Research

Overview:

In the last 50 years, sperm counts in men have declined by over 50% demonstrating a male fertility crisis. Moreover, reproductive failure is a major constraint to the efficiency of livestock production. The broad focus of my research program is elucidating the biology of male reproduction and endocrinology. More specifically, we study the development and function of the mammalian testis, especially Leydig cells which produce steroid hormones that are critical for reproductive success. In my lab, we are investigating physiological, cellular, and molecular factors involved in Leydig function using murine and porcine models. A deeper understanding of the factors that affect Leydig cell function is essential to the development of novel therapies or intervention strategies to maximize fertility in both animals and humans.

Current Research Topics:

(1) Lactocrine programming of testis development

Conception rate, farrowing rate, and litter size govern the productivity of pork production. Due to the nearly exclusive use of artificial insemination in the swine industry, a single boar affects the fertility of thousands of females. Thus, the boar has the greatest cumulative impact on reproductive outcomes and drives genetic progress in the herd. Yet boar fertility is often overlooked, representing an untapped avenue to rapidly improve swine production efficiency. New evidence demonstrates that nursing promotes the growth and development of the swine testis leading to greater reproductive function in the boar. Our objective is to identify early nutritional interventions that improve reproductive development and fertility of boars. In addition, we are also working to identify the specific components of milk that confer these benefits. This knowledge is critical because extensive testicular growth and development occurs during the neonatal period, yet replacement boars may not have adequate colostrum access due to growing litter sizes and climate change. Simple interventions (e.g., targeted supplementation) could be rapidly implemented to improve testis function in neonatal boars currently being developed, leading to advancements in both swine fertility and genetic progress which will enhance the profitability of pork production. In addition, this research has biomedical applications because nursed human infants have improved testis growth compared to formula-fed controls but only 25% of babies exclusively receive breast milk through 6 months of age. Interventions (e.g., targeted supplementation) could improve nutrition for 1.9 million male infants annually leading to population-level fertility and health benefits for men.

(2) Effects of in utero heat stress on testis development and function

Given the growing population and limited natural resources, enhancing the efficiency of food production is critical. Reproductive failure is a major limitation to swine production. Notably, summer heat stress reduces fertility in the male pig by reducing spermatogenesis and sperm motility as well as increasing sperm abnormalities. Due to climate change, heat stress is expected to be a major threat to the sustainability of livestock production. Notably, heat stress is also a rising concern for humans, especially those from disadvantaged backgrounds or developing countries. While the effects of heat stress on male fertility have been well documented, the impact of prenatal heat stress is less clear. Stress during gestation increases plasma cortisol concentrations within the dam, which impairs fetal steroidogenesis and gonadogenesis. Given that over 6 million pregnant sows experience summer heat stress, the effect of prenatal heat stress on testis development demands further evaluation. Therefore, Dr. Desaulniers’ early work at the University of Missouri-Columbia sought to examine the effects of prenatal heat stress on male fertility in a mouse model. Mild maternal heat stress demasculinized males for life. These effects were likely due to reduced fetal androgen production as indicated by a reduced anogenital distance in the male mice exposed to prenatal heat stress. Notably, the effects of prenatal heat stress were fully mitigated by concurrent maternal supplementation of an antipyretic herb (Artemisia absinthium), demonstrating a potential dietary agent to protect fetal testes from gestational heat stress. In pigs, we have recently discovered that prenatal heat stress impairs testis development and alters abundance of >600 proteins within the testicular proteome including proteins important for steroid hormone production (e.g., CYP19). Therefore, we are currently investigating the biological consequences of prenatal heat stress on boar fertility. The successful outcome of this work will result in new mechanistic knowledge about how in utero heat stress impacts reproductive physiology of boars on the endocrine, cellular, molecular, & whole-animal level. We will apply this new insight to explore practical approaches (e.g., genomic selection for heat tolerance) to mitigate in utero heat stress & develop boars with greater fertility.

(3) Role of GnRH-II and its receptor in testis function of pigs

The second mammalian form of GnRH (GnRH-II) and its cognate receptor (GnRHR-II) are produced in only one livestock species, the pig. Dr. Desaulniers’ graduate work demonstrated that the physiological interaction of GnRH-II with its receptor does not stimulate gonadotropin secretion in the pig. Instead, both are abundantly produced within the testis, where GnRH-II immunolocalizes to seminiferous tubules, and GnRHR-II is present on the plasma membrane on Leydig cells. Her M.S. work revealed that GnRH-II elicited testosterone secretion both in vivo and ex vivo without the classical androgen stimulator, luteinizing hormone. These data suggest that GnRH-II and GnRHR-II are local regulators of steroidogenesis within swine testes; however, the function and biological mechanisms of GnRH-II mediated steroidogenesis remained unclear. Utilizing genetically engineered pigs produced in the laboratory of Dr. Brett White, Dr. Desaulniers’ USDA-funded doctoral work focused on: 1) evaluating the physiological consequences of GnRHR-II knockdown within the porcine testis; and 2) determining the molecular mechanisms that regulate GnRH-II mediated steroidogenesis within porcine Leydig cells. Notably, disruption of GnRHR-II expression within the porcine testis ablated synthesis of 10 gonadal steroids and reduced semen quality. Thus, GnRH-II and its receptor are critical regulators of porcine Leydig cell function and represent novel molecular targets to improve male fertility.