Jackson Sapuleni: How does early-life weight gain affect female fertility?

Jackson Sapuleni PhD’28 is a doctoral student working in the lab of Yi Athena Ren, associate professor of reproductive biology. Jackson’s research focuses on the effect of early-life weight gain on the ovary.

We spoke with Jackson about his research and the impact weight gain can have on ovarian development and function.

What does excessive weight gain early in life do to the ovaries?

Weight gain, especially when it leads to an increase in body fat, has a direct impact on how the ovaries function because body fat is not just a passive storage of energy. It actively produces hormones and other signaling molecules. As body fat increases, it alters the balance of important hormones, such as insulin and estrogen, as well as inflammatory signals in the body.

The ovary relies on a very precise hormonal environment to function properly, so even small disruptions in these signals can interfere with its normal role. When these hormonal changes occur, the ovary may struggle to release eggs regularly. This can lead to irregular or missed menstrual cycles. In addition, the environment within the ovary can become less supportive for healthy follicle development, which may reduce fertility.

Weight gain can also lead to increased inflammation and physical changes within the ovarian tissue itself. The ovary may become stiffer and less flexible, which can interfere with how follicles grow and mature. Follicles constitute the environment where eggs grow. So when this environment is less optimal or even detrimental due to obesity and inflammation, even if eggs can mature and be released to fertilize during ovulation, they can be of low quality and lead to defective growth of embryos.

a man looks through a microscope — In the Ren lab, Sapuleni looks at an ovarian section to assess how collagen deposition is distributed in different ovarian compartments. Photo by Jackie Swift.

A key part of your research involves the extracellular matrix, where a lot of organizational changes are happening during the neonatal period. Can you explain what the ECM is and why it matters in the ovary?

The extracellular matrix (ECM) is the supporting scaffold that surrounds cells in a tissue. It provides structural support while also regulating cell communication growth and migration. You can think of it like the framework of a building. It holds everything in place, but it also does much more than that in regulating cell function.

In the ovary, the ECM plays a similar role in providing physical support for developing follicles, which contain eggs. It also helps control how cells grow, communicate and survive. One of the most important things it does is to influence how stiff or soft the tissue is, and it is constantly remodeling to adapt to the changing needs of the growing follicles in the ovary. This can determine the growth and function of cells. If the ECM becomes too stiff or improperly organized, it can disrupt normal follicle development, which may affect fertility.

Your research looks at overnutrition very early in life. How does this affect fertility later?

This idea comes from a concept called the Developmental Origins of Health and Disease, which simply means that what we are exposed to early in life, before and just after birth, can “program” how our bodies work in adulthood. During this time, organs are still developing, so they are especially sensitive to changes in nutrition and environment. Because of this, even small imbalances or disruption early on can have long-lasting effects.

I focus on the neonatal period, which is the time just after birth, because this is when the ovary is going through some of its most important steps in the mouse models we use. During this window, immature egg cells are being organized into follicles, which are essential for fertility later in life. If something disrupts this stage, it can affect reproductive health long into adulthood.

a man and a woman look at an image of cells on a computer screen — Sapuleni and fellow graduate student Justine Galliou discuss the ways that overfeeding may affect follicle size. Photo by Jackie Swift.

How are you carrying out your study?

I use a mouse model where some pups are raised in smaller litters of three as compared to normal litters that are normally more than eight. With fewer siblings, each pup gets more milk, which mimics early-life overfeeding. I then compare these mice to those raised in normal litter sizes. This allows me to understand how excess nutrition during this critical early period affects ovarian development.

I’m investigating whether early-life overfeeding changes the structure of the ECM. I use imaging techniques to look at how collagen, the main structural component of the ECM, is arranged in the ovary. I also measure how stiff or soft the tissue is, because this can influence how cells behave. I then examine the genes that are involved in building and modifying this structure to see if they are altered.

The goal of my research is to understand whether too much nutrition early in life makes the ovarian environment less optimal, perhaps too stiff or disorganized, which could interfere with normal development. This could help explain why early life conditions can have lasting effects on fertility and reproductive health.

Looking forward, what are the next steps?

I’m currently drafting a manuscript to show the findings of this study. I also presented the data from this work at the Tri Repro Symposium earlier this May, and I'll be presenting again at the Society of Reproduction conference in July. We also still have some interesting work to do to test whether these changes can be reversed or prevented and really assess how they can affect long term reproductive health.

Jackie Swift is the communications specialist for the Cornell CALS Department of Animal Science.