Is full-term childbirth a mystery? He is committed to exploring the secrets hidden in the beginning of life

Pregnancy is called "pregnancy", and raising a child is called "nurturing". Mothers who give birth to children always have a "soft light filter". When people mention their mothers, their tone will unconsciously become gentle, and their eyes will reveal a special emotion and attachment. This is probably because the formation of every living body is inseparable from the mother's reproduction. In other words, to understand the mystery of life, perhaps we have to start from the origin - pregnancy behavior.

▲High Road

In textbooks, pregnancy is the process of embryo and fetus growth and development in the mother's body, starting from the fertilization of mature eggs and ending with the expulsion of the fetus and its appendages from the mother's body. But in the eyes of Gao Lu, a physiologist and director of the Department of Physiology at the Naval Medical University of the Chinese People's Liberation Army, this is far from a process that can be summed up in one word. "Pregnancy is a very complex but extremely coordinated physiological process." He said that in the 10 months when two lives are interdependent and connected to each other, there are too many mysteries that can be deeply explored: "The essence of the fetus is a semi-allogeneic transplant, but why does it not cause the mother's rejection reaction?" "What is the trigger for 'ripening the melon' and starting labor?"... In order to further restore the whole process of human reproduction, reveal scientific truth, help humans deeply understand the origin of life, and also for safe and high-quality pregnancy and promote the development of modern reproductive medicine, he has been on this scientific research road for 20 years since the postgraduate stage.

Inheritance: Determine the profession and path

Beliefs determine the foundation, and flags gather strength. Born under the red flag and raised in a military family, Gao Lu was often attracted by his father's military uniform since he was young, and he had a strong desire to join the army. Although he saw the hardship of his parents' long-term separation, he couldn't suppress his joy and excitement every time he was able to visit his father's military camp during the visiting season. The morning horns and the uniform training sounds in the army sounded like calls to Gao Lu, inspiring him to join the military camp one day. Under the guidance of the "red gene", Gao Lu worked hard in junior high and high school, and resolutely wrote down the names of several military academies on the college entrance examination application form. "To be honest, my test scores were pretty good, which means I had more choices, but I didn't consider other schools. I just wanted to join the army. This is not only to inherit my father's legacy, but also my own interest." As Gao Lu said, his choice came from his heart, so he was extremely determined. Even though his teachers and relatives had kindly reminded him of the hardships he might face in the future, including being away from his family and settling down in the frontier, he still resolutely embarked on this journey of life of armored soldiers and climbing to the top.

Although Gao Lu was attracted by his father's green military uniform, he also had his own ideas - he chose to study at the Naval Medical University of the Chinese People's Liberation Army, vowing to put on a "white battle robe" in addition to the military uniform. "There is no doctor in my family, but I have a natural trust and yearning for the profession of 'doctor' since I was a child. I believe that studying medicine can truly serve the public, save the dying and the wounded, and solve problems. If I can combine the spirit of military service and medical practice - require myself to follow the iron rules of the army, and benefit the world with a benevolent heart, I think this is a great thing. Although I haven't reached this level yet, I will continue to work towards this goal and learn from the predecessors and everyone around me."

After entering the PLA Naval Medical University, Gao Lu fulfilled his promise to himself through his actual performance. He has accumulated profound professional knowledge and cultural heritage in a large number of typical teams of the times, including Wu Mengchao, a "model medical expert", Lv Shicai, a "model military doctor", Li Landing, a "model female medical worker", Kong Xiantao, a "famous teacher who is willing to be a stepping stone for others", and Chen Yizhang, a "true scientist needed by the times". Since he started researching perinatal and reproductive medicine as a graduate student, he has published more than 30 Science Citation Index (SCI) papers as the first or corresponding author, with the highest impact factor of a single paper being 19.456. He has also presided over seven national-level projects, including the National Natural Science Foundation's "Outstanding Young Scientist Fund", key international cooperation projects, and key R&D program projects, as well as more than ten provincial and ministerial-level projects. He has been successfully selected for talent programs such as the "National Outstanding Young Scientist", "Shanghai Oriental Scholar", "Shanghai Outstanding Academic Leader", "Pujiang Talent", "Shuguang Plan", and "Shanghai Outstanding Discipline Leader". He has won the first prize of the Shanghai Medical Science and Technology Award, the second prize of the Military Science and Technology Progress Award, the Shanghai "Yucai Award", and the "Youth May Fourth Medal", and has opened the door to future medicine with a high-spirited attitude.

Carry forward: See the original intention, see all living beings

Initially, Gao Lu's ideal was to become a "sword-wielding" clinical doctor, directly facing patients and working with them to overcome diseases, but the trajectory of fate unexpectedly took him away from his desired destination. The reason why he can continue to shine in the research of basic medical theory today is thanks to the people who guided him along the way, one of whom is his master's supervisor, Professor Sun Gang, deputy director of the Reproductive Medicine Center of Renji Hospital, Shanghai Jiaotong University.

▲Photo of Gao Lu (fourth from left in the back row) and his research group

"I was very disappointed when I didn't get the clinical medicine major in the postgraduate entrance examination. It was Professor Sun Gang who came to comfort me at the first time and gave me great strength." Gao Lu recounted this experience in detail, "Before, my understanding of basic research was a bit narrow, and it can even be said that there were some misunderstandings. Professor Sun was the first person to patiently analyze the relationship between clinical and basic research with me. His words will always be unforgettable to me. He said: 'There is no distinction between high and low in scientific research, but the ways of benefiting the people are different. The improvement of clinical technology can certainly save lives from the dying, but the development of basic theory can promote the continuous updating of clinical technology and even hope to open up new ways of healing, which is also immeasurable for the development of medicine.' At that time, I realized that there is no matter how to save the world. If you come, you should make the best of it. You should love what you do." Since then, Gao Lu's research career has ushered in a "new life".

The spiritual support that guided Gao Lu to work hard and persevere in the field of reproductive medicine is also mentioned in the article of Professor Carole Mendelson, a senior in the industry whom he deeply admired. In his fifth year of work, Gao Lu went to the University of Texas Southwestern Medical Center in the United States to carry out two years of academic work in order to broaden his scientific research horizons and follow the international frontier. His co-mentor was the person who added weight to this experience.

When I first met Professor Carol Mendelsohn, she was nearly 70 years old, but her vigorous spirit and enthusiasm for scientific research made it hard to tell that she was past the age of "retirement". Gao Lu praised the time of studying with her as "a very pure period of time", and her professional accumulation also helped Gao Lu to enter a new level in the research of reproductive medicine. Although the limited visiting period forced Gao Lu to return to China with gratitude, the two did not stop their cooperation. Until January 2023, the invention of Internet email continued to shorten the distance across the ocean. However, what Gao Lu did not expect was that all the news came to an abrupt end in March of the same year, and then came the sad news of the death of his predecessor. With amazement and regret, he learned through many inquiries that it turned out that Professor Carol Mendelsohn had cancer about 3 years ago, but she chose to deliberately block the news in order to continue to stick to the scientific career she loved until the last moment of her life, when the candle burned out and her enthusiasm was extinguished.

Gao Lu was shocked by this persistence and perseverance. As a medical researcher, he knew very well that the best way to respect and cherish the memory of these academic predecessors was to "continue" and "carry forward" their scientific spirit, to complete their unfinished work and reach their unreached realm. Therefore, he worked hard and soon received support from the National Key R&D Program. He turned his attention to the physiological role of maternal and fetal factors in maintaining pregnancy and the pathological role in pregnancy complications. He worked hard to clarify the role of fetal factors in coordinating fetal development and the initiation of labor, laying the groundwork for high-quality and safe childbirth and avoiding pathological pregnancy.

Innovation: Talk about production and education, and talk about safety

"Premature birth is one of the most common pathological pregnancies, accounting for 9% to 11% of all pregnancies. Every year, approximately 15 million premature babies are born worldwide, of which nearly 1.1 million die from premature birth, making it the leading cause of perinatal neonatal death." Gao Lu said that in order to achieve the expected goals of the national key research and development program, it is necessary to overcome the mechanism of human labor initiation - a research hotspot and difficult problem in global reproductive medicine for nearly 20 years.

▲Gao Lu participated in the marathon in Shanghai

"Maintenance of human pregnancy and initiation of labor is a continuous and dynamic process. During this process, there is a constant real-time interactive dialogue between the mother and the fetus. However, the role of fetal factors in labor has long been ignored." From the perspective of the fetus, Gao Lu led the team to start from the role of fetal factors in coordinating fetal development and the initiation of labor. By activating the SRC-1/2 double-gene knockout fetal mouse model and observing its individual size, weight and fetal lung size, it was found that not only was the body size of the experimental group generally smaller than that of wild-type mice, but the maturity of their fetal lung development was also low; at the same time, the release of pulmonary surfactant-associated protein SP-A and platelet-activating factor (PAF) by the mouse fetal lung was reduced, resulting in a delay in the initiation of labor. This discovery provided direct experimental evidence for the first time at home and abroad that fetal factors coordinate fetal lung function and the initiation of labor, and therefore received great attention and wide acclaim from peers at home and abroad.

Professor Sarah England, a famous American obstetrician and gynecologist, wrote a review, highly praising the important theoretical value of this work in revealing the mechanism of initiating human labor; Medical Daily, a popular medical science magazine in the United States, reported that this discovery "precisely found the exact cause of fetal labor for the first time... making it possible to prevent or delay the occurrence of premature birth" and "will have life-changing significance for the next generation of children and their families." The result "The influence of maternal and fetal internal and external factors on fetal development and pregnancy outcomes" based on this result won the first prize of the 2018 Shanghai Medical Science and Technology Award.

However, Gao Lu's team did not stop there. Through further research, they found that the expression of C/ebpα, C/ebpβ and 11-HSD1 in the fetal lungs of SRC-1/2 double-gene knockout mice was reduced, which would reduce the ability to activate glucocorticoids and inhibit the expression of ARG1, a key enzyme in arginine metabolism, leading to increased arginine content and decreased ornithine content. It can not only induce apoptosis of fetal lung epithelial cells and thus lead to abnormal fetal lung development, but also inhibit the contraction of uterine smooth muscle through paracrine pathways to interfere with the initiation of labor. This result provides further experimental evidence for the coordinated relationship between fetal development and the initiation of labor. Professor Xia Yang, director of the National Joint Research Center for Medical Metabolomics, commented that the latest research results of Gao Lu's team "revealed the metabolomics changes of fetal lung development in the middle and late stages of pregnancy, which has important theoretical significance for our in-depth understanding of the metabolic regulation mechanism of fetal lung development." Professor Chen Dongbao of the Department of Obstetrics and Gynecology at the University of California, Irvine, commented that this work "further enriched the signal theory of fetal-derived factors regulating the initiation of labor, and can also provide a theoretical basis for understanding the motivation for the initiation of labor from a new perspective and developing interventions for premature birth." In 2022, Gao Lu was invited to publish a review on maternal and fetal factors of premature birth in the basic research key issue of the Journal of Maternal Fetal Medicine. The number of readers of the article ranked among the top five in the magazine that year. In 2023, Gao Lu was also invited to give an oral report at the 70th International Conference on Reproductive Science Research held in Brisbane, Australia.

"Dopamine brings happiness, while endorphins bring a sense of accomplishment," said Gao Lu, a physiologist and marathon enthusiast. "Scientific research is like long-distance running. It may not bring us temporary pleasure, but through long-term self-discipline, the dual physical and mental efforts will bring us endorphin-like sense of accomplishment and happiness." As Gao Lu said, whether it is work or life, it is like a race with an unknown end. The guiding principle of "inheritance, development, collaboration, and innovation" is still hanging in the sight of the Physiology Teaching and Research Section of the Naval Medical University. The beautiful wish of "strengthening the army, revitalizing the people, eliminating diseases, and eugenics" is still deeply rooted in one's heart. Only with endless struggle with youth and passion can we explore new possibilities for human life and safeguard the great cause of human reproduction.

Expert Profile

Gao Lu, professor and doctoral supervisor, director of the Department of Physiology at the Naval Medical University, a national "Excellent Young Scientist", a Shanghai "Oriental Scholar" distinguished professor, an "Outstanding Academic Leader" in Shanghai, an executive director of the Chinese Physiological Society, and the incoming chairman of the Reproductive Science Professional Committee of the Chinese Physiological Society. Over the years, he has been mainly engaged in research related to reproductive physiology and developmental biology, with specific directions including labor initiation regulation and premature birth prevention and treatment, fetal organ development and function regulation, and physiological function adaptability under special environments. As the project leader, he has undertaken more than ten projects of various types, including the National Natural Science Foundation Key International Cooperation Project, the Excellent Young Scientist Project, the National Key R&D Program, and the Shanghai Municipal Education Commission's Major Scientific Research and Innovation Program. As the first author or corresponding author, he has published more than 30 Science Citation Index (SCI) papers, with the highest single-paper impact factor reaching 19.456; he has edited one textbook and participated in the editing of seven books.