentiated and display structural traits typical of steroid-producing cells, such as numerous mitochondria with vesicular cristae, a smooth endoplasmic reticulum, and lipid droplets (2). Understanding the characteristics and development of thecal cells is crucial for grasping how ovarian follicles function and how female fertility is regulated throughout reproductive life.
Life span of thecal cells
The lifespan of thecal cells is closely linked to the overall dynamics of the process of folliculogenesis (maturation of the ovarian follicle). The growth and development of the follicle is a lengthy process and may require almost a year for the primordial follicle to reach the ovulatory stage (3). The two major terminal processes of the mature theca cells present in the follicles are atresia and ovulation. During atresia, follicles undergo degeneration without the release of an oocyte (4), whereas in ovulation, the follicles reach maturity and rupture to release an oocyte in the fallopian tube (5). Atresia is a fundamental process in ovarian follicles that is intrinsically connected to the cell’s natural cell death. This process happens in different cell types and can occur in various ways, including apoptosis, autophagy, necrosis, and cornification. Thecal cells appear to be especially susceptible to cell death early in follicular development, and extensive hypertrophy of these cells has been documented during atresia in humans, rats, and rabbits (2). In this terminal process, thecal cells exhibit more fibroblast-like characteristics along with diminished capability of androgen production (6). Depending on the fate of antral follicles, the terminal forms of theca cells are likely to differ. Maximum luteinization followed by apoptotic disappearance is observed in theca interna cells of ovulating follicles, whereas hypertrophied and hormonally inert fibrocytes are prominent in theca cells of atretic follicles (7).
Importance of Thecal Cells in Reproductive Health
Thecal cells are essential for proper ovarian function, directly shaping fertility and menstrual cycle regulation. Their primary role is the synthesis of androgens under stimulation from luteinizing hormone (LH), which are then converted by granulosa cells into estrogens through aromatase. This androgen–estrogen interplay is fundamental for follicle maturation, ovulation, and preparation of the endometrium for implantation (8). Beyond steroidogenesis, thecal cells also secrete growth factors and cytokines that govern follicle growth and angiogenesis while coordinating with granulosa cells to ensure synchronized follicular development. Disruption of thecal cell function can result in hormonal imbalance and reproductive disorders such as polycystic ovary syndrome (PCOS) or anovulation (9). 3D thecal cell models are beneficial in organoid development, enabling the creation of native microenvironments that mimic in vitro fertilisation efficacy, thereby facilitating personalised medicine and cell-based therapies for ovarian dysfunction (10). Despite their indirect roles, by contributing to both the structural and endocrine functions of the ovarian follicle, thecal cells are indispensable regulators of female reproductive health, and thus represent critical targets for advancing fertility research and therapeutic strategies.
Recognizing and appreciating the labs working in this space
- Astapova Lab, University of Rochester Medical Center. Rochester, New York, USA. https://www.urmc.rochester.edu/labs/astapova
- Woodruff Lab, East Lansing, Michigan, USA. https://woodrufflab.org/
- Reproductive Endocrinology Lab , Weill Cornell Medicine, New York, USA. https://reproendolab.weill.cornell.edu/team/daylon-james X: @WeillCornell
- Janette McAllister, Penn State College of Medicine, Pennsylvania, USA. https://pure.psu.edu/en/persons/janette-mcallister Instagram: @pennstatecollegeofmedicine
- Clark Lab, University of California, Los Angeles, USA. https://clark.mcdb.ucla.edu/ , X: @clarklabucla1
- Dr. Andrea Cupp’s Lab, University of Nebraska-Lincoln, Nebraska, USA. https://animalscience.unl.edu/research/research-areas/physiology-research/dr-andrea-cupps-laboratory/ , X: @UNL_AniSci
- Elisabet Stener-Victorin’s research group, Karolinska Institute, Stockholm, Sweden. https://morgridge.org/profile/james-thomson/ , Bluesky: @ki.se
- The Curry Lab, University of Kentucky College of Medicine, Kentucky, USA. https://medicine.uky.edu/departments/obgyn/curry-lab , X: @UKYMedicine
- Francisco Diaz Lab, Department of Animal Science, Penn State College of Agricultural Studies, Pennsylvania, USA. https://animalscience.psu.edu/research/labs/diaz
References
- Liu, T., Qin, Q. Y., Qu, J. X., Wang, H. Y., & Yan, J. (2020). Where are the theca cells from: the mechanism of theca cells derivation and differentiation. Chinese medical journal, 133(14), 1711–1718. https://doi.org/10.1097/CM9.0000000000000850
- Young, J. M., & McNeilly, A. S. (2010). Theca: the forgotten cell of the ovarian follicle. Reproduction (Cambridge, England), 140(4), 489–504. https://doi.org/10.1530/REP-10-0094
- Williams CJ, Erickson GF. Morphology and Physiology of the Ovary. [Updated 2012 Jan 30]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK278951/
- Zhou, J., Peng, X., & Mei, S. (2019). Autophagy in Ovarian Follicular Development and Atresia. International journal of biological sciences, 15(4), 726–737. https://doi.org/10.7150/ijbs.30369
- Holesh JE, Bass AN, Lord M. Physiology, Ovulation. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441996/
- Hsueh, A. J., Billig, H., & Tsafriri, A. (1994). Ovarian follicle atresia: a hormonally controlled apoptotic process. Endocrine reviews, 15(6), 707–724. https://doi.org/10.1210/edrv-15-6-707
- Tajima, K., Orisaka, M., Mori, T., & Kotsuji, F. (2007). Ovarian theca cells in follicular function. Reproductive biomedicine online, 15(5), 591–609. https://doi.org/10.1016/s1472-6483(10)60392-6
- Reed BG, Carr BR. The Normal Menstrual Cycle and the Control of Ovulation. [Updated 2018 Aug 5]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/sites/books/NBK279054/
- Jozkowiak, M., Piotrowska-Kempisty, H., Kobylarek, D., Gorska, N., Mozdziak, P., Kempisty, B., Rachon, D., & Spaczynski, R. Z. (2022). Endocrine Disrupting Chemicals in Polycystic Ovary Syndrome: The Relevant Role of the Theca and Granulosa Cells in the Pathogenesis of the Ovarian Dysfunction. Cells, 12(1), 174. https://doi.org/10.3390/cells12010174
- Del Valle, J. S., & Chuva de Sousa Lopes, S. M. (2023). Bioengineered 3D Ovarian Models as Paramount Technology for Female Health Management and Reproduction. Bioengineering (Basel, Switzerland), 10(7), 832. https://doi.org/10.3390/bioengineering10070832
About the author:
DR. SURUCHI PODDAR
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Poddar received a PhD in Biomedical Engineering from Indian Institute of Technology-Banaras Hindu University (IIT-BHU), Varanasi, India. She started her career as a postdoctoral researcher in 2020 with the Nanoscience Technology Center at the University of Central Florida, Orlando where she worked on a multi-organ human-on-a-chip system. Currently she is working on solid-state nanopore technology at Wake Forest University, North Carolina. When not working, she enjoys watching movies, cooking food and exploring new places, restaurants, attractions.
About the artists:
OLGA KURKINA
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
My passion for art and love for medicine led me to the field of medical illustration, a profession in which I have been dedicated for many years. Through my work, I have the privilege of meeting and collaborating with remarkable individuals — doctors and scientists who are at the forefront of global scientific advancements. Their dedication and discoveries continue to inspire me. As a medical illustrator at a medical communications agency, my primary role is to transform complex processes and concepts into visually appealing and easily understandable images that become part of an animation or publication. Additionally, my works have been featured in numerous scientific magazines and books. Now I live and work in Poland.
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DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
