Sprague Dawley®: The workhorse of reproductive endocrinology research - part 1

The history of advancing basic research
Infertility has profound psychological and social effects on millions of people. Despite considerable research, there remain many unanswered questions as to the potential causes of infertility or impaired fecundity. What if the humble rat could help unlock the puzzle of infertility? The Sprague Dawley^® rat is no ordinary model. These rats have proven to be extremely helpful in reproductive endocrinology research.

The first Sprague Dawley^® rat colony began in 1925, when Robert Dawley developed a vigorous rat with a good temperament and high rates of lactation. These rats were eventually used to study contraceptives. In 1980, the original colony was acquired by Harlan (now Inotiv). These albino rats are now used widely in medical and psychological research.

Both males and females become sexually mature at about 65 days old and can breed throughout the year. Rats have a very short gestation period of 22 days; pups can be weaned around three weeks of age and females can begin cycling again two to four days after weaning.

Sprague Dawley® rat colonies are now located worldwide and are maintained by numerous research and commercial entities. Interestingly, rats from different vendor colonies display divergent responses to experimental situations, stressing the need to identify colony-specific differences in endocrine and immune responses in Sprague Dawley^® rats if using multiple suppliers.

Studying the molecular underpinnings of reproductive endocrinology research
Inotiv-supplied Hsd:Sprague Dawley^® SD^® rats have recently supported a variety of reproductive endocrinology studies. Nilsson et al. investigated primordial follicle transition in the rat ovary to better understand the roles of endogenous bone morphogenetic protein (BMP) inhibitors Gremlin 1 (GREM1) and GREM2. The control of primordial to primary follicle transition is crucial to successful reproduction. If the pool of primordial follicles that contain a woman’s oocytes is depleted early in life, women can enter menopause in their twenties or thirties.

Researchers studied this process by removing the ovaries from four-day old female rats and culturing them. The ovaries treated with GREM1 or GREM2 yielded negligible numbers of differentially expressed genes, leaving the authors to believe that the immediate effects of GREM1 or GREM2 appear to be at the level of protein-protein interactions, rather than direct actions on the cells. This improved the field’s understanding of primordial to primary follicle transition and lead to better tools for treating reproductive diseases.

Reproductive aging studied by Walker et al., focused on perinatal exposure to estrogenic endocrine disruptors (EEDs), exogenous, man-made chemicals that can alter the functions of the endocrine system. Using Hsd:Sprague Dawley^® SD^® rats, Walker’s team exposed an endocrine disruptor to pregnant female rats at gestational days 16 and 18.

Female offspring of the exposed rats underwent a different reproductive aging process than their control counterparts but there was no effect in males, highlighting the possibility of sexually dimorphic effects, including an altered transition to reproductive aging in female rats. The investigators also identified potential biomarkers that may provide a subject for future experiments on reproductive senescence.

Many other reproductive and endocrinology challenges have been studied with the robust model of Hsd:Sprague Dawley^® SD^® rats. Learn more about the recent research in part 2 of this blog series.

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