Background: Obesity is a serious health concern among pregnant women. Maternal obesity can result from caloric surplus and increase the risk of mental health disorders, which includes peripartum depression. Peripartum depression negatively affects maternal behavior and threatens the mother and her child’s well-being. In mice, eating a high fat diet versus a control diet can negatively affect placental structure, function and maternal behavior. The link between obesity and peripartum depression is poorly understood. However, a potential link might be placental lactogen. Placental lactogen hormone is produced in pregnancy, but lower levels of production have been associated in some cases with maternal obesity and peripartum depression. Placental lactogen is a lactogenic hormone that binds to the prolactin receptor. Placental lactogen is also detected in the cerebrospinal fluid in humans, and therefore, it has the potential ability to modify neurophysiology. A neurobiological mechanism that has been implicated in depression is neurogenesis. Neural stem cell proliferation is an essential component of neurogenesis. Brain stem cell proliferation can be assessed by immunofluorescent labeling of proliferative cell markers; for example, bromodeoxyuridine (BrdU) and Ki67. Neurogenesis occurs in pregnancy at gestation day (GD) 7 in the subventricular zone of wild type CD-1 mice. Prolactin receptor signaling is a key mediator of maternal neurogenesis. Thus, a reduction in prolactin receptor signaling, which can occur due to a decrease in lactogen levels, might lead to reduced maternal neurogenesis and help explain an increased risk of developing peripartum depression. Such events can occur in an obese state which is promoted by high fat diet consumption. Hence, it was hypothesized that: i) cells expressing both proliferation markers, BrdU and Ki67, are present in the subventricular zone of mice with a CD-1 genetic background, consistent with neurogenesis; and ii) that high fat diet-induced obesity in these mice decreases maternal neurogenesis and is associated with reduced prolactin receptor signaling in the brain as reflected by downstream targets. Specifically, these targets include decreased expression of phosphorylated signal transducer and activator of transcription (STAT) 5 and/or phosphorylated mitogen- activated protein kinase (MAPK) levels. Methods: To test the hypothesis, a CD-1 based transgenic mouse line, CD-1[hGH/PL], was used. The CD-1[hGH/PL] mice contain the genetic background of wild type CD-1mice along with a transgene that encodes human placental lactogen. Mice were fed a high fat diet for four weeks before pregnancy to induce an obese state in pregnancy. The cell proliferation stage of neurogenesis was assessed by counting cells positive for markers of cell division (BrdU and Ki67) in the subventricular zone and subgranular zone at GD 7. Levels of prolactin receptor signaling were determined by measuring markers of activated prolactin receptor; specifically, phosphorylated STAT5 and phosphorylated MAPK. Results: Conditions for the independent and dual-immunofluoresent labeling of BrdU and Ki67 in formaldehyde-fixed frozen sections of the subventricular zone and subgranular zone of the mouse brain were established. In addition, a modified methodology for quantification of labeled cells in designated brain regions in three dimensions (X, Y and Z axes) was successfully applied. However, although detected, the number of BrdU and Ki67 positive cells in the subventricular zone and subgranular zone were unaffected by pregnancy as well as high fat diet versus regular chow diet in the CD-1[hGH/PL] mice at GD 7. Phosphorylated MAPK signaling was also unaffected by pregnancy and diet in the subventricular zone and subgranular zone. Immunological conditions for phosphorylated STAT5 staining could not be achieved. Conclusions: Evidence of proliferation and thus, adult neurogenesis was detected in the subventricular zone and subgranular zone of the female CD-1[hGH/PL] mouse brain, including during pregnancy. Under conditions where weight gain was observed, there was no effect of pregnancy or HFD on cell proliferation or lactogenic signaling at GD 7. Thus, the transgenic DNA fragment in CD-1[hGH/PL] mice may disrupt the effect of pregnancy on maternal neurogenesis described previously in wild type CD-1 mice at GD 7. This raises the possibility that products of the transgenic hGH/PL DNA can influence neurogenesis in the maternal mouse brain. This includes the possible influence of additional lactogenic activity as a result of human placental lactogen production in early pregnancy, on events or timing of those events in the maternal system. Specifically, human placental lactogen might interfere with endogenous prolactin activity and/or result in increased insulin secretion and reduced glucose availability to the brain in the first week of pregnancy. Alternatively, the four-week high fat diet may not have been sufficient to create a state of sufficient corpulence or obesity as seen in humans to result in sufficient changes to lactogen levels and/or prolactin receptor signaling to see an effect. Future studies would investigate the important role of the human growth hormone/placental lactogen transgenic DNA product(s) in influencing pregnancy-stimulated neurogenesis along with an elaborate characterization of the four-week high fat diet obesity model employed in this project. These mechanistic studies should be accompanied by an investigation of maternal behavior outcomes that together may provide insight into the role of placental lactogen in pregnancy and potentially in the etiology and management of peripartum depression.