Dartmouth-Led Study Advances Understanding of Ovulation for Contraceptive Discovery

Composite image of an ovarian follicle with an oocyte in the center, showing expression of genes (each spot) in cells (stained blue). (Image by Rhea Sharma and Ruixu (Rachel) Huang)

"We used a technology called spatial transcriptomics to build a high-resolution map of what the ovary looks like across ovulation time," said Dartmouth Engineering professor Britt Goods, senior author on the study published today in PLOS Biology. "This technology allows you to look at the genes expressed in every individual cell in order to better understand the biology of ovulation. Because if you don't understand the biology, it makes it really hard to develop any sort of intervention or therapeutic."

The resulting data provides critical information about which cell types are important for driving ovulation, and what genes researchers might target to enable new types of contraceptives. 

"One of the things we found is that there are cells called cumulus cells that are super unique to the ovulating follicle, and we identified two types of these cells," explained Goods. "If we can find a target in cumulus cells, that would be ideal because they're very restricted to the ovary, which makes the chance of negative side effects in other places in the body much lower."

Currently, many women stop taking hormonal birth controls within the first year due to adverse side effects such as irregular bleeding, nausea, headaches, cramping, depression, and weight gain. "Hormonal birth controls, while they're super effective at preventing pregnancy when taken properly, they have this whole array of side effects that make it challenging for people to adhere to them," said Goods. "We want to find non-hormonal contraceptives that allow women to retain their natural hormone cycles."

Barrier methods, such as condoms and diaphragms, are widely available but have higher failure rates and are often found to be obtrusive. "Providing more options that allow the user to have control in a discreet way is important for family planning, particularly globally," continued Goods. "Something that's discreet, that can be taken and then stopped to resume fertility quickly—it has to check all these boxes, which makes developing these methods very challenging." 

Lead authors (l to r) Caroline Kratka of Northwestern U and Ruixu (Rachel) Huang of Dartmouth.

One of the study's lead authors is Ruixu (Rachel) Huang, a PhD student in Professor Goods' lab. "What excites me most is the interdisciplinary nature of this work, where spatial omics and transcriptomics meet computational modeling," said Huang. "As the field advances, we increasingly rely on contributions from diverse disciplines and on technologies like these to drive meaningful discoveries in reproductive biology." 

Goods' team is part of a larger ongoing effort to identify molecular candidates that can be pre-clinically tested to begin to move them through the drug development pipeline. "The group is called the Ovarian Contraceptive Discovery Initiative, OCDI, which is a partnership across four different schools that was funded by the Bill and Melinda Gates Foundation," said Goods. "The goal is to develop enabling technologies and data sets that we can use to identify novel non-hormonal contraceptives. This paper is big part of that initiative."

Participating institutions include Northwestern University, the Broad Institute of MIT and Harvard, and Rutgers University. The group will also be using their new data to investigate reproductive health challenges beyond contraception. "If we can deeply understand what typical ovulation should look like, we can then compare that to cases of infertility," added Goods. "Because if you can prevent pregnancy, if you think about reversing that, maybe you can do something to enhance fertility."

The Goods Lab plans to continue to leverage new technology to expand biological knowledge that leads to novel healthcare solutions. "We're at a point where we have so many technologies that my group is excited to use. And this study is a great example of taking a cutting-edge technology and using it to understand biology so we can unlock things that are useful."