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Sudhansu K Dey

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In the rat, two key reproductive phenomena—morula to blastocyst transformation, and implantation—are known to be affected by oestrogen/progesterone changes in the mother. Thus, experimentally imposed hormonal changes can prevent the transformation of morula to blastocyst (Dickmann, 1970, 1973) and delay and induce implantation (Nutting & Meyer, 1963; Mayer 1963). It has been axiomatic that the ovary is the source of oestrogen and progesterone necessary during the preimplantation period. The results of the present study suggest that the preimplantation embryo is an additional, perhaps indispensable, source of steroid hormones which influence the two phenomena mentioned.

Adult virgin female rats of the Holtzman strain, weighing 180 to 220 g, were mated with males of proven fertility. The morning of finding spermatozoa in the vagina was designated Day 1 of pregnancy. On Days 3, 4 and 5, rats were killed and the fertilized eggs were recovered according to the method described by Dickmann

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The activity pattern and functional significance of leucine aminopeptidase (LAP) have been studied in the testes of oestrogen-treated, cryptorchid and HCG-treated guinea-pigs. The enzyme was present only in the Leydig cells and showed marked fluctuations in its activity pattern, which correlated closely with alterations in the functional activities of the Leydig cells. Hyperfunctioning Leydig cells exhibited enhanced LAP activity, whereas hypofunctioning of these intertubular cells resulted in a diminution in the enzyme activity. The LAP activity in the intertubular Leydig cells may be regarded as a cytochemical marker enzyme in the assessment of Leydig cell function in the guinea-pig testes under varying experimental conditions.

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Jiyoung Hong, Sung Tae Kim, Susanne Tranguch, David F Smith and Sudhansu K Dey

FKBP52 is a member of the FK506-binding family of immunophilins and serves as a co-chaperone for steroid hormone nuclear receptors to govern appropriate hormone action in target tissues. Male mice missing Fkbp52 are infertile, and this infertility has been ascribed to compromised sensitivity of the anterior prostate, external genitalia, and other accessory sex organs to androgen. Here, we show additional defects contributing to infertility. We found that epididymal Fkbp52 −/− sperm are sparse often with aberrant morphology, and they have reduced fertilizing capacity. This phenotype, initially observed in null males on a C57BL/6/129 background, is also maintained on a CD1 background. Expression studies show that while FKBP52 and androgen receptor are co-expressed in similar cell types in the epididymis, FKBP52 is also present in epididymal sperm flagella. Collectively, our results suggest that reduced number and abnormal morphology contribute to compromised fertilizing capacity of Fkbp52 −/− sperm. This study is clinically relevant because unraveling the role of immunophilin signaling in male fertility will help identify new targets for male contraceptives and/or alleviate male infertility.

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Shizu Aikawa, Jia Yuan, Amanda Dewar, Xiaofei Sun and Sudhansu K Dey

Mammary glands are comprised of ducts and terminal lobules that form tree-like structures. Luminal epithelial cells in these lobules undergo differentiation into alveolar cells in pregnancy to support milk production. This study reveals that Scribble (SCRIB), a scaffold protein expressed in progesterone receptor (PGR)-positive cells, plays a critical role in mammary gland alveologenesis in mice. We conditionally deleted Scrib using a Pgr-Cre driver. PGR is heterogeneously expressed throughout the luminal epithelium. Scrib loss in mammary glands by Pgr-Cre (Scribf/fPgrCre/+) shows inefficient alveologenesis and terminal end bud (TEB)-like morphology during pregnancy, resulting in poor milk production and subsequent death of pups after delivery. The differentiation of PGR-positive epithelial cells into Elf5-expressing alveolar cells is defective in Scribf/fPgrCre/+ mice. These changes are reflected in reduced activation of JAK2 and PAK1, resulting in downregulation of pSTAT5, a critical transcriptional factor for alveologenesis. These results provide evidence that SCRIB impacts PGR-positive cell lineage during alveologenesis, which impacts milk production and the health of offspring.